<div id="pf1" class="pf w0 h0" data-page-no="1"><div class="pc pc1 w0 h0"><img class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg1.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">1</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x4 h5 y7 ff3 fs1 fc0 sc0 lsc ws5">FUND<span class="_3 blank"></span>A<span class="_1 blank"> </span>MENT<span class="_3 blank"></span>OS+D<span class="_1 blank"> </span>E+</div><div class="t m1 x5 h5 y8 ff3 fs1 fc0 sc0 lsd ws6">NUTRIÇÃ<span class="_0 blank"></span>O+E+MET<span class="_4 blank"></span>ABOLISMO+</div><div class="t m1 x6 h6 y9 ff3 fs2 fc0 sc0 lse ws7">Lisboa</div><div class="t m1 x7 h7 ya ff3 fs3 fc0 sc0 lsf ws8">24+de+Setembro+de+2016</div><div class="t m1 x8 h8 yb ff3 fs4 fc0 sc0 ls10 ws9">Pe d ro +<span class="_5 blank"> </span>B a st o s</div></div><div class="c x3 yc w2 h4"><div class="t m1 x9 h9 yd ff4 fs5 fc0 sc0 ls0">P<span class="fs6 ls11 wsa">ROTEÍ<span class="_1 blank"> </span>NA</span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf2" class="pf w0 h0" data-page-no="2"><div class="pc pc2 w0 h0"><img class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg2.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">2</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 xa ha ye ff4 fs7 fc1 sc0 ls1 wsb">COMPOSIÇÃO QUÍMICA NORMAL DE UM HO<span class="_1 blank"> </span>MEM (70 Kg)</div><div class="t m1 xb hb yf ff4 fs8 fc2 sc0 ls15 wsc">Kg <span class="ls1">%</span></div><div class="t m2 xc hc y10 ff2 fs9 fc0 sc1 ls16 wsd">Pr<span class="_0 blank"></span>oteína <span class="ls17 wse">12 17,0</span></div><div class="t m1 xd hd y11 ff2 fs7 fc0 sc0 ls18 wsf">Lípidos <span class="ls12 ws10">9,7 13,8</span></div><div class="t m1 xe hd y12 ff2 fs7 fc0 sc0 ls13 ws11">CHO <span class="ls14">1<span class="ls12 ws12">1,5</span></span></div><div class="t m1 xf hd y13 ff2 fs7 fc0 sc0 ls19 ws13">Água <span class="ls12 ws14">43,1 61,6</span></div><div class="t m1 x10 hd y14 ff2 fs7 fc0 sc0 ls1a ws15">Minerais <span class="ls12 ws16">4,2 6,1</span></div><div class="t m1 x11 he y15 ff5 fsa fc3 sc0 ls1b wsb">Harper<span class="_0 blank"></span>, 1990</div></div><div class="c x3 yc w2 h4"><div class="t m1 x12 hf y16 ff4 fs1 fc0 sc0 ls1 ws17">P<span class="fsb ls1c ws18">ÉPTIDO</span>/P<span class="fsb ls1d ws19">ROTEÍNA</span></div><div class="t m1 x13 h10 y17 ff2 fsc fc3 sc0 ls1e ws1a">Newsholme <span class="ls1f wsb">E, <span class="ls20 ws1b">Leech </span><span class="ls21">A. <span class="ls22 ws1c">Functional <span class="ls23 ws1d">Biochemistry <span class="ls24 ws1e">in </span></span></span></span></span><span class="ws1f">Health <span class="ls25 ws20">and </span><span class="ws21">Disease<span class="ls26 wsb">. John </span></span><span class="ls27">Wiley <span class="ls28 wsb">& <span class="_0 blank"></span>Sons; 2011<span class="ls26">. </span></span></span></span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf3" class="pf w0 h0" data-page-no="3"><div class="pc pc3 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg3.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">3</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y18 w3 h11"><div class="t m3 xa h12 y19 ff6 fsd fc4 sc0 ls31 wsb">associated <span class="_1 blank"> </span>polypeptide <span class="_5 blank"> </span>chains, <span class="_1 blank"> </span>called <span class="_5 blank"> </span>subunits.</div><div class="t m3 xa h12 y1a ff6 fsd fc4 sc0 ls31 wsb">Simple <span class="_1 blank"> </span>proteins <span class="_5 blank"> </span>yield <span class="_1 blank"> </span>only <span class="_5 blank"> </span>amino <span class="_1 blank"> </span>acids <span class="_5 blank"> </span>on</div><div class="t m3 xa h12 y1b ff6 fsd fc4 sc0 ls31 wsb">hydrolysis; <span class="_1 blank"> </span>conjugated <span class="_5 blank"> </span>proteins <span class="_1 blank"> </span>contain <span class="_5 blank"> </span>in</div><div class="t m3 xa h12 y1c ff6 fsd fc4 sc0 ls31 wsb">addition <span class="_1 blank"> </span>some <span class="_5 blank"> </span>other <span class="_1 blank"> </span>component, <span class="_5 blank"> </span>such <span class="_1 blank"> </span>as <span class="_5 blank"> </span>a</div><div class="t m3 xa h12 y1d ff6 fsd fc4 sc0 ls31 wsb">metal <span class="_1 blank"> </span>or <span class="_5 blank"> </span>organic <span class="_1 blank"> </span>prosthetic <span class="_5 blank"> </span>group.</div><div class="t m3 x14 h12 y1e ff7 fse fc5 sc0 ls29">\u25a0<span class="ff6 fsd fc4 ls31 wsb">The <span class="_1 blank"> </span>sequence <span class="_5 blank"> </span>of <span class="_1 blank"> </span>amino <span class="_5 blank"> </span>acids <span class="_1 blank"> </span>in <span class="_5 blank"> </span>a <span class="_5 blank"> </span>protein <span class="_1 blank"> </span>is</span></div><div class="t m3 xa h12 y1f ff6 fsd fc4 sc0 ls31 wsb">characteristic <span class="_1 blank"> </span>of <span class="_5 blank"> </span>that <span class="_1 blank"> </span>protein <span class="_5 blank"> </span>and <span class="_1 blank"> </span>is <span class="_5 blank"> </span>called <span class="_5 blank"> </span>its</div><div class="t m3 xa h12 y20 ff6 fsd fc4 sc0 ls31 wsb">primary <span class="_1 blank"> </span>structure. <span class="_5 blank"> </span>This <span class="_1 blank"> </span>is <span class="_5 blank"> </span>one <span class="_1 blank"> </span>of <span class="_5 blank"> </span>four <span class="_5 blank"> </span>generally</div><div class="t m3 xa h12 y21 ff6 fsd fc4 sc0 ls31 wsb">recognized <span class="_1 blank"> </span>levels <span class="_5 blank"> </span>of <span class="_1 blank"> </span>protein <span class="_5 blank"> </span>structure.</div><div class="t m3 x15 h13 y22 ff8 fsf fc6 sc0 ls32 wsb">3.3 W<span class="_0 blank"></span>orking <span class="_5 blank"> </span>with <span class="_5 blank"> </span>Proteins</div><div class="t m3 x15 h12 y23 ff6 fsd fc4 sc0 ls31 wsb">Our <span class="_0 blank"></span>understanding <span class="_0 blank"></span>of <span class="_3 blank"></span>protein structure <span class="_3 blank"></span>and function <span class="_3 blank"></span>has</div><div class="t m3 x15 h12 y24 ff6 fsd fc4 sc0 ls31 wsb">been <span class="_0 blank"></span>derived <span class="_3 blank"></span>from <span class="_0 blank"></span>the <span class="_3 blank"></span>study <span class="_0 blank"></span>of <span class="_0 blank"></span>many <span class="_3 blank"></span>individual <span class="_0 blank"></span>proteins.</div><div class="t m3 x15 h12 y25 ff6 fsd fc4 sc0 ls33 wsb">To<span class="_5 blank"> </span> <span class="_1 blank"> </span>s<span class="_5 blank"> </span>t<span class="_1 blank"> </span>u<span class="_5 blank"> </span>d<span class="_5 blank"> </span>y<span class="_5 blank"> </span> <span class="_1 blank"> </span>a<span class="_5 blank"> </span> <span class="_1 blank"> </span>p<span class="_5 blank"> </span>r<span class="_5 blank"> </span>o<span class="_5 blank"> </span>t<span class="_1 blank"> </span>e<span class="_5 blank"> </span>i<span class="_5 blank"> </span>n<span class="_1 blank"> </span> <span class="_5 blank"> </span>i<span class="_5 blank"> </span>n<span class="_1 blank"> </span> <span class="_5 blank"> </span>d<span class="_5 blank"> </span>e<span class="_1 blank"> </span>t<span class="_5 blank"> </span>a<span class="_5 blank"> </span>i<span class="_5 blank"> </span>l<span class="_1 blank"> </span>,<span class="_5 blank"> </span> <span class="_1 blank"> </span>t<span class="_5 blank"> </span>h<span class="_5 blank"> </span>e<span class="_5 blank"> </span> <span class="_1 blank"> </span>r<span class="_5 blank"> </span>e<span class="_5 blank"> </span>s<span class="_1 blank"> </span>e<span class="_5 blank"> </span>a<span class="_5 blank"> </span>r<span class="_5 blank"> </span>c<span class="_1 blank"> </span>h<span class="_5 blank"> </span>e<span class="_5 blank"> </span>r<span class="_1 blank"> </span> <span class="_5 blank"> </span>m<span class="_5 blank"> </span>u<span class="_1 blank"> </span>s<span class="_5 blank"> </span>t<span class="_5 blank"> </span> <span class="_1 blank"> </span>b<span class="_5 blank"> </span>e<span class="_5 blank"> </span> <span class="_1 blank"> </span>a<span class="_5 blank"> </span>b<span class="_5 blank"> </span>l<span class="_1 blank"> </span>e</div><div class="t m3 x15 h12 y26 ff6 fsd fc4 sc0 ls31 wsb">to <span class="_6 blank"> </span>separate <span class="_6 blank"> </span>it <span class="_6 blank"> </span>from <span class="_6 blank"> </span>other <span class="_6 blank"> </span>proteins <span class="_6 blank"> </span>and <span class="_6 blank"> </span>must <span class="_6 blank"> </span>have <span class="_6 blank"> </span>the</div><div class="t m3 x15 h12 y27 ff6 fsd fc4 sc0 ls31 wsb">techniques <span class="_7 blank"> </span>to <span class="_7 blank"> </span>determine <span class="_7 blank"> </span>its <span class="_7 blank"> </span>properties. <span class="_7 blank"> </span>The <span class="_7 blank"> </span>necessary</div><div class="t m3 x15 h12 y28 ff6 fsd fc4 sc0 ls31 wsb">methods <span class="_7 blank"> </span>come <span class="_6 blank"> </span>from <span class="_7 blank"> </span>protein <span class="_6 blank"> </span>chemistry<span class="_0 blank"></span>, <span class="_7 blank"> </span>a <span class="_7 blank"> </span>discipline <span class="_6 blank"> </span>as</div><div class="t m3 x15 h12 y29 ff6 fsd fc4 sc0 ls31 wsb">old <span class="_1 blank"> </span>as <span class="_1 blank"> </span>biochemistry <span class="_1 blank"> </span>itself <span class="_1 blank"> </span>and <span class="_1 blank"> </span>one <span class="_1 blank"> </span>that <span class="_1 blank"> </span>retains <span class="_1 blank"> </span>a <span class="_1 blank"> </span>central</div><div class="t m3 x15 h12 y2a ff6 fsd fc4 sc0 ls31 wsb">position <span class="_1 blank"> </span>in <span class="_5 blank"> </span>biochemical <span class="_1 blank"> </span>research.</div><div class="t m3 x15 h14 y2b ff8 fs10 fc5 sc0 ls34 wsb">Proteins <span class="_5 blank"> </span>Can <span class="_1 blank"> </span>Be <span class="_5 blank"> </span>Separated <span class="_1 blank"> </span>and <span class="_5 blank"> </span>Purified</div><div class="t m3 x15 h12 y2c ff6 fsd fc4 sc0 ls31 wsb">A <span class="_1 blank"> </span>pure <span class="_5 blank"> </span>preparation <span class="_1 blank"> </span>is <span class="_5 blank"> </span>essential <span class="_1 blank"> </span>before <span class="_5 blank"> </span>a <span class="_1 blank"> </span>protein\u2019<span class="_0 blank"></span>s <span class="_1 blank"> </span>prop-</div><div class="t m3 x15 h12 y2d ff6 fsd fc4 sc0 ls31 wsb">erties and activities <span class="_1 blank"> </span>can be <span class="_1 blank"> </span>determined. Given that <span class="_1 blank"> </span>cells</div><div class="t m3 x15 h12 y2e ff6 fsd fc4 sc0 ls31 wsb">contain <span class="_6 blank"> </span>thousands <span class="_6 blank"> </span>of <span class="_8 blank"> </span>different <span class="_6 blank"> </span>kinds <span class="_6 blank"> </span>of <span class="_8 blank"> </span>proteins, <span class="_6 blank"> </span>how</div><div class="t m3 x15 h12 y2f ff6 fsd fc4 sc0 ls31 wsb">can <span class="_0 blank"></span>one <span class="_3 blank"></span>protein be <span class="_3 blank"></span>purified? Methods <span class="_3 blank"></span>for separating <span class="_3 blank"></span>pro-</div><div class="t m3 x15 h12 y30 ff6 fsd fc4 sc0 ls31 wsb">teins <span class="_7 blank"> </span>take <span class="_7 blank"> </span>advantage <span class="_6 blank"> </span>of <span class="_7 blank"> </span>properties <span class="_6 blank"> </span>that <span class="_7 blank"> </span>vary <span class="_6 blank"> </span>from <span class="_7 blank"> </span>one</div><div class="t m3 x15 h12 y31 ff6 fsd fc4 sc0 ls31 wsb">protein <span class="_1 blank"> </span>to <span class="_5 blank"> </span>the <span class="_1 blank"> </span>next, <span class="_1 blank"> </span>including <span class="_5 blank"> </span>size, <span class="_1 blank"> </span>charge, <span class="_5 blank"> </span>and <span class="_1 blank"> </span>binding</div><div class="t m3 x15 h12 y32 ff6 fsd fc4 sc0 ls31">properties.</div><div class="t m3 x14 h12 y33 ff6 fsd fc4 sc0 ls31 wsb">The <span class="_6 blank"> </span>source <span class="_7 blank"> </span>of <span class="_6 blank"> </span>a <span class="_6 blank"> </span>protein <span class="_6 blank"> </span>is <span class="_6 blank"> </span>generally <span class="_6 blank"> </span>tissue <span class="_6 blank"> </span>or <span class="_6 blank"> </span>mi-</div><div class="t m3 x15 h12 y34 ff6 fsd fc4 sc0 ls31 wsb">crobial <span class="_7 blank"> </span>cells. <span class="_7 blank"> </span>The <span class="_6 blank"> </span>first <span class="_7 blank"> </span>step <span class="_6 blank"> </span>in <span class="_7 blank"> </span>any <span class="_7 blank"> </span>protein <span class="_6 blank"> </span>purification</div><div class="t m3 x15 h12 y35 ff6 fsd fc4 sc0 ls31 wsb">procedure <span class="_5 blank"> </span>is <span class="_7 blank"> </span>to <span class="_7 blank"> </span>break <span class="_7 blank"> </span>open <span class="_7 blank"> </span>these <span class="_7 blank"> </span>cells, <span class="_5 blank"> </span>releasing <span class="_7 blank"> </span>their</div><div class="t m3 x15 h12 y36 ff6 fsd fc4 sc0 ls35 wsb">proteins <span class="_1 blank"> </span>into <span class="_1 blank"> </span>a <span class="_1 blank"> </span>solution <span class="_1 blank"> </span>called <span class="_1 blank"> </span>a <span class="_5 blank"> </span><span class="ff9 ls31">crude <span class="_1 blank"> </span>extract. <span class="ff6">If <span class="_1 blank"> </span>nec-</span></span></div><div class="t m3 x15 h12 y37 ff6 fsd fc4 sc0 ls31 wsb">essary<span class="_3 blank"></span>, <span class="_8 blank"> </span>differential <span class="_6 blank"> </span>centrifugation <span class="_6 blank"> </span>can <span class="_8 blank"> </span>be <span class="_6 blank"> </span>used <span class="_6 blank"> </span>to <span class="_8 blank"> </span>pre-</div><div class="t m3 x16 h12 y19 ff6 fsd fc4 sc0 ls31 wsb">pare <span class="_9 blank"> </span>subcellular <span class="_9 blank"> </span>fractions <span class="_9 blank"> </span>or <span class="_9 blank"> </span>to <span class="_9 blank"> </span>isolate <span class="_9 blank"> </span>specific <span class="_9 blank"> </span>or-</div><div class="t m3 x16 h12 y1a ff6 fsd fc4 sc0 ls31 wsb">ganelles <span class="_1 blank"> </span>(see <span class="_5 blank"> </span>Fig. <span class="_1 blank"> </span>1\u2013<span class="_5 blank"> </span>8).</div><div class="t m3 x17 h12 y1b ff6 fsd fc4 sc0 ls31 wsb">Once <span class="_1 blank"> </span>the <span class="_5 blank"> </span>extract <span class="_1 blank"> </span>or <span class="_5 blank"> </span>organelle <span class="_1 blank"> </span>preparation <span class="_5 blank"> </span>is <span class="_1 blank"> </span>ready<span class="_0 blank"></span>,</div><div class="t m3 x16 h12 y1c ff6 fsd fc4 sc0 ls31 wsb">various methods <span class="_1 blank"> </span>are available <span class="_1 blank"> </span>for purifying <span class="_1 blank"> </span>one <span class="_1 blank"> </span>or more</div><div class="t m3 x16 h12 y1d ff6 fsd fc4 sc0 ls31 wsb">of <span class="_0 blank"></span>the <span class="_3 blank"></span>proteins <span class="_0 blank"></span>it <span class="_0 blank"></span>contains. <span class="_3 blank"></span>Commonly<span class="_0 blank"></span>, <span class="_3 blank"></span>the <span class="_0 blank"></span>extract <span class="_0 blank"></span>is <span class="_3 blank"></span>sub-</div><div class="t m3 x16 h12 y38 ff6 fsd fc4 sc0 ls31 wsb">jected to <span class="_1 blank"> </span>treatments that <span class="_1 blank"> </span>separate the <span class="_1 blank"> </span>proteins into dif-</div><div class="t m3 x16 h12 y39 ff6 fsd fc4 sc0 ls31 wsb">ferent <span class="_8 blank"> </span>fractions based <span class="_8 blank"> </span>on <span class="_8 blank"> </span>a property <span class="_8 blank"> </span>such <span class="_8 blank"> </span>as size <span class="_8 blank"> </span>or</div><div class="t m3 x16 h12 y3a ff6 fsd fc4 sc0 ls31 wsb">charge, <span class="_7 blank"> </span>a <span class="_7 blank"> </span>process <span class="_6 blank"> </span>referred <span class="_7 blank"> </span>to <span class="_7 blank"> </span>as <span class="_6 blank"> </span><span class="ff9 ls35 ws22">fractionation. </span>Early</div><div class="t m3 x16 h12 y3b ff6 fsd fc4 sc0 ls31 wsb">fractionation steps in <span class="_0 blank"></span>a purification <span class="_0 blank"></span>utilize differences <span class="_0 blank"></span>in</div><div class="t m3 x16 h12 y3c ff6 fsd fc4 sc0 ls31 wsb">protein <span class="_6 blank"> </span>solubility<span class="_3 blank"></span>, <span class="_8 blank"> </span>which <span class="_7 blank"> </span>is <span class="_8 blank"> </span>a <span class="_7 blank"> </span>complex <span class="_8 blank"> </span>function <span class="_6 blank"> </span>of <span class="_6 blank"> </span>pH,</div><div class="t m3 x16 h12 y3d ff6 fsd fc4 sc0 ls31 wsb">temperature, <span class="_1 blank"> </span>salt concentration, <span class="_1 blank"> </span>and <span class="_1 blank"> </span>other <span class="_1 blank"> </span>factors. <span class="_1 blank"> </span>The</div><div class="t m3 x16 h12 y3e ff6 fsd fc4 sc0 ls31 wsb">solubility <span class="_6 blank"> </span>of <span class="_6 blank"> </span>proteins <span class="_6 blank"> </span>is <span class="_6 blank"> </span>generally <span class="_6 blank"> </span>lowered <span class="_8 blank"> </span>at <span class="_7 blank"> </span>high <span class="_8 blank"> </span>salt</div><div class="t m3 x16 h12 y3f ff6 fsd fc4 sc0 ls31 wsb">concentrations, <span class="_1 blank"> </span>an <span class="_1 blank"> </span>effect <span class="_1 blank"> </span>called <span class="_1 blank"> </span>\u201csalting <span class="_1 blank"> </span>out.\u201d <span class="_1 blank"> </span>The <span class="_1 blank"> </span>addi-</div><div class="t m3 x16 h12 y40 ff6 fsd fc4 sc0 ls31 wsb">tion <span class="_7 blank"> </span>of <span class="_6 blank"> </span>a <span class="_6 blank"> </span>salt <span class="_6 blank"> </span>in <span class="_6 blank"> </span>the <span class="_6 blank"> </span>right <span class="_7 blank"> </span>amount <span class="_6 blank"> </span>can <span class="_6 blank"> </span>selectively <span class="_6 blank"> </span>pre-</div><div class="t m3 x16 h12 y41 ff6 fsd fc4 sc0 ls31 wsb">cipitate <span class="_1 blank"> </span>some <span class="_1 blank"> </span>proteins, <span class="_1 blank"> </span>while <span class="_1 blank"> </span>others <span class="_1 blank"> </span>remain <span class="_5 blank"> </span>in <span class="_1 blank"> </span>solution.</div><div class="t m3 x16 h12 y42 ff6 fsd fc4 sc0 ls31 wsb">Ammonium <span class="_7 blank"> </span>sulfate <span class="_7 blank"> </span>((NH</div><div class="t m4 x18 h15 y43 ff6 fs11 fc4 sc0 ls1">4</div><div class="t m3 x19 h12 y42 ff6 fsd fc4 sc0 ls1">)</div><div class="t m4 x1a h15 y43 ff6 fs11 fc4 sc0 ls1">2</div><div class="t m3 x1b h12 y42 ff6 fsd fc4 sc0 ls35">SO</div><div class="t m4 x1c h15 y43 ff6 fs11 fc4 sc0 ls1">4</div><div class="t m3 x1d h12 y42 ff6 fsd fc4 sc0 ls35 wsb">) <span class="_7 blank"> </span>is <span class="_7 blank"> </span>often <span class="_7 blank"> </span>used <span class="_7 blank"> </span>for <span class="_7 blank"> </span>this</div><div class="t m3 x16 h12 y44 ff6 fsd fc4 sc0 ls31 wsb">purpose <span class="_1 blank"> </span>because <span class="_5 blank"> </span>of <span class="_1 blank"> </span>its <span class="_5 blank"> </span>high <span class="_1 blank"> </span>solubility <span class="_5 blank"> </span>in <span class="_5 blank"> </span>water<span class="_3 blank"></span>.</div><div class="t m3 x17 h12 y45 ff6 fsd fc4 sc0 ls31 wsb">A <span class="_5 blank"> </span>solution <span class="_7 blank"> </span>containing <span class="_7 blank"> </span>the <span class="_7 blank"> </span>protein <span class="_7 blank"> </span>of <span class="_5 blank"> </span>interest <span class="_7 blank"> </span>often</div><div class="t m3 x16 h12 y46 ff6 fsd fc4 sc0 ls31 wsb">must <span class="_5 blank"> </span>be <span class="_5 blank"> </span>further <span class="_1 blank"> </span>altered <span class="_5 blank"> </span>before <span class="_5 blank"> </span>subsequent <span class="_5 blank"> </span>purification</div><div class="t m3 x16 h12 y47 ff6 fsd fc4 sc0 ls31 wsb">steps are possible. <span class="_0 blank"></span>For example, <span class="_0 blank"></span><span class="ff9 ls35 ws23">dialysis <span class="ff6 ls31 wsb">is a <span class="_0 blank"></span>procedure</span></span></div><div class="t m3 x16 h12 y48 ff6 fsd fc4 sc0 ls31 wsb">that <span class="_5 blank"> </span>separates <span class="_5 blank"> </span>proteins <span class="_5 blank"> </span>from <span class="_5 blank"> </span>solvents <span class="_5 blank"> </span>by <span class="_5 blank"> </span>taking <span class="_5 blank"> </span>advan-</div><div class="t m3 x16 h12 y49 ff6 fsd fc4 sc0 ls31 wsb">tage <span class="_7 blank"> </span>of <span class="_7 blank"> </span>the <span class="_6 blank"> </span>proteins\u2019 <span class="_7 blank"> </span>larger <span class="_7 blank"> </span>size. <span class="_7 blank"> </span>The <span class="_6 blank"> </span>partially <span class="_7 blank"> </span>purified</div><div class="t m3 x16 h12 y4a ff6 fsd fc4 sc0 ls31 wsb">extract <span class="_7 blank"> </span>is <span class="_7 blank"> </span>placed <span class="_7 blank"> </span>in <span class="_7 blank"> </span>a <span class="_6 blank"> </span>bag <span class="_7 blank"> </span>or <span class="_7 blank"> </span>tube <span class="_7 blank"> </span>made <span class="_7 blank"> </span>of <span class="_6 blank"> </span>a <span class="_7 blank"> </span>semiper-</div><div class="t m3 x16 h12 y4b ff6 fsd fc4 sc0 ls31 wsb">meable <span class="_5 blank"> </span>membrane. <span class="_7 blank"> </span>When <span class="_7 blank"> </span>this <span class="_5 blank"> </span>is <span class="_7 blank"> </span>suspended <span class="_7 blank"> </span>in <span class="_5 blank"> </span>a <span class="_7 blank"> </span>much</div><div class="t m3 x16 h12 y2c ff6 fsd fc4 sc0 ls31 wsb">larger <span class="_5 blank"> </span>volume <span class="_5 blank"> </span>of <span class="_5 blank"> </span>buffered <span class="_5 blank"> </span>solution <span class="_5 blank"> </span>of <span class="_7 blank"> </span>appropriate <span class="_5 blank"> </span>ionic</div><div class="t m3 x16 h12 y2d ff6 fsd fc4 sc0 ls31 wsb">strength, the membrane <span class="_0 blank"></span>allows the exchange of <span class="_0 blank"></span>salt and</div><div class="t m3 x16 h12 y2e ff6 fsd fc4 sc0 ls31 wsb">buffer <span class="_1 blank"> </span>but <span class="_1 blank"> </span>not <span class="_5 blank"> </span>proteins. <span class="_1 blank"> </span>Thus <span class="_1 blank"> </span>dialysis <span class="_1 blank"> </span>retains <span class="_5 blank"> </span>large <span class="_1 blank"> </span>pro-</div><div class="t m3 x16 h12 y2f ff6 fsd fc4 sc0 ls31 wsb">teins <span class="_5 blank"> </span>within <span class="_7 blank"> </span>the <span class="_7 blank"> </span>membranous <span class="_5 blank"> </span>bag <span class="_7 blank"> </span>or <span class="_7 blank"> </span>tube <span class="_5 blank"> </span>while <span class="_7 blank"> </span>allow-</div><div class="t m3 x16 h12 y30 ff6 fsd fc4 sc0 ls31 wsb">ing <span class="_8 blank"> </span>the <span class="_8 blank"> </span>concentration <span class="_8 blank"> </span>of <span class="_8 blank"> </span>other <span class="_8 blank"> </span>solutes <span class="_8 blank"> </span>in <span class="_8 blank"> </span>the <span class="_8 blank"> </span>protein</div><div class="t m3 x16 h12 y31 ff6 fsd fc4 sc0 ls31 wsb">preparation <span class="_1 blank"> </span>to <span class="_1 blank"> </span>change <span class="_5 blank"> </span>until <span class="_1 blank"> </span>they <span class="_5 blank"> </span>come <span class="_1 blank"> </span>into <span class="_1 blank"> </span>equilibrium</div><div class="t m3 x16 h12 y32 ff6 fsd fc4 sc0 ls31 wsb">with <span class="_1 blank"> </span>the solution <span class="_1 blank"> </span>outside <span class="_1 blank"> </span>the <span class="_1 blank"> </span>membrane. <span class="_1 blank"> </span>Dialysis might</div><div class="t m3 x16 h12 y33 ff6 fsd fc4 sc0 ls31 wsb">be <span class="_0 blank"></span>used, <span class="_0 blank"></span>for <span class="_3 blank"></span>example, to <span class="_3 blank"></span>remove ammonium <span class="_0 blank"></span>sulfate <span class="_3 blank"></span>from</div><div class="t m3 x16 h12 y34 ff6 fsd fc4 sc0 ls31 wsb">the <span class="_1 blank"> </span>protein <span class="_5 blank"> </span>preparation.</div><div class="t m3 x17 h12 y35 ff6 fsd fc4 sc0 ls31 wsb">The <span class="_7 blank"> </span>most <span class="_7 blank"> </span>powerful <span class="_7 blank"> </span>methods <span class="_7 blank"> </span>for <span class="_6 blank"> </span>fractionating <span class="_7 blank"> </span>pro-</div><div class="t m3 x16 h12 y36 ff6 fsd fc4 sc0 ls31 wsb">teins make use of <span class="ff9 ls35">column chromatography<span class="_3 blank"></span>,<span class="_a blank"> </span><span class="ff6 ls31">which</span></span></div><div class="t m3 x16 h12 y37 ff6 fsd fc4 sc0 ls31 wsb">takes <span class="_7 blank"> </span>advantage <span class="_7 blank"> </span>of <span class="_7 blank"> </span>differences <span class="_7 blank"> </span>in <span class="_7 blank"> </span>protein <span class="_7 blank"> </span>charge, <span class="_7 blank"> </span>size,</div><div class="t m3 x1e h16 y4c ffa fs12 fc4 sc0 ls36 ws24">3.3 <span class="ffb ls37 wsb">Wo<span class="_1 blank"> </span>r<span class="_1 blank"> </span>k<span class="_1 blank"> </span>i<span class="_1 blank"> </span>n<span class="_1 blank"> </span>g<span class="_1 blank"> </span> <span class="_5 blank"> </span>w<span class="_1 blank"> </span>i<span class="_1 blank"> </span>t<span class="_1 blank"> </span>h<span class="_1 blank"> </span> <span class="_5 blank"> </span>P<span class="_1 blank"> </span>r<span class="_1 blank"> </span>o<span class="_1 blank"> </span>t<span class="_1 blank"> </span>ei<span class="_1 blank"> </span>n<span class="_1 blank"> </span>s<span class="_b blank"> </span><span class="ff8 ls1 v0">89</span></span></div><div class="t m3 x1f h17 y4d ffc fse fc4 sc0 ls1">Primary</div><div class="t m3 x14 h17 y4e ffc fse fc4 sc0 ls1">structure</div><div class="t m3 x20 h17 y4d ffc fse fc4 sc0 ls1">Secondary</div><div class="t m3 x21 h17 y4e ffc fse fc4 sc0 ls1">structure</div><div class="t m3 x22 h17 y4d ffc fse fc4 sc0 ls1">Tertiary</div><div class="t m3 x23 h17 y4e ffc fse fc4 sc0 ls1">structure</div><div class="t m3 x1a h17 y4d ffc fse fc4 sc0 ls1">Quaternary</div><div class="t m3 x1b h17 y4e ffc fse fc4 sc0 ls1">structure</div><div class="t m3 x15 h18 y4f ffd fse fc4 sc0 ls1 wsb">Amino acid residues</div><div class="t m3 xa h18 y50 ffd fse fc4 sc0 ls1">Lys</div><div class="t m3 xa h18 y51 ffd fse fc4 sc0 ls1">Lys</div><div class="t m3 xa h18 y52 ffd fse fc4 sc0 ls1">Gly</div><div class="t m3 xa h18 y53 ffd fse fc4 sc0 ls1">Gly</div><div class="t m3 xa h18 y54 ffd fse fc4 sc0 ls1">Leu</div><div class="t m3 xa h18 y55 ffd fse fc4 sc0 ls1">Val</div><div class="t m3 xa h18 y56 ffd fse fc4 sc0 ls1">Ala</div><div class="t m3 xa h18 y57 ffd fse fc4 sc0 ls1">His</div><div class="t m3 x24 h18 y58 ffd fse fc4 sc0 ls1 wsb">Helix<span class="_c blank"> </span>Polypeptide chain<span class="_d blank"> </span>Assembled subunits</div><div class="t m5 x25 h19 y59 ffe fs13 fc4 sc0 ls1">!</div><div class="t m3 x15 h1a y5a ff8 fs12 fc5 sc0 ls36 wsb">FIGURE <span class="_5 blank"> </span>3\u201316<span class="_e blank"> </span><span class="fff fse fc4 ls38">Levels <span class="_1 blank"> </span>of <span class="_5 blank"> </span>structure <span class="_5 blank"> </span>in <span class="_5 blank"> </span>proteins. <span class="ff10 ls39">Th<span class="_1 blank"> </span>e<span class="_1 blank"> </span> <span class="_7 blank"> </span><span class="ff11 ls2a">primary <span class="_5 blank"> </span>structure</span></span></span></div><div class="t m3 x15 h1b y5b ff10 fse fc4 sc0 ls38 wsb">consists <span class="_0 blank"></span>of <span class="_0 blank"></span>a <span class="_3 blank"></span>sequence of <span class="_3 blank"></span>amino acids <span class="_0 blank"></span>linked <span class="_3 blank"></span>together by <span class="_3 blank"></span>peptide bonds</div><div class="t m3 x15 h1b y5c ff10 fse fc4 sc0 ls38 wsb">and <span class="_5 blank"> </span>includes <span class="_7 blank"> </span>any <span class="_7 blank"> </span>disulfide <span class="_5 blank"> </span>bonds. <span class="_5 blank"> </span>T<span class="_0 blank"></span>he <span class="_5 blank"> </span>resulting <span class="_7 blank"> </span>polypeptide <span class="_7 blank"> </span>can <span class="_7 blank"> </span>be</div><div class="t m3 x15 h1b y5d ff10 fse fc4 sc0 ls38 wsb">coiled <span class="_5 blank"> </span>into <span class="_1 blank"> </span>units <span class="_5 blank"> </span>of <span class="_5 blank"> </span><span class="ff11 ls2b">secondary <span class="_5 blank"> </span>structure,<span class="_f blank"> </span></span>such <span class="_1 blank"> </span>as <span class="_5 blank"> </span>an <span class="_5 blank"> </span><span class="ff12 ls2c">!</span><span class="ws25">helix<span class="ff11 ls2d">.</span></span><span class="ls39">Th<span class="_1 blank"> </span>e<span class="_1 blank"> </span> <span class="_5 blank"> </span>h<span class="_1 blank"> </span>e<span class="_1 blank"> </span>-</span></div><div class="t m3 x16 h1b y5a ff10 fse fc4 sc0 ls38 wsb">lix <span class="_1 blank"> </span>is <span class="_5 blank"> </span>a <span class="_1 blank"> </span>part <span class="_5 blank"> </span>of <span class="_1 blank"> </span>the <span class="_1 blank"> </span><span class="ff11 ls2a">ter<span class="_1 blank"> </span>tiary <span class="_5 blank"> </span>structure<span class="_10 blank"> </span></span>of <span class="_1 blank"> </span>the <span class="_5 blank"> </span>folded <span class="_1 blank"> </span>polypeptide, <span class="_5 blank"> </span>whic<span class="_0 blank"></span>h</div><div class="t m3 x16 h1b y5b ff10 fse fc4 sc0 ls38 wsb">is <span class="_1 blank"> </span>itself <span class="_5 blank"> </span>one <span class="_5 blank"> </span>of <span class="_1 blank"> </span>the <span class="_5 blank"> </span>subunits <span class="_1 blank"> </span>that <span class="_5 blank"> </span>make <span class="_1 blank"> </span>up <span class="_5 blank"> </span>the <span class="_5 blank"> </span><span class="ff11 ls2a">quaternary <span class="_5 blank"> </span>structure<span class="_10 blank"> </span></span><span class="ls3a">of</span></div><div class="t m3 x16 h1b y5c ff10 fse fc4 sc0 ls38 wsb">the <span class="_1 blank"> </span>multisubunit <span class="_1 blank"> </span>protein, <span class="_5 blank"> </span>in <span class="_1 blank"> </span>this <span class="_1 blank"> </span>case <span class="_5 blank"> </span>hemoglobin.</div><div class="t m3 x26 h1c y5e ff13 fse fc0 sc0 ls2e wsb">8885d_c03_089 12/23/03 11:06 AM Page 89 mac111 mac111:reb:</div></div><div class="c x3 y6 w2 h4"><div class="t m1 x27 hf y5f ff4 fs1 fc1 sc0 ls1 ws17">E<span class="fsb ls3b ws26">STRUTURA <span class="ls3c ws27">DA S<span class="_11 blank"> </span></span></span>P<span class="fsb ls1d ws19">ROTEÍNAS</span></div><div class="t m1 x14 h1d y60 ff4 fs14 fc0 sc0 ls1 wsb">Estrutura </div><div class="t m1 x14 h1e y61 ff4 fs14 fc0 sc0 ls1 ws28">Primária <span class="wsb v1">Estrutura </span></div><div class="t m1 x28 h1f y61 ff4 fs14 fc0 sc0 ls1 ws29">Secundária <span class="wsb v1">Estrutura </span></div><div class="t m1 x29 h1d y62 ff4 fs14 fc0 sc0 ls1 ws2a">T<span class="_3 blank"></span>erciária</div><div class="t m1 x2a h1d y60 ff4 fs14 fc0 sc0 ls1 wsb">Estrutura </div><div class="t m1 x2b h1d y61 ff4 fs14 fc0 sc0 ls1 ws2a">Quaternária</div><div class="t m1 x13 h10 y17 ff2 fsc fc3 sc0 ls1e ws1a">Newsholme <span class="ls1f wsb">E, <span class="ls20 ws1b">Leech </span><span class="ls21">A. <span class="ls22 ws1c">Functional <span class="ls23 ws1d">Biochemistry <span class="ls24 ws1e">in </span></span></span></span></span><span class="ws1f">Health <span class="ls25 ws20">and </span><span class="ws21">Disease<span class="ls26 wsb">. John </span></span><span class="ls27">Wiley <span class="ls28 wsb">& <span class="_0 blank"></span>Sons; 2011<span class="ls26">. </span></span></span></span></div></div><div class="c x3 yc w2 h4"><div class="t m1 x15 h20 y63 ff5 fsc fc7 sc0 ls1e ws2b">Nutrição <span class="ls2f wsb">no <span class="ls21 ws2c">Exercício </span><span class="ls25">e </span></span><span class="ws2d">Desp<span class="_0 blank"></span>orto <span class="ls21 wsb">Sergio Veloso, 2013 | <span class="ls1 ws2e">srsveloso@gmail.com</span></span></span></div><div class="t m1 x2c h9 y64 ff4 fs5 fc1 sc0 ls30">F<span class="fs6 ls3d ws2f">UNÇÕES <span class="ls3e ws30">DA S<span class="_12 blank"> </span></span></span><span class="ls0">P<span class="fs6 ls11 wsa">ROTEÍ<span class="_1 blank"> </span>NAS</span></span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf4" class="pf w0 h0" data-page-no="4"><div class="pc pc4 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg4.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">4</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x2d h1d y65 ff4 fs14 fc8 sc0 ls3f">P<span class="fsa ls42 ws31">ROTEÍ<span class="_0 blank"></span>NAS</span></div><div class="t m1 x2d h1d y66 ff4 fs14 fc9 sc0 ls1 ws2a">Estrutura</div><div class="t m1 x2e h1d y67 ff4 fs14 fc9 sc0 ls1 ws2a">Enzimas</div><div class="t m1 x2f h1d y68 ff4 fs14 fc9 sc0 ls1 ws2a">Hormonas</div><div class="t m1 x2c h1d y69 ff4 fs14 fc9 sc0 ls1 ws2a">Canais</div><div class="t m1 x30 h1d y6a ff4 fs14 fc9 sc0 ls1 ws2a">Receptores</div><div class="t m1 x31 h1d y6b ff4 fs14 fc9 sc0 ls1 ws2a">Anticorpos</div><div class="t m1 x32 h1d y6c ff4 fs14 fc9 sc0 ls1 wsb">Equilíbrio </div><div class="t m1 x21 h1d y6d ff4 fs14 fc9 sc0 ls43 ws32">Acido<span class="ls1 ws2a">-Base</span></div><div class="t m1 x33 h1d y6e ff4 fs14 fc9 sc0 ls1 ws2a">Equilíbrio</div><div class="t m1 x2d h1d y6f ff4 fs14 fc9 sc0 ls44 ws33">Hídrico</div><div class="t m1 x4 h1d y70 ff4 fs14 fc9 sc0 ls1 ws2a">T<span class="_3 blank"></span>ransporte</div></div><div class="c x3 yc w2 h4"><div class="t m1 x34 h21 y71 ff4 fs6 fc1 sc0 ls1 ws34">E<span class="fs8 ls45 ws35">NZIMAS</span></div></div><div class="c x35 y72 w4 h22"><div class="t m6 x36 h23 y73 ff14 fs15 fc4 sc0 ls46 ws36">50 / <span class="ff15 ls47 wsb">CHAPTER 7</span></div><div class="t m6 x37 h24 y74 ff16 fs16 fc0 sc0 ls1 wsb">Enzyme site<span class="_13 blank"> </span>Substrate</div><div class="t m6 x38 h24 y75 ff16 fs16 fc0 sc0 ls1">1</div><div class="t m6 x21 h24 y76 ff16 fs16 fc0 sc0 ls1">1</div><div class="t m6 x39 h24 y77 ff16 fs16 fc0 sc0 ls1">3</div><div class="t m6 x3a h24 y78 ff16 fs16 fc0 sc0 ls40">2<span class="ls1 v2">2</span></div><div class="t m6 x3b h24 y79 ff16 fs16 fc0 sc0 ls1">4</div><div class="t m6 x3c h24 y75 ff16 fs16 fc0 sc0 ls1">3</div><div class="t m6 x36 h25 y7a ff17 fs15 fca sc0 ls47 wsb">Figure 7\u20131.<span class="_14 blank"> </span><span class="ff15 fs17 fc4 ls48">Planar representation of the \u201cthree-</span></div><div class="t m6 x36 h25 y7b ff15 fs17 fc4 sc0 ls48 wsb">point attachment\u201d of a substrate to the active site of an</div><div class="t m6 x36 h25 y7c ff15 fs17 fc4 sc0 ls48 wsb">enzyme. Although atoms 1 and 4 are identical, once</div><div class="t m6 x36 h25 y7d ff15 fs17 fc4 sc0 ls48 wsb">atoms 2 and 3 are bound to their complementary sites</div><div class="t m6 x36 h25 y7e ff15 fs17 fc4 sc0 ls48 wsb">on the enzyme, only atom 1 can bind. Once bound to</div><div class="t m6 x36 h25 y7f ff15 fs17 fc4 sc0 ls48 wsb">an enzyme, apparently identical atoms thus may be dis-</div><div class="t m6 x36 h25 y80 ff15 fs17 fc4 sc0 ls48 wsb">tinguishable, permitting a stereospecific chemical</div><div class="t m6 x36 h25 y81 ff15 fs17 fc4 sc0 ls48">change.</div><div class="t m6 x14 h26 y82 ff18 fs15 fca sc0 ls46">2.</div><div class="t m7 x3d h27 y82 ff18 fs15 fc4 sc0 ls47 ws37">Transferases <span class="ff19 wsb">catalyze <span class="_9 blank"> </span>transfer <span class="_f blank"> </span>of <span class="_9 blank"> </span>groups <span class="_f blank"> </span>such <span class="_9 blank"> </span>as</span></div><div class="t m7 x3d h27 y83 ff19 fs15 fc4 sc0 ls47 wsb">methyl <span class="_5 blank"> </span>or <span class="_5 blank"> </span>glycosyl <span class="_7 blank"> </span>groups <span class="_5 blank"> </span>from <span class="_5 blank"> </span>a <span class="_7 blank"> </span>donor <span class="_5 blank"> </span>molecule</div><div class="t m7 x3d h27 y84 ff19 fs15 fc4 sc0 ls47 wsb">to an acceptor molecule.</div><div class="t m6 x14 h26 y85 ff18 fs15 fca sc0 ls46">3.</div><div class="t m7 x3d h27 y85 ff18 fs15 fc4 sc0 ls47 ws38">Hydrolases <span class="ff19 wsb">catalyze <span class="_e blank"> </span>the <span class="_15 blank"> </span>hydrolytic <span class="_e blank"> </span>cleavage <span class="_15 blank"> </span>of</span></div><div class="t m7 x3d h28 y86 ff19 fs15 fc4 sc0 ls1 ws39">C<span class="ff1a ls41">\u23af</span><span class="ls47 wsb">C, <span class="_8 blank"> </span>C<span class="ff1a ls41">\u23af</span>O, <span class="_10 blank"> </span>C</span><span class="ff1a ws3a">\u23af</span><span class="ls47 wsb">N, <span class="_8 blank"> </span>P<span class="ff1a ls41">\u23af</span>O, <span class="_8 blank"> </span>and <span class="_8 blank"> </span>certain <span class="_10 blank"> </span>other</span></div><div class="t m7 x3d h27 y87 ff19 fs15 fc4 sc0 ls47 wsb">bonds, including acid anhydride bonds.</div><div class="t m6 x14 h26 y88 ff18 fs15 fca sc0 ls46">4.</div><div class="t m7 x3d h28 y88 ff18 fs15 fc4 sc0 ls47 ws3b">Lyases <span class="ff19 wsb">catalyze cleavage of <span class="_0 blank"></span>C<span class="ff1a ls41">\u23af</span>C, C<span class="ff1a ls41">\u23af</span>O, C<span class="ff1a ls1 ws3a">\u23af<span class="ff19">N,</span></span></span></div><div class="t m7 x3d h27 y89 ff19 fs15 fc4 sc0 ls47 wsb">and <span class="_f blank"> </span>other <span class="_9 blank"> </span>bonds <span class="_f blank"> </span>by <span class="_9 blank"> </span>elimination, <span class="_f blank"> </span>leaving <span class="_9 blank"> </span>double</div><div class="t m7 x3d h27 y8a ff19 fs15 fc4 sc0 ls47 wsb">bonds, and also add groups to double bonds.</div><div class="t m6 x14 h26 y8b ff18 fs15 fca sc0 ls46">5.</div><div class="t m7 x3d h27 y8b ff18 fs15 fc4 sc0 ls47 ws3c">Isomerases <span class="ff19 wsb">catalyze <span class="_16 blank"> </span>geometric <span class="_16 blank"> </span>or <span class="_16 blank"> </span>structural</span></div><div class="t m7 x3d h27 y8c ff19 fs15 fc4 sc0 ls47 wsb">changes within a single molecule.</div><div class="t m6 x14 h26 y8d ff18 fs15 fca sc0 ls46">6.</div><div class="t m7 x3d h27 y8d ff18 fs15 fc4 sc0 ls47 ws3d">Ligases <span class="ff19 wsb">catalyze the <span class="_1 blank"> </span>joining together <span class="_1 blank"> </span>of two mole-</span></div><div class="t m7 x3d h27 y8e ff19 fs15 fc4 sc0 ls47 wsb">cules, coupled <span class="_0 blank"></span>to <span class="_0 blank"></span>the hydrolysis <span class="_0 blank"></span>of <span class="_0 blank"></span>a <span class="_0 blank"></span>pyrophospho-</div><div class="t m7 x3d h27 y8f ff19 fs15 fc4 sc0 ls47 wsb">ryl <span class="_7 blank"> </span>group <span class="_7 blank"> </span>in <span class="_7 blank"> </span>ATP <span class="_7 blank"> </span>or <span class="_7 blank"> </span>a <span class="_7 blank"> </span>similar <span class="_7 blank"> </span>nucleoside <span class="_7 blank"> </span>triphos-</div><div class="t m7 x3d h27 y90 ff19 fs15 fc4 sc0 ls47">phate.</div><div class="t m7 x3e h27 y91 ff19 fs15 fc4 sc0 ls47 wsb">Despite <span class="_17 blank"> </span>the <span class="_17 blank"> </span>many <span class="_17 blank"> </span>advantages <span class="_17 blank"> </span>of <span class="_17 blank"> </span>the <span class="_17 blank"> </span>IUB <span class="_17 blank"> </span>system,</div><div class="t m7 x36 h27 y92 ff19 fs15 fc4 sc0 ls47 wsb">texts <span class="_6 blank"> </span>tend <span class="_8 blank"> </span>to <span class="_6 blank"> </span>refer <span class="_8 blank"> </span>to <span class="_6 blank"> </span>most <span class="_6 blank"> </span>enzymes <span class="_8 blank"> </span>by <span class="_6 blank"> </span>their <span class="_8 blank"> </span>older <span class="_6 blank"> </span>and</div><div class="t m7 x36 h27 y93 ff19 fs15 fc4 sc0 ls47 wsb">shorter, albeit sometimes ambiguous names.</div><div class="t m6 x36 h29 y94 ff1b fs18 fca sc0 ls49 wsb">PROSTHETIC GROUPS, COFACTORS, </div><div class="t m6 x36 h29 y95 ff1b fs18 fca sc0 ls4a wsb">& COENZYMES PLAY IMPORTANT </div><div class="t m6 x36 h29 y96 ff1b fs18 fca sc0 ls4a wsb">ROLES IN CATALYSIS</div><div class="t m7 x36 h27 y97 ff19 fs15 fc4 sc0 ls47 wsb">Many enzymes contain small nonprotein molecules and</div><div class="t m7 x36 h27 y98 ff19 fs15 fc4 sc0 ls47 wsb">metal <span class="_5 blank"> </span>ions <span class="_5 blank"> </span>that <span class="_5 blank"> </span>participate <span class="_5 blank"> </span>directly <span class="_5 blank"> </span>in <span class="_7 blank"> </span>substrate <span class="_5 blank"> </span>binding</div><div class="t m7 x36 h27 y99 ff19 fs15 fc4 sc0 ls47 wsb">or <span class="_1 blank"> </span>catalysis. <span class="_5 blank"> </span>Termed <span class="_1 blank"> </span><span class="ff18">prosthetic <span class="_5 blank"> </span>groups, <span class="_1 blank"> </span>cofactors,<span class="_e blank"> </span></span><span class="ls4b">and</span></div><div class="t m7 x36 h27 y9a ff18 fs15 fc4 sc0 ls47 ws3e">coenzymes, <span class="ff19 wsb">these <span class="_6 blank"> </span>extend <span class="_6 blank"> </span>the <span class="_8 blank"> </span>repertoire <span class="_6 blank"> </span>of <span class="_8 blank"> </span>catalytic <span class="_6 blank"> </span>ca-</span></div><div class="t m7 x36 h27 y9b ff19 fs15 fc4 sc0 ls47 wsb">pabilities <span class="_1 blank"> </span>beyond <span class="_5 blank"> </span>those <span class="_5 blank"> </span>afforded <span class="_1 blank"> </span>by <span class="_5 blank"> </span>the <span class="_1 blank"> </span>limited <span class="_5 blank"> </span>number</div><div class="t m7 x36 h27 y9c ff19 fs15 fc4 sc0 ls47 wsb">of <span class="_e blank"> </span>functional <span class="_18 blank"> </span>groups <span class="_18 blank"> </span>present <span class="_e blank"> </span>on <span class="_18 blank"> </span>the <span class="_e blank"> </span>aminoacyl <span class="_18 blank"> </span>side</div><div class="t m7 x36 h27 y9d ff19 fs15 fc4 sc0 ls47 wsb">chains of peptides.</div><div class="t m8 x3f h2a y9e ff1b fs19 fca sc0 ls4c wsb">Prosthetic Groups Are Tightly Integrated</div><div class="t m8 x3f h2a y9f ff1b fs19 fca sc0 ls4c wsb">Into an Enzyme\u2019s Structure</div><div class="t m7 x3f h27 ya0 ff19 fs15 fc4 sc0 ls1 wsb">Prosthetic groups are distinguished by their tight, stable</div><div class="t m7 x3f h27 ya1 ff19 fs15 fc4 sc0 ls47 wsb">incorporation <span class="_8 blank"> </span>into <span class="_8 blank"> </span>a <span class="_8 blank"> </span>protein\u2019s <span class="_8 blank"> </span>structure <span class="_10 blank"> </span>by <span class="_6 blank"> </span>covalent <span class="_10 blank"> </span>or</div><div class="t m7 x3f h27 ya2 ff19 fs15 fc4 sc0 ls47 wsb">noncovalent <span class="_f blank"> </span>forces. <span class="_10 blank"> </span>Examples <span class="_f blank"> </span>include <span class="_f blank"> </span>pyridoxal <span class="_f blank"> </span>phos-</div><div class="t m7 x3f h27 ya3 ff19 fs15 fc4 sc0 ls47 wsb">phate, <span class="_19 blank"> </span>flavin <span class="_19 blank"> </span>mononucleotide <span class="_19 blank"> </span>(FMN), <span class="_19 blank"> </span>flavin <span class="_19 blank"> </span>dinu-</div><div class="t m7 x3f h27 ya4 ff19 fs15 fc4 sc0 ls47 wsb">cleotide <span class="_18 blank"> </span>(FAD), <span class="_18 blank"> </span>thiamin <span class="_18 blank"> </span>pyrophosphate, <span class="_e blank"> </span>biotin, <span class="_18 blank"> </span>and</div><div class="t m7 x3f h27 ya5 ff19 fs15 fc4 sc0 ls47 wsb">the <span class="_1 blank"> </span>metal <span class="_1 blank"> </span>ions <span class="_1 blank"> </span>of <span class="_5 blank"> </span>Co, <span class="_1 blank"> </span>Cu, <span class="_1 blank"> </span>Mg, <span class="_1 blank"> </span>Mn, <span class="_1 blank"> </span>Se, <span class="_5 blank"> </span>and <span class="_1 blank"> </span>Zn. <span class="_1 blank"> </span>Metals</div><div class="t m7 x3f h27 ya6 ff19 fs15 fc4 sc0 ls47 wsb">are <span class="_8 blank"> </span>the <span class="_10 blank"> </span>most <span class="_8 blank"> </span>common <span class="_10 blank"> </span>prosthetic <span class="_8 blank"> </span>groups. <span class="_8 blank"> </span>The <span class="_10 blank"> </span>roughly</div><div class="t m7 x3f h27 ya7 ff19 fs15 fc4 sc0 ls47 wsb">one-third of all <span class="_17 blank"> </span>enzymes that contain tightly bound</div><div class="t m7 x3f h27 ya8 ff19 fs15 fc4 sc0 ls47 wsb">metal ions are termed <span class="ff18 ws3f">metalloenzymes. </span>Metal ions that</div><div class="t m7 x3f h27 ya9 ff19 fs15 fc4 sc0 ls47 wsb">participate <span class="_10 blank"> </span>in <span class="_10 blank"> </span>redox <span class="_f blank"> </span>reactions <span class="_10 blank"> </span>generally <span class="_10 blank"> </span>are <span class="_f blank"> </span>complexed</div><div class="t m7 x3f h27 yaa ff19 fs15 fc4 sc0 ls47 wsb">to <span class="_5 blank"> </span>prosthetic <span class="_5 blank"> </span>groups <span class="_5 blank"> </span>such <span class="_7 blank"> </span>as <span class="_5 blank"> </span>heme <span class="_5 blank"> </span>(Chapter <span class="_5 blank"> </span>6) <span class="_5 blank"> </span>or <span class="_7 blank"> </span>iron-</div><div class="t m7 x3f h27 yab ff19 fs15 fc4 sc0 ls47 wsb">sulfur <span class="_8 blank"> </span>clusters <span class="_8 blank"> </span>(Chapter <span class="_8 blank"> </span>12). <span class="_8 blank"> </span>Metals <span class="_8 blank"> </span>also <span class="_8 blank"> </span>may <span class="_8 blank"> </span>facilitate</div><div class="t m7 x3f h27 yac ff19 fs15 fc4 sc0 ls47 wsb">the binding and <span class="_0 blank"></span>orientation of <span class="_0 blank"></span>substrates, the <span class="_0 blank"></span>formation</div><div class="t m7 x3f h27 yad ff19 fs15 fc4 sc0 ls47 wsb">of <span class="_5 blank"> </span>covalent <span class="_7 blank"> </span>bonds <span class="_7 blank"> </span>with <span class="_7 blank"> </span>reaction <span class="_5 blank"> </span>intermediates <span class="_7 blank"> </span>(Co</div><div class="t m9 x40 h2b yae ff19 fs1a fc4 sc0 ls1">2</div><div class="t ma x41 h2c yaf ff19 fs1b fc4 sc0 ls1">+</div><div class="t m7 x42 h27 yad ff19 fs15 fc4 sc0 ls4d">in</div><div class="t m7 x3f h27 yb0 ff19 fs15 fc4 sc0 ls47 wsb">coenzyme <span class="_5 blank"> </span>B</div><div class="t m9 x43 h2b yb1 ff19 fs1a fc4 sc0 ls4e">12</div><div class="t m7 x44 h27 yb0 ff19 fs15 fc4 sc0 ls47 wsb">), <span class="_5 blank"> </span>or <span class="_5 blank"> </span>interaction <span class="_1 blank"> </span>with <span class="_5 blank"> </span>substrates <span class="_5 blank"> </span>to <span class="_5 blank"> </span>render</div><div class="t m7 x3f h27 yb2 ff19 fs15 fc4 sc0 ls47 wsb">them <span class="_18 blank"> </span>more <span class="_e blank"> </span><span class="ff18 ws40">electrophilic </span>(electron-poor) <span class="_e blank"> </span>or <span class="_18 blank"> </span><span class="ff18 ls4b">nucleo-</span></div><div class="t m7 x3f h27 yb3 ff18 fs15 fc4 sc0 ls4b ws41">philic <span class="ff19 ls47">(electron-rich).</span></div><div class="t m8 x3f h2a yb4 ff1b fs19 fca sc0 ls4c wsb">Cofactors Associate Reversibly With</div><div class="t m8 x3f h2a yb5 ff1b fs19 fca sc0 ls4c wsb">Enzymes or Substrates</div><div class="t m7 x3f h27 yb6 ff18 fs15 fc4 sc0 ls47 ws42">Cofactors <span class="ff19 wsb">serve <span class="_5 blank"> </span>functions <span class="_5 blank"> </span>similar <span class="_1 blank"> </span>to <span class="_5 blank"> </span>those <span class="_5 blank"> </span>of <span class="_5 blank"> </span>prosthetic</span></div><div class="t m7 x3f h27 yb7 ff19 fs15 fc4 sc0 ls47 wsb">groups <span class="_8 blank"> </span>but <span class="_10 blank"> </span>bind <span class="_8 blank"> </span>in <span class="_10 blank"> </span>a <span class="_10 blank"> </span>transient, <span class="_8 blank"> </span>dissociable <span class="_10 blank"> </span>manner <span class="_8 blank"> </span>ei-</div><div class="t m7 x3f h27 yb8 ff19 fs15 fc4 sc0 ls47 wsb">ther <span class="_7 blank"> </span>to <span class="_7 blank"> </span>the <span class="_7 blank"> </span>enzyme <span class="_7 blank"> </span>or <span class="_6 blank"> </span>to <span class="_7 blank"> </span>a <span class="_7 blank"> </span>substrate <span class="_7 blank"> </span>such <span class="_6 blank"> </span>as <span class="_7 blank"> </span>ATP. <span class="_7 blank"> </span>Un-</div><div class="t m7 x3f h27 yb9 ff19 fs15 fc4 sc0 ls47 wsb">like <span class="_17 blank"> </span>the <span class="_17 blank"> </span>stably <span class="_9 blank"> </span>associated <span class="_17 blank"> </span>prosthetic <span class="_17 blank"> </span>groups, <span class="_17 blank"> </span>cofactors</div><div class="t m7 x3f h27 yba ff19 fs15 fc4 sc0 ls47 wsb">therefore <span class="_8 blank"> </span>must <span class="_8 blank"> </span>be <span class="_6 blank"> </span>present <span class="_8 blank"> </span>in <span class="_8 blank"> </span>the <span class="_8 blank"> </span>medium <span class="_8 blank"> </span>surrounding</div><div class="t m7 x3f h27 ybb ff19 fs15 fc4 sc0 ls47 wsb">the <span class="_10 blank"> </span>enzyme <span class="_10 blank"> </span>for <span class="_10 blank"> </span>catalysis <span class="_10 blank"> </span>to <span class="_10 blank"> </span>occur. <span class="_10 blank"> </span>The <span class="_8 blank"> </span>most <span class="_10 blank"> </span>common</div><div class="t m7 x3f h27 ybc ff19 fs15 fc4 sc0 ls47 wsb">cofactors <span class="_9 blank"> </span>also <span class="_f blank"> </span>are <span class="_9 blank"> </span>metal <span class="_9 blank"> </span>ions. <span class="_f blank"> </span>Enzymes <span class="_9 blank"> </span>that <span class="_9 blank"> </span>require <span class="_f blank"> </span>a</div><div class="t m7 x3f h27 ybd ff19 fs15 fc4 sc0 ls47 wsb">metal ion <span class="_0 blank"></span>cofactor <span class="_0 blank"></span>are termed <span class="_0 blank"></span><span class="ff18">metal-activated <span class="_0 blank"></span>enzymes</span></div><div class="t m7 x3f h27 ybe ff19 fs15 fc4 sc0 ls47 wsb">to <span class="_1a blank"> </span>distinguish <span class="_1a blank"> </span>them <span class="_1a blank"> </span>from <span class="_1a blank"> </span>the <span class="_1a blank"> </span><span class="ff18 ws43">metalloenzymes </span><span class="ls4d">for</span></div><div class="t m7 x3f h27 ybf ff19 fs15 fc4 sc0 ls47 wsb">which metal ions serve as prosthetic groups.</div><div class="t m8 x3f h2a yc0 ff1b fs19 fca sc0 ls4c wsb">Coenzymes Serve as Substrate Shuttles</div><div class="t m7 x3f h27 yc1 ff18 fs15 fc4 sc0 ls47 ws44">Coenzymes <span class="ff19 wsb">serve <span class="_1b blank"> </span>as <span class="_1b blank"> </span>recyclable <span class="_1b blank"> </span>shuttles\u2014or <span class="_1b blank"> </span>group</span></div><div class="t m7 x3f h27 yc2 ff19 fs15 fc4 sc0 ls47 wsb">transfer <span class="_6 blank"> </span>reagents\u2014that <span class="_7 blank"> </span>transport <span class="_6 blank"> </span>many <span class="_6 blank"> </span>substrates <span class="_6 blank"> </span>from</div><div class="t m7 x3f h27 yc3 ff19 fs15 fc4 sc0 ls47 wsb">their <span class="_10 blank"> </span>point <span class="_f blank"> </span>of <span class="_10 blank"> </span>generation <span class="_10 blank"> </span>to <span class="_f blank"> </span>their <span class="_10 blank"> </span>point <span class="_10 blank"> </span>of <span class="_f blank"> </span>utilization.</div><div class="t m7 x3f h27 yc4 ff19 fs15 fc4 sc0 ls47 wsb">Association <span class="_5 blank"> </span>with <span class="_5 blank"> </span>the <span class="_5 blank"> </span>coenzyme <span class="_5 blank"> </span>also <span class="_5 blank"> </span>stabilizes <span class="_7 blank"> </span>substrates</div><div class="t m7 x3f h27 yc5 ff19 fs15 fc4 sc0 ls47 wsb">such <span class="_5 blank"> </span>as <span class="_5 blank"> </span>hydrogen <span class="_5 blank"> </span>atoms <span class="_5 blank"> </span>or <span class="_5 blank"> </span>hydride <span class="_5 blank"> </span>ions <span class="_5 blank"> </span>that <span class="_7 blank"> </span>are <span class="_5 blank"> </span>unsta-</div><div class="t m7 x3f h27 yc6 ff19 fs15 fc4 sc0 ls47 wsb">ble <span class="_e blank"> </span>in <span class="_e blank"> </span>the <span class="_15 blank"> </span>aqueous <span class="_e blank"> </span>environment <span class="_e blank"> </span>of <span class="_e blank"> </span>the <span class="_15 blank"> </span>cell. <span class="_e blank"> </span>Other</div><div class="t m7 x3f h27 yc7 ff19 fs15 fc4 sc0 ls47 wsb">chemical moieties <span class="_18 blank"> </span>transported by coenzymes <span class="_18 blank"> </span>include</div><div class="t m7 x3f h27 yc8 ff19 fs15 fc4 sc0 ls47 wsb">methyl <span class="_5 blank"> </span>groups <span class="_1 blank"> </span>(folates), <span class="_5 blank"> </span>acyl <span class="_5 blank"> </span>groups <span class="_5 blank"> </span>(coenzyme <span class="_1 blank"> </span>A), <span class="_5 blank"> </span>and</div><div class="t m7 x3f h27 yc9 ff19 fs15 fc4 sc0 ls47 wsb">oligosaccharides (dolichol).</div><div class="t m8 x3f h2a yca ff1b fs19 fca sc0 ls4c wsb">Many Coenzymes, Cofactors, & Prosthetic</div><div class="t m8 x3f h2a ycb ff1b fs19 fca sc0 ls4c wsb">Groups Are Derivatives of B Vitamins</div><div class="t m7 x3f h27 ycc ff19 fs15 fc4 sc0 ls47 wsb">The water-soluble B vitamins <span class="_0 blank"></span>supply important compo-</div><div class="t m7 x3f h27 ycd ff19 fs15 fc4 sc0 ls47 wsb">nents <span class="_10 blank"> </span>of <span class="_10 blank"> </span>numerous <span class="_8 blank"> </span>coenzymes. <span class="_10 blank"> </span>Many <span class="_10 blank"> </span>coenzymes <span class="_10 blank"> </span>con-</div><div class="t m7 x3f h27 yce ff19 fs15 fc4 sc0 ls47 wsb">tain, <span class="_10 blank"> </span>in <span class="_10 blank"> </span>addition, <span class="_10 blank"> </span>the <span class="_10 blank"> </span>adenine, <span class="_10 blank"> </span>ribose, <span class="_10 blank"> </span>and <span class="_8 blank"> </span>phosphoryl</div><div class="t m7 x3f h27 ycf ff19 fs15 fc4 sc0 ls47 wsb">moieties <span class="_7 blank"> </span>of <span class="_7 blank"> </span>AMP <span class="_7 blank"> </span>or <span class="_7 blank"> </span>ADP <span class="_7 blank"> </span>(Figure <span class="_7 blank"> </span>7\u20132). <span class="_7 blank"> </span><span class="ff18">Nicotinamide</span></div><div class="t m7 x3f h27 yd0 ff19 fs15 fc4 sc0 ls4b wsb">and <span class="_1 blank"> </span><span class="ff18 ws45">riboflavin </span><span class="ls47">are <span class="_1 blank"> </span>components <span class="_1 blank"> </span>of <span class="_1 blank"> </span>the <span class="_1 blank"> </span>redox <span class="_1 blank"> </span>coenzymes</span></div><div class="t m8 x45 h2d yd1 ff1c fs1c fc0 sc0 ls4f wsb">ch07.qxd <span class="_1c blank"></span> <span class="_1c blank"></span>2/13/2003 <span class="_1c blank"></span> <span class="_1c blank"></span>2:14 <span class="_1c blank"></span>PM <span class="_1c blank"></span> <span class="_1c blank"></span>Page <span class="_1c blank"></span>50</div></div><div class="c x3 yc w2 h4"><div class="t m1 x46 h10 yd2 ff2 fsc fc3 sc0 ls50 wsb">Murray <span class="ls23">R, Bender D, Botham <span class="ls51">KM, Kennelly PJ, </span><span class="ws46">Rodwell </span><span class="ls2f">V, Weil P<span class="_0 blank"></span>A. Harpers Il<span class="_0 blank"></span>lustrated Bioche<span class="_0 blank"></span>mistry 29th Edition. <span class="_0 blank"></span>McGraw<span class="ls1 ws2e">-</span><span class="ls1e">Hill Me<span class="_0 blank"></span>dical; 2<span class="_0 blank"></span>012.</span></span></span></div><div class="t m1 x47 h2e yd3 ff2 fs3 fc0 sc0 ls52 ws47">Substrato<span class="_1d blank"></span><span class="ls1 ws48">Enzima</span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf5" class="pf w0 h0" data-page-no="5"><div class="pc pc5 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg5.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">5</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x48 h21 yd4 ff4 fs6 fc1 sc0 ls1 ws34">E<span class="fs8 ls45 ws35">NZIMAS</span></div><div class="t m1 x13 h10 y17 ff2 fsc fc3 sc0 ls1e ws1a">Newsholme <span class="ls1f wsb">E, <span class="ls20 ws1b">Leech </span><span class="ls21">A. <span class="ls22 ws1c">Functional <span class="ls23 ws1d">Biochemistry <span class="ls24 ws1e">in </span></span></span></span></span><span class="ws1f">Health <span class="ls25 ws20">and </span><span class="ws21">Disease<span class="ls26 wsb">. John </span></span><span class="ls27">Wiley <span class="ls28 wsb">& <span class="_0 blank"></span>Sons; 2011<span class="ls26">. </span></span></span></span></div></div><div class="c x3 yc w2 h4"><div class="t m1 x39 h2f yd5 ff4 fs4 fc1 sc0 ls1 ws49">I<span class="fs2 ls54 ws4a">NIBIÇÃO <span class="ls55 ws4b">POR <span class="ls1 ws4c">COMPETIÇÃ<span class="_0 blank"></span>O</span></span></span></div><div class="t m1 x49 h2f yd6 ff4 fs4 fc2 sc0 ls53">R<span class="fs2 ls1 ws4d">EAÇÃO </span><span class="ls56 ws4e">\u201cN</span><span class="fs2 ls57 ws4f">ORMAL<span class="_1e blank"></span><span class="fs4 ls1">\u201d</span></span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf6" class="pf w0 h0" data-page-no="6"><div class="pc pc6 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg6.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">6</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c xb yd7 w5 h30"><div class="t mb x4a h31 yd8 ff1d fs1d fcb sc0 ls66 ws50">70 <span class="fs1e ls58 ws51">PART TWO<span class="_1f blank"> </span>FUNDAMENTALS OF SPORT AND EXERCISE BIOCHEMISTRY</span></div><div class="t mc x4b h32 yd9 ff1e fs1f fcc sc0 ls1">n</div><div class="t md x16 h33 yda ff1e fs20 fcc sc0 ls1">o</div><div class="t me x4c h34 ydb ff1e fs21 fcc sc0 ls1">i</div><div class="t mf x4d h35 ydc ff1e fs22 fcc sc0 ls1">t</div><div class="t m10 x4e h36 ydd ff1e fs23 fcc sc0 ls1">a</div><div class="t m11 x4f h37 yde ff1e fs24 fcc sc0 ls1">r</div><div class="t m12 x38 h38 ydf ff1e fs25 fcc sc0 ls1">t</div><div class="t m13 x22 h39 ye0 ff1e fs26 fcc sc0 ls1">n</div><div class="t m14 x50 h3a ye1 ff1e fs27 fcc sc0 ls1">e</div><div class="t m15 x51 h3b ye2 ff1e fs28 fcc sc0 ls1">c</div><div class="t m16 xb h3c ye3 ff1e fs29 fcc sc0 ls1">n</div><div class="t m17 x52 h3d ye4 ff1e fs2a fcc sc0 ls1">o</div><div class="t m18 x11 h3e ye5 ff1e fs2b fcc sc0 ls1">c</div><div class="t m19 x6 h3f ye6 ff1e fs2c fcc sc0 ls1">e</div><div class="t m1a x33 h40 ye7 ff1e fs2d fcc sc0 ls1">m</div><div class="t m1b x53 h41 ye8 ff1e fs2e fcc sc0 ls1">y</div><div class="t m1c x48 h42 ye9 ff1e fs2f fcc sc0 ls1">z</div><div class="t m1d x54 h43 yea ff1e fs30 fcc sc0 ls1">n</div><div class="t m1e x55 h44 yeb ff1e fs31 fcc sc0 ls1">e</div><div class="t m1f x35 h45 yec ff1e fs32 fcc sc0 ls1">d</div><div class="t m20 x8 h46 yed ff1e fs33 fcc sc0 ls1">e</div><div class="t m21 x56 h47 yee ff1e fs34 fcc sc0 ls1">s</div><div class="t m22 x7 h48 yef ff1e fs35 fcc sc0 ls1">a</div><div class="t m23 x57 h49 yf0 ff1e fs36 fcc sc0 ls1">e</div><div class="t m24 x49 h4a yf1 ff1e fs37 fcc sc0 ls1">r</div><div class="t m25 x58 h4b yf2 ff1e fs38 fcc sc0 ls1">c</div><div class="t m26 x59 h4c yf3 ff1e fs39 fcc sc0 ls1">n</div><div class="t m27 x5a h4d yf4 ff1e fs3a fcc sc0 ls1">I</div><div class="t m28 x5b h4e yf5 ff1e fs3b fcc sc0 ls1">n</div><div class="t m29 x5c h4f yf6 ff1e fs3c fcc sc0 ls1">o</div><div class="t m2a x4b h50 yf7 ff1e fs3d fcc sc0 ls1">i</div><div class="t m2b x5d h51 yf8 ff1e fs3e fcc sc0 ls1">t</div><div class="t m2c x4c h52 yf9 ff1e fs3f fcc sc0 ls1">a</div><div class="t m2d x5e h53 yfa ff1e fs40 fcc sc0 ls1">r</div><div class="t m2e x5f h54 yfb ff1e fs41 fcc sc0 ls1">t</div><div class="t m2f x4f h55 yfc ff1e fs42 fcc sc0 ls1">n</div><div class="t m30 x60 h56 yfd ff1e fs43 fcc sc0 ls1">e</div><div class="t m31 x23 h57 yfe ff1e fs44 fcc sc0 ls1">c</div><div class="t m32 x61 h58 yff ff1e fs45 fcc sc0 ls1">n</div><div class="t m33 x62 h59 y100 ff1e fs46 fcc sc0 ls1">o</div><div class="t m34 x63 h5a y101 ff1e fs47 fcc sc0 ls1">c</div><div class="t m35 x11 h5b y102 ff1e fs48 fcc sc0 ls1">e</div><div class="t m36 x64 h5c y103 ff1e fs49 fcc sc0 ls1">m</div><div class="t m37 x65 h5d y104 ff1e fs4a fcc sc0 ls1">y</div><div class="t m38 x66 h5e y105 ff1e fs4b fcc sc0 ls1">z</div><div class="t m39 x34 h5f y106 ff1e fs4c fcc sc0 ls1">n</div><div class="t m3a x9 h60 y107 ff1e fs4d fcc sc0 ls1">e</div><div class="t m3b x67 h42 y108 ff1e fs4e fcc sc0 ls1">l</div><div class="t m3c x68 h61 y109 ff1e fs4f fcc sc0 ls1">a</div><div class="t m3d x8 h62 y10a ff1e fs50 fcc sc0 ls1">m</div><div class="t m3e x69 h63 y10b ff1e fs51 fcc sc0 ls1">r</div><div class="t m3f x6a h64 y10c ff1e fs52 fcc sc0 ls1">o</div><div class="t m40 x57 h65 y10d ff1e fs53 fcc sc0 ls1">N</div><div class="t mb x59 h66 y10e ff1e fs54 fcc sc0 ls59">K<span class="fs55 ls1 v3">M</span></div><div class="t mb x6b h66 y10f ff1e fs54 fcc sc0 ls59">V<span class="fs55 ls67 v3">ma</span></div></div><div class="c x61 y110 w6 h67"><div class="t mb x6c h68 y111 ff1e fs55 fcc sc0 ls1">x</div></div><div class="c xb yd7 w5 h30"><div class="t mb x13 h66 y112 ff1e fs54 fcc sc0 ls1 wsb">Substrate Concentration</div><div class="t m41 x1f h69 y113 ff1e fs56 fcc sc0 ls1 wsb">Reaction Rate</div><div class="t mb x6b h66 y114 ff1e fs54 fcc sc0 ls59">V<span class="fs55 ls67 v3">ma</span></div></div><div class="c x61 y110 w6 h67"><div class="t mb x6c h68 y115 ff1e fs55 fcc sc0 ls1">x</div></div><div class="c xb yd7 w5 h30"><div class="t mb x4a h31 y116 ff1d fs1d fcb sc0 ls1 ws52">Figure 4.12<span class="_20 blank"> </span><span class="ff1f fcc ls5a ws53">Ef<span class="_0 blank"></span>fect of enzyme concentration<span class="_a blank"> </span>on reac-</span></div><div class="t mb x4a h6a y117 ff1f fs1d fcc sc0 ls5b ws54">tion rate</div><div class="t mb x0 h6b y118 ff20 fs57 fcc sc0 ls1 ws55">The ability of cells to adjust enzyme con-</div><div class="t mb x4a h6b y119 ff20 fs57 fcc sc0 ls5c ws56">centration in order to increase reaction rate<span class="_12 blank"> </span>is</div><div class="t mb x4a h6b y11a ff20 fs57 fcc sc0 ls1 ws57">one of the underpinning mechanisms by which</div><div class="t mb x4a h6b y11b ff20 fs57 fcc sc0 ls1 ws58">skeletal muscle adapts to endurance training.<span class="_a blank"> </span>W<span class="_0 blank"></span>ith</div><div class="t mb x4a h6b y11c ff20 fs57 fcc sc0 ls1 ws59">repeated bouts of endurance training, our muscle</div><div class="t mb x4a h6b y11d ff20 fs57 fcc sc0 ls1 ws5a">cells respond by making new proteins through the</div><div class="t mb x4a h6b y11e ff20 fs57 fcc sc0 ls5d ws5b">process of protein synthesis (see later sections),</div><div class="t mb x4a h6b y11f ff20 fs57 fcc sc0 ls5e ws5c">thus increasing enzyme concentration so that</div><div class="t mb x4a h6b y120 ff20 fs57 fcc sc0 ls1 ws5d">metabolic reactions operate at a greater rate. As</div><div class="t mb x4a h6b y121 ff20 fs57 fcc sc0 ls5f ws5e">such, the stress of exercise is reduced for a given</div><div class="t mb x4a h6b y122 ff20 fs57 fcc sc0 ls1 ws5f">absolute intensity (Holloszy & Coyle, 1984).</div><div class="t mb x4a h6c y123 ff1d fs57 fcb sc0 ls68 ws60">4.4.3<span class="_21 blank"> </span>Coenzymes and cofactors</div><div class="t mb x4a h6b y124 ff20 fs57 fcc sc0 ls1 ws61">Many enzymes require the<span class="_15 blank"> </span>presence of additional</div><div class="t mb x4a h6d y125 ff20 fs57 fcc sc0 ls5e ws62">reactive groups known as <span class="ff21 ls60 ws63">cofactors </span><span class="ls69 ws64">in order to</span></div><div class="t mb x4a h6b y126 ff20 fs57 fcc sc0 ls1 ws65">have full catalytic function. Cofactors may con-</div><div class="t mb x4a h6b y127 ff20 fs57 fcc sc0 ls5d ws66">sist of inorganic molecules such as the metal ions</div><div class="t mb x4a h6b y128 ff20 fs57 fcc sc0 ls5e ws67">of zinc, copper, manganese, magnesium, etc. In</div><div class="t mb x4a h6b y129 ff20 fs57 fcc sc0 ls60 ws68">such instances, these cofactors directly<span class="_19 blank"> </span>alter the</div><div class="t mb x4a h6b y12a ff20 fs57 fcc sc0 ls5c ws69">binding activity of the enzyme by changing the</div><div class="t mb x4a h6b y12b ff20 fs57 fcc sc0 ls5c ws6a">char<span class="_0 blank"></span>ge distribution and shape of the active site of</div><div class="t mb x4a h6b y12c ff20 fs57 fcc sc0 ls5c ws6b">the enzyme. Where cofactors are tightly bound to</div><div class="t mb x4a h6b y12d ff20 fs57 fcc sc0 ls5e ws6c">the enzyme at all times, they are referred to as</div><div class="t mb x4a h6d y12e ff21 fs57 fcc sc0 ls1 ws6d">prosthetic<span class="_22 blank"> </span>groups <span class="ff20 ls61 ws6e">, e.g. copper, manganese, zinc, </span></div><div class="t mb x4a h6b y12f ff20 fs57 fcc sc0 ls5c ws6f">biotin, vitamin B6, etc.</div><div class="t mb x0 h6b y130 ff20 fs57 fcc sc0 ls1 ws70">Alternatively, cofactors may be or<span class="_0 blank"></span>ganic</div><div class="t mb x4a h6d y131 ff20 fs57 fcc sc0 ls5e ws71">molecules known as <span class="ff21 ls62 ws72">coenzymes </span><span class="ls1 ws73">. In c<span class="_1 blank"> </span>ontrast to</span></div><div class="t mb x4a h6b y132 ff20 fs57 fcc sc0 ls5d ws74">inor<span class="_0 blank"></span>ganic cofactors, coenzymes do not alter the</div><div class="t mb x4a h6b y133 ff20 fs57 fcc sc0 ls5d ws75">enzyme\u2019s binding activity but instead act as</div><div class="t mb x4a h6b y134 ff20 fs57 fcc sc0 ls1 ws76">important compounds which directly participate</div><div class="t mb x4a h6b y135 ff20 fs57 fcc sc0 ls1 ws77">in the reaction. Coenzymes can therefore be</div><div class="t mb x1e h6b y136 ff20 fs57 fcc sc0 ls61 ws78">considered to act as<span class="_23 blank"> </span>second substrates for or</div><div class="t mb x1e h6b y137 ff20 fs57 fcc sc0 ls6a ws79">products of the reaction. For example, in the</div><div class="t mb x1e h6b y138 ff20 fs57 fcc sc0 ls1 ws7a">reaction outlined in Figure 4.6, where lactate</div><div class="t mb x1e h6b y139 ff20 fs57 fcc sc0 ls1 ws7b">is oxidized to pyruvate via the enzyme LDH,</div><div class="t mb x1e h6e y13a ff22 fs57 fcc sc0 ls6b ws7c">nicotinamide adenine dinucleotide (NAD<span class="fs58 ls63 v4">+</span><span class="ls1 v0">)</span></div><div class="t mb x1e h6b y13b ff20 fs57 fcc sc0 ls60 ws7d">acts as a coenzyme necessary for the reaction</div><div class="t mb x1e h6b y13c ff20 fs57 fcc sc0 ls1 ws5f">to proceed.</div><div class="t mb x18 h6b y13d ff20 fs57 fcc sc0 ls5c ws7e">Many of the water-soluble vitamins, especially</div><div class="t mb x1e h6b y13e ff20 fs57 fcc sc0 ls1 ws7f">the B vitamins, are precursors (i.e. form the basic</div><div class="t mb x1e h6b y13f ff20 fs57 fcc sc0 ls60 ws80">components) for coenzymes, and<span class="_9 blank"> </span>thus<span class="_9 blank"> </span>it is<span class="_9 blank"> </span>essential</div><div class="t mb x1e h6b y140 ff20 fs57 fcc sc0 ls1 ws81">that we obtain the appropriate amount of vitamin</div><div class="t mb x1e h6b y141 ff20 fs57 fcc sc0 ls60 ws82">B in our diets. Indeed, there are many diseases </div><div class="t mb x1e h6b y142 ff20 fs57 fcc sc0 ls60 ws83">associated with vitamin B de\ufb01ciency, given that</div><div class="t mb x1e h6b y143 ff20 fs57 fcc sc0 ls1 ws84">certain enzymes cannot function optimally<span class="_e blank"> </span>if they</div><div class="t mb x1e h6b y144 ff20 fs57 fcc sc0 ls60 ws85">lack the necessary<span class="_f blank"> </span>coenzyme. Members of the vita-</div><div class="t mb x1e h6b y145 ff20 fs57 fcc sc0 ls6a ws86">min B family and the coenzymes they form are</div><div class="t mb x1e h6b y146 ff20 fs57 fcc sc0 ls5e ws87">shown in T<span class="_3 blank"></span>able 4.2, as are recommended dietary</div><div class="t mb x1e h6b y147 ff20 fs57 fcc sc0 ls60 ws88">allowances (RDA) for 19<span class="_1 blank"> </span>\u2013<span class="_5 blank"> </span>30 year old males (as</div><div class="t mb x1e h6b y148 ff20 fs57 fcc sc0 ls1 ws89">recommended by the Food and Nutrition Board</div><div class="t mb x1e h6b y149 ff20 fs57 fcc sc0 ls1 ws8a">of the National Academy of Sciences). The<span class="_e blank"> </span>coen-</div><div class="t mb x1e h6f y14a ff20 fs57 fcc sc0 ls61 ws8b">zymes NAD<span class="ff23 fs58 ls64 v4">+</span><span class="ls5c ws8c v0">and F<span class="_3 blank"></span>AD are especially important</span></div><div class="t mb x1e h6b y14b ff20 fs57 fcc sc0 ls6c ws8d">for <span class="ff24 ls5c ws8e">oxidation-r<span class="_0 blank"></span>eduction<span class="_9 blank"> </span>r<span class="_3 blank"></span>eactions <span class="ff20 ls6d ws8f">,a<span class="_24 blank"></span>st<span class="_24 blank"></span>h<span class="_25 blank"></span>e<span class="_25 blank"></span>yf<span class="_24 blank"></span>o<span class="_25 blank"></span>r<span class="_24 blank"></span>mt<span class="_24 blank"></span>h<span class="_25 blank"></span>e</span></span></div><div class="t mb x1e h6b y14c ff20 fs57 fcc sc0 ls1 ws90">basis for oxidative phosphorylation, the ener<span class="_0 blank"></span>gy-</div><div class="t mb x1e h6b y14d ff20 fs57 fcc sc0 ls1 ws91">producing pathway which is dominant during<span class="_a blank"> </span>pro-</div><div class="t mb x1e h6b y14e ff20 fs57 fcc sc0 ls5d ws92">longed endurance-type exercise.</div><div class="t mb x1e h6c y14f ff1d fs57 fcb sc0 ls69 ws93">4.4.4<span class="_21 blank"> </span>Classi\ufb01cation of enzymes</div><div class="t mb x1e h6b y150 ff20 fs57 fcc sc0 ls1 ws94">As we saw in Chapter 3, there are many common</div><div class="t mb x1e h6b y151 ff20 fs57 fcc sc0 ls5c ws95">types of chemical reaction. Similarly,<span class="_a blank"> </span>the enzymes</div><div class="t mb x1e h6b y152 ff20 fs57 fcc sc0 ls5e ws96">which facilitate many of these reactions can</div><div class="t mb x1e h6b y153 ff20 fs57 fcc sc0 ls61 ws97">also be classi\ufb01ed into six common classes and</div><div class="t mb x1e h6b y154 ff20 fs57 fcc sc0 ls61 ws98">sub-classes (see T<span class="_26 blank"></span>able 4.3), as designated by</div><div class="t mb x1e h6b y155 ff20 fs57 fcc sc0 ls1 ws99">the International Union of Biochemistry. Most</div><div class="t mb x1e h6b y156 ff20 fs57 fcc sc0 ls5c ws9a">enzymes are recognizable by the suf<span class="_0 blank"></span>\ufb01x-<span class="ff24 ls65 ws9b">ase </span><span class="ls6e ws9c">,w<span class="_27 blank"></span>h<span class="_27 blank"></span>i<span class="_27 blank"></span>l<span class="_27 blank"></span>e</span></div><div class="t mb x1e h6b y157 ff20 fs57 fcc sc0 ls6a ws9d">the \ufb01rst part of the enzyme\u2019s name (everything</div><div class="t mb x1e h6b y158 ff20 fs57 fcc sc0 ls1 ws9e">that precedes the suf<span class="_0 blank"></span>\ufb01x) usually refers to the type</div><div class="t mb x1e h6b y159 ff20 fs57 fcc sc0 ls5c ws9f">of reaction and/or the substrate which they act</div><div class="t mb x1e h6b y15a ff20 fs57 fcc sc0 ls1 wsa0">upon. For example, the enzyme creatine kinase</div><div class="t mb x1e h6b y15b ff20 fs57 fcc sc0 ls1 wsa1">has phosphocreatine (PCr) as its substrate and,</div><div class="t mb x1e h6b y15c ff20 fs57 fcc sc0 ls1 wsa2">as a kinase, it transfers a phosphate group to</div><div class="t mb x1e h6b y15d ff20 fs57 fcc sc0 ls1 wsa3">ADP, thus making the products A<span class="_1e blank"></span>TP and creatine</div><div class="t mb x1e h6b y15e ff20 fs57 fcc sc0 ls69 wsa4">(Cr). This reaction is highly active within the</div><div class="t mb x1e h6b y15f ff20 fs57 fcc sc0 ls1 wsa5">\ufb01rst 10 seconds<span class="_19 blank"> </span>of maximal<span class="_19 blank"> </span>exercise, providing</div><div class="t mb x1e h6b y160 ff20 fs57 fcc sc0 ls6f wsa6">ar<span class="_28 blank"></span>a<span class="_28 blank"></span>p<span class="_28 blank"></span>i<span class="_28 blank"></span>ds<span class="_28 blank"></span>o<span class="_29 blank"></span>u<span class="_28 blank"></span>r<span class="_28 blank"></span>c<span class="_28 blank"></span>eo<span class="_28 blank"></span>fA<span class="_2a blank"></span>T<span class="_28 blank"></span>Pp<span class="_28 blank"></span>r<span class="_28 blank"></span>o<span class="_28 blank"></span>d<span class="_28 blank"></span>u<span class="_28 blank"></span>c<span class="_29 blank"></span>t<span class="_28 blank"></span>i<span class="_28 blank"></span>o<span class="_28 blank"></span>nt<span class="_28 blank"></span>of<span class="_28 blank"></span>u<span class="_29 blank"></span>e<span class="_28 blank"></span>lm<span class="_28 blank"></span>u<span class="_28 blank"></span>s<span class="_28 blank"></span>c<span class="_28 blank"></span>l<span class="_28 blank"></span>e</div><div class="t mb x1e h6b y161 ff20 fs57 fcc sc0 ls70 wsa7">contraction (Parolin <span class="ff24 ls62 wsa8">et<span class="_a blank"> </span>al </span><span class="ls71 wsa9">.1<span class="_2b blank"></span>9<span class="_2b blank"></span>9<span class="_2b blank"></span>9<span class="_2b blank"></span>)<span class="_27 blank"></span>.</span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x6d h10 y162 ff2 fsc fc3 sc0 ls50 wsaa">MacLaren <span class="ls1e wsb">D, </span><span class="wsab">Morton <span class="ls72 wsb">J. <span class="ls23 ws1d">Biochemistry </span><span class="ls73">for <span class="ls28 wsac">Sport <span class="ls25 ws20">and </span></span><span class="ls1f">Exercise </span></span></span><span class="wsad">Metabolism<span class="ls26 wsb">. <span class="ls27 wsae">Wiley<span class="ls1 ws2e">-<span class="ls23 wsaf">Blackwell</span></span></span>. Oxford; 2012</span></span></span></div><div class="t m1 x6e h70 y163 ff1 fs3 fc0 sc0 ls74 wsb">Concentração do Subst<span class="_1 blank"> </span>rato</div><div class="t m42 x6f h70 y164 ff1 fs3 fc0 sc0 ls75 wsb">Ta<span class="_6 blank"> </span>x<span class="_6 blank"> </span>a<span class="_8 blank"> </span> <span class="_6 blank"> </span>d<span class="_6 blank"> </span>a<span class="_8 blank"> </span> <span class="_6 blank"> </span>R<span class="_6 blank"> </span>e<span class="_6 blank"> </span>a<span class="_8 blank"> </span>ç<span class="_6 blank"> </span>ã<span class="_8 blank"> </span>o</div></div><div class="c x3 yc w2 h4"><div class="t m1 x36 ha y165 ff4 fs7 fc0 sc0 ls1 wsb0">C<span class="fs59 ls76 wsb1">OF<span class="_3 blank"></span>ACTORES</span></div><div class="t m1 x70 h71 y166 ff4 fs3 fc1 sc0 ls1 wsb2">Algumas enzimas necessitam <span class="ls77 wsb">de </span><span class="ws46">cofactores para funcionar</span></div><div class="t m1 x71 h71 y167 ff4 fs3 fc1 sc0 ls1 wsb3">Orgânicos</div><div class="t m1 x72 h71 y168 ff4 fs3 fc1 sc0 ls1 wsb3">(Coenzima)</div><div class="t m1 x5b h71 y167 ff4 fs3 fc1 sc0 ls1 wsb3">Inorgânicos</div><div class="t m1 x21 h72 y169 ff2 fs14 fc0 sc0 ls78 wsb4">Vitam<span class="_0 blank"></span>inas <span class="ls43 wsb">e <span class="ls79 wsb5">derivados</span></span></div><div class="t m1 x73 h72 y16a ff2 fs14 fc0 sc0 ls7a wsb6">Magnésio</div><div class="t m1 x3b h72 y16b ff2 fs14 fc0 sc0 ls7b wsb7">Zinco</div><div class="t m1 x3b h72 y16c ff2 fs14 fc0 sc0 ls7c wsb8">Ferro</div><div class="t m1 x74 h72 y16d ff2 fs14 fc0 sc0 ls52 wsb9">Cobre</div><div class="t m1 x75 h72 y16e ff2 fs14 fc0 sc0 ls7a wsb6">Manganês</div><div class="t m1 x6b h72 y16f ff2 fs14 fc0 sc0 ls7d wsba">Selénio</div><div class="t m1 x76 h73 y170 ff2 fsa fc3 sc0 ls1b wsb">De <span class="ls7e wsbb">Ve l o s o<span class="_10 blank"> </span></span><span class="ls7f">S, com <span class="ls80 wsbc">permissão</span></span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf7" class="pf w0 h0" data-page-no="7"><div class="pc pc7 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg7.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">7</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x12 hf y16 ff4 fs1 fc0 sc0 ls1 ws17">P<span class="fsb ls1c ws18">ÉPTIDO</span>/P<span class="fsb ls1d ws19">ROTEÍNA</span></div><div class="t m1 x77 hb y171 ff4 fs8 fc0 sc0 ls81">P<span class="fs7 ls86 wsbd">ROTEÍNAS </span><span class="ls1 wsbe">H</span><span class="fs7 ls82 wsbf">UMANAS <span class="ls87 wsc0">SÃO COMPOST<span class="_26 blank"></span>AS POR <span class="fs8 ls83 wsb">21 <span class="_3 blank"></span>AA</span></span></span></div><div class="t m1 x13 h10 y17 ff2 fsc fc3 sc0 ls1e ws1a">Newsholme <span class="ls1f wsb">E, <span class="ls20 ws1b">Leech </span><span class="ls21">A. <span class="ls22 ws1c">Functional <span class="ls23 ws1d">Biochemistry <span class="ls24 ws1e">in </span></span></span></span></span><span class="ws1f">Health <span class="ls25 ws20">and </span><span class="ws21">Disease<span class="ls26 wsb">. John </span></span><span class="ls27">Wiley <span class="ls28 wsb">& <span class="_0 blank"></span>Sons; 2011<span class="ls26">. </span></span></span></span></div></div><div class="c x3 yc w2 h4"><div class="t m1 x46 h21 y172 ff4 fs6 fc7 sc0 ls1 ws34">D<span class="fs8 ls88 wsc1">IGES<span class="_0 blank"></span>TÃO <span class="ls84">E<span class="fs6 ls85">A</span><span class="ls89 wsc2">BSORÇÃO<span class="_22 blank"> </span>DE <span class="fs6 ls85">A</span><span class="ls8a wsc3">MI NO Á CI D OS<span class="_1a blank"> </span><span class="ls1">E</span></span></span></span></span></div><div class="t m1 x9 h21 y173 ff4 fs6 fc7 sc0 ls1 ws34">P<span class="fs8 ls8b wsc4">ÉPTIDOS</span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf8" class="pf w0 h0" data-page-no="8"><div class="pc pc8 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg8.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">8</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x15 h74 y174 ff25 fsa fc0 sc0 ls8f wsc5">Lúmen</div><div class="t m1 x15 h74 y175 ff25 fsa fc0 sc0 ls90 wsc6">int<span class="_0 blank"></span>es<span class="_0 blank"></span>tin<span class="_0 blank"></span>a<span class="_0 blank"></span>l</div><div class="t m1 x15 h74 y176 ff25 fsa fc0 sc0 ls91 wsc7">Enter ó ci<span class="_1 blank"> </span>t os</div><div class="t m1 x78 h74 y177 ff25 fsa fc0 sc0 ls91 wsc8">Pla sma</div><div class="t m1 x79 h72 y178 ff2 fs14 fc9 sc0 ls92 wsc9">Prote<span class="ls8c">í<span class="ls44 wsca">nas <span class="fsa fc2 ls93 wsb v5">Amino Ácidos<span class="_2c blank"> </span><span class="ls1b wscb">Di<span class="ls1 wscc">-<span class="ls93 wscd">Péptidos</span></span></span></span></span></span></div><div class="t m1 x51 h75 y179 ff25 fs59 fc0 sc0 ls1">+</div><div class="t m1 x2e h73 y17a ff2 fsa fc2 sc0 ls94 wsce">Tr i <span class="ls1 wscc">-<span class="ls93 wscd">Péptidos</span></span></div><div class="t m1 x17 h75 y17b ff25 fs59 fc0 sc0 ls1">+</div><div class="t m1 x7a h76 y17c ff2 fs5a fc9 sc0 ls95 wscf">Péptidos <span class="lsc wsd0">com<span class="_0 blank"></span>plexos</span></div><div class="t m1 x7b h75 y17b ff25 fs59 fc0 sc0 ls1">+</div><div class="t m1 x5 h77 y17d ff4 fs5b fcd sc0 ls1 wsd1">Não <span class="ls96 wsb">se </span><span class="wsd2">absorvem<span class="_2d blank"> </span><span class="ff5 fs59 fc0 ls8d v6">A<span class="fs5b ls8e wsd3">BSORÇÃO</span></span></span></div><div class="t m1 x72 h21 y17e ff4 fs6 fc2 sc0 ls1 ws34">D<span class="fs8 ls88 wsc1">IGES<span class="_0 blank"></span>TÃO <span class="ls84">E<span class="fs6 ls85">A</span><span class="ls89 wsd4">BSORÇÃO</span></span></span></div><div class="t m1 x7c h74 y17f ff25 fsa fc7 sc0 ls97 wsd5">Transpor t e<span class="_8 blank"> </span><span class="ls8f wsd6">par a<span class="_8 blank"> </span>os</span></div><div class="t m1 x7c h74 y180 ff25 fsa fc7 sc0 ls98 wsd7">Órg ã o s</div><div class="t m1 x7d h1d y181 ff4 fs14 fcd sc0 ls1 ws2a">Degradação</div><div class="t m1 x7d h1d y182 ff4 fs14 fcd sc0 ls1 ws2a">bacteriana</div><div class="t m1 x12 h78 y183 ff4 fs5a fce sc0 ls1 wsd8">Proteases</div><div class="t m1 x12 h79 y184 ff5 fs5a fc0 sc0 ls99 wsd9">Digestão</div><div class="t m1 x7e h7a y185 ff4 fs5b fcd sc0 ls1 wsd1">Não <span class="ls96 wsb">se </span><span class="wsd2">absorvem</span></div><div class="t m1 x6d h10 y186 ff2 fsc fcf sc0 ls28 wsb">Smith JL, <span class="ls9a wsda">Gropper </span>SS.<span class="_0 blank"></span> <span class="ls21 wsdb">Advanced <span class="ls1e wsdc">Nutrition <span class="ls25 ws20">and </span><span class="ws1f">Human <span class="ls50 wsdd">Metabolism <span class="ls1 ws2e">5<span class="fs5c ls9b wsde v5">th </span><span class="ls1f wsdf">Edition</span></span></span></span></span></span><span class="ls26">. <span class="ls27 wsae">Wiley<span class="ls1 ws2e">-<span class="ls23 wsaf">Blackwell</span></span></span>; 2009. </span></div></div><div class="c x3 yc w2 h4"><div class="t m1 x27 h10 yd2 ff2 fsc fc3 sc0 ls1e wse0">Untersmayr <span class="ls1f wsb">E, <span class="ls72 wse1">Jensen<span class="ls1 ws2e">-</span><span class="wse2">Jarolim </span></span>E. <span class="ls72 wsdc">Journa<span class="_0 blank"></span>l <span class="ls22 wsdd">of <span class="ls21 wse3">Allergy <span class="ls25 ws20">and <span class="ls1e wsda">Clinical <span class="ls26 wsb">Immunology. 2008 Jun;121(6):1301<span class="ls1 ws2e">\u2013</span><span class="ls25">8. </span></span></span></span></span></span></span></span></div></div><div class="c x7f y187 w7 h7b"><div class="t m43 x80 h7c y188 ff26 fs5d fc0 sc0 ls1 wse4">time points of <span class="ff27 wse5">in vitr<span class="_3 blank"></span>o<span class="_a blank"> </span><span class="ff26 wse6">digestion in a patie<span class="_0 blank"></span>nt with gras<span class="_0 blank"></span>s pollen</span></span></div><div class="t m43 x81 h7c y189 ff26 fs5d fc0 sc0 ls1 wse7">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_0 blank"></span>wed th<span class="_0 blank"></span>at gastri<span class="_0 blank"></span>c dige<span class="_0 blank"></span>stion sub<span class="_0 blank"></span>stan<span class="_0 blank"></span>tially</div><div class="t m43 x82 h7c y18a ff26 fs5d fc0 sc0 ls1 wse8">decreas<span class="_0 blank"></span>ed the aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>nic capacity of the<span class="_0 blank"></span>se cross<span class="_0 blank"></span>-reacti<span class="_3 blank"></span>ve food</div><div class="t m43 x83 h7c y18b ff26 fs5d fc0 sc0 ls1 wse9">protein<span class="_0 blank"></span>s (<span class="fc10 wsea">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n testin<span class="_0 blank"></span>g in<span class="_a blank"> </span>pat<span class="_0 blank"></span>ients wit<span class="_0 blank"></span>h \ufb01<span class="_0 blank"></span>sh all<span class="_0 blank"></span>ergy<span class="_a blank"> </span>wit<span class="_0 blank"></span>h</span></span></div><div class="t m43 x84 h7c y18c ff26 fs5d fc0 sc0 ls1 wseb">SGF-p<span class="_0 blank"></span>redige<span class="_0 blank"></span>sted or SGF-u<span class="_0 blank"></span>ndi<span class="_0 blank"></span>gested co<span class="_0 blank"></span>d\ufb01sh all<span class="_0 blank"></span>erge<span class="_0 blank"></span>ns sho<span class="_3 blank"></span>wed a</div><div class="t m43 x85 h7c y18d ff26 fs5d fc0 sc0 ls1 wsec">signi\ufb01<span class="_0 blank"></span>can<span class="_0 blank"></span>t diges<span class="_0 blank"></span>tion tim<span class="_0 blank"></span>e-d<span class="_0 blank"></span>epende<span class="_0 blank"></span>nt redu<span class="_0 blank"></span>cti<span class="_0 blank"></span>on of<span class="_9 blank"> </span>induce<span class="_0 blank"></span>d wheal</div><div class="t m43 x86 h7c y18e ff26 fs5d fc0 sc0 ls1 wsed">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>v<span class="_0 blank"></span>er<span class="_0 blank"></span>, double<span class="_0 blank"></span>-blin<span class="_0 blank"></span>d, place<span class="_0 blank"></span>bo-co<span class="_0 blank"></span>ntroll<span class="_0 blank"></span>ed, food</div><div class="t m43 x87 h7c y18f ff26 fs5d fc0 sc0 ls1 wsee">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tients wit<span class="_0 blank"></span>h \ufb01sh all<span class="_0 blank"></span>ergy<span class="_9 blank"> </span>res<span class="_0 blank"></span>ulted in a 10- to</div><div class="t m43 x88 h7c y190 ff26 fs5d fc0 sc0 ls1 wsef">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ated all<span class="_0 blank"></span>ergen dos<span class="_0 blank"></span>e if the \ufb01sh prot<span class="_0 blank"></span>eins were pre-</div><div class="t m43 x89 h7c y191 ff26 fs5d fc0 sc0 ls1 wsf0">viousl<span class="_0 blank"></span>y subjected to <span class="ff27 wsf1">in vit<span class="_0 blank"></span>r<span class="_3 blank"></span>o<span class="_f blank"> </span><span class="ff26 wsf2">gastric dige<span class="_0 blank"></span>stion.</span></span></div><div class="t m44 x8a h7d y192 ff26 fs5e fc10 sc0 ls1">27</div><div class="t m43 x8b h7e y193 ff28 fs5f fc0 sc0 ls1 wsf3">SAFETY<span class="_a blank"> </span>ISSUES<span class="_17 blank"> </span>AND<span class="_a blank"> </span>CLINICAL<span class="_17 blank"> </span>IMPLICATIONS</div><div class="t m43 x8c h7e y194 ff28 fs5f fc0 sc0 ls1 wsf4">FOR<span class="_17 blank"> </span>ALLERG IC<span class="_a blank"> </span>AND<span class="_17 blank"> </span>NONALLER GIC<span class="_a blank"> </span>CONSUMERS</div><div class="t m43 x8d h7c y195 ff26 fs5d fc0 sc0 ls1 wsf5">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m43 x8e h7c y196 ff26 fs5d fc0 sc0 ls1 wsf6">clinical outcome after the consumption of<span class="_a blank"> </span>a digestion-sensitiv<span class="_0 blank"></span>e</div><div class="t m43 x8f h7c y197 ff26 fs5d fc0 sc0 ls1 wsf7">dietary protein depends to a certain<span class="_10 blank"> </span>degree on the gastric digestiv<span class="_0 blank"></span>e</div><div class="t m43 x90 h7c y198 ff26 fs5d fc0 sc0 ls1 wsf8">capacity<span class="_3 blank"></span>. If the food protein is<span class="_f blank"> </span>exposed to gastric enzymes during</div><div class="t m43 x8d h7c y199 ff26 fs5d fc0 sc0 ls1 wsf9">transit, protein cleavage takes place, inducing either oral toler-</div><div class="t m43 x91 h7c y19a ff26 fs5d fc0 sc0 ls1 wsfa">ance or immune ignorance toward the ingested food protein.</div><div class="t m43 x92 h7c y19b ff26 fs5d fc0 sc0 ls1 wsfb">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m43 x93 h7c y19c ff26 fs5d fc0 sc0 ls1 wsfc">impaired digestion, such as during acid-suppression treatment,</div><div class="t m43 x94 h7c y19d ff26 fs5d fc0 sc0 ls1 wsfd">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m43 x95 h7c y19e ff26 fs5d fc0 sc0 ls1 wsfe">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m43 x96 h7c y19f ff26 fs5d fc0 sc0 ls1 wsff">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m43 x97 h7c y1a0 ff26 fs5d fc0 sc0 ls1 ws100">the allergenic capacity<span class="_9 blank"> </span>of ingested food<span class="_9 blank"> </span>proteins, whereas severe</div><div class="t m43 x98 h7c y1a1 ff26 fs5d fc0 sc0 ls1 ws101">allergic reactions at much lower amounts of ingested food</div><div class="t m43 x99 h7c y1a2 ff26 fs5d fc0 sc0 ls1 ws102">proteins could occur if digestion is impaired (<span class="_1 blank"> </span><span class="fc10 ws103">Fig 3</span>).</div><div class="t m43 x9a h7c y1a3 ff26 fs5d fc0 sc0 ls1 ws104">The revie<span class="_0 blank"></span>wed data<span class="_a blank"> </span>indicate<span class="_a blank"> </span>that<span class="_18 blank"> </span>the current<span class="_a blank"> </span>concept<span class="_a blank"> </span>of food</div><div class="t m43 x9b h7c y1a4 ff26 fs5d fc0 sc0 ls1 ws105">allergen classi\ufb01cation into class 1<span class="_f blank"> </span>(true food allergen) and<span class="_f blank"> </span>class 2</div><div class="t m43 x9c h7c y1a5 ff26 fs5d fc0 sc0 ls1 ws106">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m43 x9d h7c y1a6 ff26 fs5d fc0 sc0 ls1 ws107">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m43 x9a h7c y1a7 ff26 fs5d fc0 sc0 ls1 ws108">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m43 x4a h7c y1a8 ff26 fs5d fc0 sc0 ls1 ws109">and<span class="_10 blank"> </span>consumers\u2019 safety<span class="_f blank"> </span>might<span class="_10 blank"> </span>be<span class="_f blank"> </span>en<span class="_0 blank"></span>visaged<span class="_10 blank"> </span>(<span class="fc10 ws10a">T<span class="_3 blank"></span>able II<span class="fc0 ws10b">). It should be</span></span></div><div class="t m43 x9e h7f y1a9 ff28 fs60 fc0 sc0 ls1 ws10c">FIG 3.<span class="_a blank"> </span><span class="ff29 ws10d">The gate-keeping function of the stomach in the sensitization and</span></div><div class="t m43 x9f h7f y1aa ff29 fs60 fc0 sc0 ls1 ws10e">effector phase of food allergy. The fate of a dietary protein<span class="_10 blank"> </span>depends<span class="_f blank"> </span>on the</div><div class="t m43 xa0 h7f y1ab ff29 fs60 fc0 sc0 ls1 ws10f">gastric<span class="_a blank"> </span>digestive<span class="_a blank"> </span>function<span class="_17 blank"> </span>mainly<span class="_a blank"> </span>accomplished<span class="_a blank"> </span>by<span class="_a blank"> </span>the<span class="_17 blank"> </span>gastric<span class="_a blank"> </span>protease</div><div class="t m43 xa1 h7f y1ac ff29 fs60 fc0 sc0 ls1 ws110">pepsin. If the protein<span class="_17 blank"> </span>structure is destroyed beca<span class="_1 blank"> </span>use of proteolysis, oral</div><div class="t m43 xa2 h7f y1ad ff29 fs60 fc0 sc0 ls1 ws111">tolerance<span class="_8 blank"> </span>or<span class="_8 blank"> </span>immune<span class="_8 blank"> </span>ignorance<span class="_8 blank"> </span>and<span class="_8 blank"> </span>a<span class="_8 blank"> </span>reduce d<span class="_8 blank"> </span>allerge nic<span class="_10 blank"> </span>potential<span class="_6 blank"> </span>might<span class="_8 blank"> </span>be</div><div class="t m43 xa3 h7f y1ae ff29 fs60 fc0 sc0 ls1 ws112">the<span class="_22 blank"> </span>result.<span class="_22 blank"> </span>However,<span class="_2e blank"> </span>when<span class="_2e blank"> </span>gastric<span class="_22 blank"> </span>digestion<span class="_22 blank"> </span>is<span class="_2e blank"> </span>imp aired<span class="_22 blank"> </span>(eg,<span class="_22 blank"> </span>under</div><div class="t m43 xa4 h7f y1af ff29 fs60 fc0 sc0 ls1 ws113">hypoacidic<span class="_f blank"> </span>gastric<span class="_f blank"> </span>conditions),<span class="_f blank"> </span>digestion-labile<span class="_f blank"> </span>proteins<span class="_f blank"> </span>might<span class="_f blank"> </span>trigger<span class="_f blank"> </span>oral</div><div class="t m43 xa5 h7f y1b0 ff29 fs60 fc0 sc0 ls1 ws114">sensitization or severe allergic symptoms<span class="_9 blank"> </span>in a previousl<span class="_1 blank"> </span>y sensitized indi-</div><div class="t m43 xa6 h7f y1b1 ff29 fs60 fc0 sc0 ls1 ws115">vidual.<span class="_17 blank"> </span>The<span class="_17 blank"> </span>\ufb01gure<span class="_17 blank"> </span>was<span class="_17 blank"> </span>created<span class="_a blank"> </span>with<span class="_17 blank"> </span>the<span class="_17 blank"> </span>structural<span class="_17 blank"> </span>information<span class="_17 blank"> </span>provided</div><div class="t m43 xa7 h7f y1b2 ff29 fs60 fc0 sc0 ls1 ws116">from<span class="_a blank"> </span>Research<span class="_a blank"> </span>Collaboratory<span class="_a blank"> </span>for<span class="_a blank"> </span>Structural<span class="_a blank"> </span>Bioinformatics<span class="_a blank"> </span>Protein<span class="_a blank"> </span>Data</div><div class="t m43 xa8 h7f y1b3 ff29 fs60 fc0 sc0 ls1 ws116">Bank<span class="_10 blank"> </span>accession<span class="_f blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_10 blank"> </span>and<span class="_f blank"> </span>5PEP.</div><div class="t m43 xa9 h7f y1b4 ff28 fs60 fc0 sc0 ls1 ws117">FIG<span class="_18 blank"> </span>2. <span class="ff29 ws111">Reduced<span class="_e blank"> </span>allergenicity<span class="_e blank"> </span>of<span class="_18 blank"> </span>melo n<span class="_e blank"> </span>allergens<span class="_e blank"> </span>after<span class="_18 blank"> </span>incubation<span class="_e blank"> </span>with</span></div><div class="t m43 xaa h7f y1b5 ff29 fs60 fc0 sc0 ls1 ws118">gastric enzymes. After subjection to<span class="_10 blank"> </span>SGF, melon allergens induc<span class="_1 blank"> </span>e a smaller</div><div class="t m43 xab h7f y1b6 ff29 fs60 fc0 sc0 ls1 ws119">wheal reaction in a patient with melon<span class="_17 blank"> </span>allergy compared with the undi-</div><div class="t m43 xac h7f y1b7 ff29 fs60 fc0 sc0 ls1 ws11a">gested<span class="_a blank"> </span>extract.<span class="_18 blank"> </span>The<span class="_a blank"> </span>alteration<span class="_a blank"> </span>of<span class="_18 blank"> </span>skin<span class="_a blank"> </span>reactivity<span class="_a blank"> </span>was<span class="_a blank"> </span>dependen t<span class="_18 blank"> </span>on<span class="_a blank"> </span>the</div><div class="t m43 xad h7f y1b8 ff29 fs60 fc0 sc0 ls1 ws11b">incubation<span class="_f blank"> </span>time<span class="_10 blank"> </span>with<span class="_f blank"> </span>the<span class="_10 blank"> </span>proteolytic<span class="_f blank"> </span>enzymes.</div><div class="t m43 xae h80 y1b9 ff28 fs61 fc0 sc0 ls1 ws11c">TABLE II. <span class="ff29 ws11d">Key concepts and<span class="_9 blank"> </span>safety implications</span></div><div class="t m43 xaf h81 y1ba ff26 fs61 fc0 sc0 ls1 ws11e">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m43 xb0 h81 y1bb ff26 fs61 fc0 sc0 ls1 ws11f">safety tests for novel (eg, genetically modi\ufb01ed) food compounds.</div><div class="t m43 xb1 h81 y1bc ff26 fs61 fc0 sc0 ls1 ws120">Patients should be advised that<span class="_9 blank"> </span>threshold levels might vary in situations of</div><div class="t m43 xb2 h81 y1bd ff26 fs61 fc0 sc0 ls1 ws121">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current efforts to</div><div class="t m43 xb3 h81 y1be ff26 fs61 fc0 sc0 ls1 ws122">de\ufb01ne no-observed-adv<span class="_0 blank"></span>erse-ef<span class="_0 blank"></span>fect lev<span class="_0 blank"></span>els for food allergens.</div><div class="t m43 xb4 h81 y1bf ff26 fs61 fc0 sc0 ls1 ws123">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m43 xb5 h81 y1c0 ff26 fs61 fc0 sc0 ls1 ws122">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m43 xb6 h81 y1c1 ff26 fs61 fc0 sc0 ls1 ws124">food ingestion.</div><div class="t m43 xb7 h82 y1c2 ff29 fs62 fc0 sc0 ls1 ws125">J ALLERGY CLIN IMMUNOL</div><div class="t m43 xb8 h82 y1c3 ff29 fs62 fc0 sc0 ls1 ws126">VOLUME 121, NUMBER 6</div><div class="t m43 x9f h80 y1c4 ff29 fs61 fc0 sc0 ls1 ws127">UNTERSMAYR AND JENSEN-JAROLIM<span class="_a blank"> </span><span class="ff28">1305</span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pf9" class="pf w0 h0" data-page-no="9"><div class="pc pc9 w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bg9.png"><div class="c x0 y1 w1 h1"><div class="t m0 x1 h2 y2 ff1 fs0 fc0 sc0 ls1">9</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x27 h10 yd2 ff2 fsc fc3 sc0 ls1e wse0">Untersmayr <span class="ls1f wsb">E, <span class="ls72 wse1">Jensen<span class="ls1 ws2e">-</span><span class="wse2">Jarolim </span></span>E. <span class="ls72 wsdc">Journa<span class="_0 blank"></span>l <span class="ls22 wsdd">of <span class="ls21 wse3">Allergy <span class="ls25 ws20">and <span class="ls1e wsda">Clinical <span class="ls26 wsb">Immunology. 2008 Jun;121(6):1301<span class="ls1 ws2e">\u2013</span><span class="ls25">8. </span></span></span></span></span></span></span></span></div></div><div class="c x8 y1c5 w8 h83"><div class="t m45 xa7 h84 y1c6 ff2a fs63 fc0 sc0 ls1 ws128">For classi<span class="_0 blank"></span>\ufb01<span class="_0 blank"></span>cation pur<span class="_0 blank"></span>poses<span class="_0 blank"></span>, food aller<span class="_0 blank"></span>gens ha<span class="_0 blank"></span>ve bee<span class="_0 blank"></span>n divi<span class="_0 blank"></span>ded in</div><div class="t m45 xa3 h84 y1c7 ff2a fs63 fc0 sc0 ls1 ws129">2 classes based on th<span class="_0 blank"></span>eir poten<span class="_0 blank"></span>tial to trigg<span class="_0 blank"></span>er speci\ufb01<span class="_3 blank"></span>c<span class="_9 blank"> </span>IgE ant<span class="_0 blank"></span>ibody</div><div class="t m45 xa3 h84 y1c8 ff2a fs63 fc0 sc0 ls1 ws12a">forma<span class="_0 blank"></span>tion. Th<span class="_0 blank"></span>e comple<span class="_0 blank"></span>te or class<span class="_f blank"> </span>1 allerge<span class="_0 blank"></span>ns not onl<span class="_0 blank"></span>y cross-<span class="_0 blank"></span>link</div><div class="t m45 xa3 h84 y1c9 ff2a fs63 fc0 sc0 ls1 ws12b">IgE but are<span class="_7 blank"> </span>also the prima<span class="_0 blank"></span>ry sourc<span class="_0 blank"></span>e of sensi<span class="_0 blank"></span>tizati<span class="_0 blank"></span>on. The<span class="_0 blank"></span>se aller<span class="_0 blank"></span>gens</div><div class="t m45 xa3 h84 y1ca ff2a fs63 fc0 sc0 ls1 ws12c">are descr<span class="_0 blank"></span>ibed as<span class="_9 blank"> </span>resist<span class="_0 blank"></span>ant to th<span class="_0 blank"></span>e denatu<span class="_0 blank"></span>ratin<span class="_0 blank"></span>g condit<span class="_0 blank"></span>ions of<span class="_9 blank"> </span>fo<span class="_0 blank"></span>od</div><div class="t m45 xa3 h84 y1cb ff2a fs63 fc0 sc0 ls1 ws12d">process<span class="_0 blank"></span>ing or of enzyma<span class="_0 blank"></span>tic dig<span class="_0 blank"></span>estio<span class="_0 blank"></span>n in the gas<span class="_0 blank"></span>troint<span class="_0 blank"></span>estin<span class="_0 blank"></span>al trans<span class="_0 blank"></span>it,</div><div class="t m45 xa3 h84 y1cc ff2a fs63 fc0 sc0 ls1 ws12e">thereby ena<span class="_0 blank"></span>bli<span class="_0 blank"></span>ng direct oral se<span class="_0 blank"></span>nsitiz<span class="_0 blank"></span>ation.</div><div class="t m46 x28 h85 y1cd ff2a fs64 fc10 sc0 ls1">56</div><div class="t m45 x25 h84 y1ce ff2a fs63 fc0 sc0 ls1 ws12f">Promi<span class="_0 blank"></span>nent e<span class="_0 blank"></span>xample<span class="_0 blank"></span>s</div><div class="t m45 xa3 h84 y1cf ff2a fs63 fc0 sc0 ls1 ws130">for these cla<span class="_0 blank"></span>ss 1 allerge<span class="_0 blank"></span>ns are <span class="ff2b ls9c">b</span><span class="ws131">-lact<span class="_0 blank"></span>oglob<span class="_0 blank"></span>ulin in co<span class="_3 blank"></span>w\u2019<span class="_0 blank"></span>s milk and</span></div><div class="t m45 xa3 h84 y1d0 ff2a fs63 fc0 sc0 ls1 ws132">stable peanut pro<span class="_0 blank"></span>teins.</div><div class="t m46 x78 h85 y1d1 ff2a fs64 fc10 sc0 ls1 ws133">57,58</div><div class="t m45 x77 h84 y1d2 ff2a fs63 fc0 sc0 ls1 ws134">In contr<span class="_0 blank"></span>ast, the cla<span class="_0 blank"></span>ss 2 or incomp<span class="_0 blank"></span>lete</div><div class="t m45 xa3 h84 y1d3 ff2a fs63 fc0 sc0 ls1 ws135">food all<span class="_0 blank"></span>erge<span class="_0 blank"></span>ns are pos<span class="_0 blank"></span>tulate<span class="_0 blank"></span>d to lack se<span class="_0 blank"></span>nsitiz<span class="_0 blank"></span>ing cap<span class="_0 blank"></span>acity<span class="_26 blank"></span>.<span class="_17 blank"> </span>Thes<span class="_0 blank"></span>e</div><div class="t m45 xa3 h84 y1d4 ff2a fs63 fc0 sc0 ls1 ws136">protein<span class="_0 blank"></span>s ha<span class="_0 blank"></span>ve th<span class="_0 blank"></span>e poten<span class="_0 blank"></span>tial to<span class="_f blank"> </span>elicit<span class="_f blank"> </span>sympto<span class="_0 blank"></span>ms onl<span class="_0 blank"></span>y aft<span class="_0 blank"></span>er prima<span class="_0 blank"></span>ry</div><div class="t m45 xa3 h84 y1d5 ff2a fs63 fc0 sc0 ls1 ws137">sensi<span class="_0 blank"></span>tizati<span class="_0 blank"></span>on with cross-<span class="_0 blank"></span>react<span class="_0 blank"></span>i<span class="_0 blank"></span>ve inh<span class="_0 blank"></span>alati<span class="_0 blank"></span>v<span class="_0 blank"></span>e aller<span class="_0 blank"></span>gen<span class="_0 blank"></span>s and were</div><div class="t m45 xa3 h84 y1d6 ff2a fs63 fc0 sc0 ls1 ws138">therefo<span class="_0 blank"></span>re terme<span class="_0 blank"></span>d <span class="ff2c ws139">nonse<span class="_0 blank"></span>nsitiz<span class="_0 blank"></span>ing elici<span class="_0 blank"></span>tors<span class="ff2a">.</span></span></div><div class="t m46 xb9 h85 y1d7 ff2a fs64 fc10 sc0 ls1">59</div><div class="t m45 x32 h84 y1d8 ff2a fs63 fc0 sc0 ls1 ws13a">Promin<span class="_0 blank"></span>ent exam<span class="_0 blank"></span>ple<span class="_0 blank"></span>s</div><div class="t m45 xa3 h84 y1d9 ff2a fs63 fc0 sc0 ls1 ws13b">are protein hom<span class="_0 blank"></span>olo<span class="_0 blank"></span>gues of Bet v 1, the major birch pol<span class="_0 blank"></span>len aller<span class="_3 blank"></span>gen,</div><div class="t m45 xa3 h84 y1da ff2a fs63 fc0 sc0 ls1 ws13c">which ar<span class="_0 blank"></span>e present in fr<span class="_0 blank"></span>uits and v<span class="_0 blank"></span>e<span class="_0 blank"></span>getables<span class="_0 blank"></span>, suc<span class="_0 blank"></span>h as apple, pe<span class="_0 blank"></span>ar<span class="_0 blank"></span>, apr<span class="_0 blank"></span>i-</div><div class="t m45 xa3 h84 y1db ff2a fs63 fc0 sc0 ls1 ws13d">cot, and cherry<span class="_3 blank"></span>. Their susce<span class="_0 blank"></span>ptibil<span class="_0 blank"></span>ity to peptic dig<span class="_0 blank"></span>estio<span class="_0 blank"></span>n has been</div><div class="t m45 xa3 h84 y1dc ff2a fs63 fc0 sc0 ls1 ws13e">demonstr<span class="_0 blank"></span>ate<span class="_0 blank"></span>d</div><div class="t m46 xba h85 y1dd ff2a fs64 fc10 sc0 ls1 ws133">60,61</div><div class="t m45 x9c h84 y1de ff2a fs63 fc0 sc0 ls1 ws13f">and might e<span class="_0 blank"></span>xplain why mos<span class="_0 blank"></span>t often local b<span class="_0 blank"></span>ut</div><div class="t m45 xa3 h84 y1df ff2a fs63 fc0 sc0 ls1 ws140">not syste<span class="_0 blank"></span>mic sympto<span class="_0 blank"></span>ms are trigg<span class="_0 blank"></span>ered on inge<span class="_0 blank"></span>sti<span class="_0 blank"></span>on of Bet v 1 homo-</div><div class="t m45 xa3 h84 y1e0 ff2a fs63 fc0 sc0 ls1 ws141">logues<span class="_0 blank"></span>. Only st<span class="_0 blank"></span>abiliz<span class="_0 blank"></span>ation of<span class="_8 blank"> </span>a Bet v 1 epitope in<span class="_8 blank"> </span>a mimotope con-</div><div class="t m45 xa3 h84 y1e1 ff2a fs63 fc0 sc0 ls1 ws142">\ufb01gur<span class="_0 blank"></span>ation ren<span class="_0 blank"></span>dered a suc<span class="_0 blank"></span>cessfu<span class="_0 blank"></span>l oral sensi<span class="_0 blank"></span>tizati<span class="_0 blank"></span>on.</div><div class="t m46 x59 h85 y1e2 ff2a fs64 fc10 sc0 ls1">60</div><div class="t m45 xa3 h86 y1e3 ff2d fs65 fc0 sc0 ls1 ws143">PREDICTING<span class="_17 blank"> </span>THE<span class="_17 blank"> </span>ALLERGENIC<span class="_17 blank"> </span>POTENTIAL<span class="_17 blank"> </span>OF</div><div class="t m45 xa3 h86 y1e4 ff2d fs65 fc0 sc0 ls1 ws144">FOOD<span class="_17 blank"> </span>PROTEINS<span class="_17 blank"> </span>BY<span class="_17 blank"> </span>USING<span class="_17 blank"> </span>DIGESTION<span class="_17 blank"> </span>ASSAYS</div><div class="t m45 xa7 h84 y1e5 ff2a fs63 fc0 sc0 ls1 ws142">Based on current knowledge on the relation of<span class="_f blank"> </span>gastrointestinal</div><div class="t m45 xa3 h84 y1e6 ff2a fs63 fc0 sc0 ls1 ws145">digestion, food allergy<span class="_3 blank"></span>, and dietary allergens, digestion experi-</div><div class="t m45 xa3 h84 y1e7 ff2a fs63 fc0 sc0 ls1 ws146">ments have been introduced for assessing the aller<span class="_0 blank"></span>genic capacity</div><div class="t m45 xa3 h84 y1e8 ff2a fs63 fc0 sc0 ls1 ws128">of novel food proteins. In 1996, Astwood et al</div><div class="t m46 xbb h85 y1e9 ff2a fs64 fc10 sc0 ls1">62</div><div class="t m45 xbc h84 y1ea ff2a fs63 fc0 sc0 ls1 ws147">reported in a cut-</div><div class="t m45 xa3 h84 y1eb ff2a fs63 fc0 sc0 ls1 ws148">ting-edge study that digestion experiments in simulated gastric</div><div class="t m45 xa3 h84 y1ec ff2a fs63 fc0 sc0 ls1 ws149">\ufb02uid (SGF) ideally distinguish between potentially<span class="_e blank"> </span>allergenic</div><div class="t m45 xa3 h84 y1ed ff2a fs63 fc0 sc0 ls1 ws14a">and nonallergenic food proteins. Their work was triggered by</div><div class="t m45 xa3 h84 y1ee ff2a fs63 fc0 sc0 ls1 ws14b">reports on<span class="_a blank"> </span>common characteristics<span class="_a blank"> </span>of food allergens</div><div class="t m46 x56 h85 y1ef ff2a fs64 fc10 sc0 ls1">63</div><div class="t m45 x68 h84 y1f0 ff2a fs63 fc0 sc0 ls1 ws14c">and the</div><div class="t m45 xa3 h84 y1f1 ff2a fs63 fc0 sc0 ls1 ws14d">emerging need to predict the allergenic potential of novel dietary</div><div class="t m45 xa3 h84 y1f2 ff2a fs63 fc0 sc0 ls1 ws14e">compounds. The growing number of genetically modi\ufb01ed plants</div><div class="t m45 xa3 h84 y1f3 ff2a fs63 fc0 sc0 ls1 ws14f">entering the market was a challenge for regulatory authorities</div><div class="t m45 xa3 h84 y1f4 ff2a fs63 fc0 sc0 ls1 ws150">to ensure consumer safety<span class="_3 blank"></span>,</div><div class="t m46 x46 h85 y1f5 ff2a fs64 fc10 sc0 ls1">64</div><div class="t m45 xbd h84 y1f6 ff2a fs63 fc0 sc0 ls1 ws151">as indeed potent allergens had pre<span class="_0 blank"></span>vi-</div><div class="t m45 xa3 h84 y1f7 ff2a fs63 fc0 sc0 ls1 ws152">ously been transferred into transgenic food.</div><div class="t m46 x20 h85 y1f8 ff2a fs64 fc10 sc0 ls1">65</div><div class="t m45 x39 h84 y1f9 ff2a fs63 fc0 sc0 ls1 ws13b">Therefore the meth-</div><div class="t m45 xa3 h84 y1fa ff2a fs63 fc0 sc0 ls1 ws153">odology of testing food for its resistance to pepsin digestion was</div><div class="t m45 xa3 h84 y1fb ff2a fs63 fc0 sc0 ls1 ws154">incorporated in a decision tree protocol that was elaborated in a</div><div class="t m45 xa3 h84 y1fc ff2a fs63 fc0 sc0 ls1 ws155">joint Food and Agriculture Organization/W<span class="_3 blank"></span>orld Health Or<span class="_0 blank"></span>ganiza-</div><div class="t m45 xa3 h84 y1fd ff2a fs63 fc0 sc0 ls1 ws151">tion expert meeting in 2001, which was<span class="_10 blank"> </span>approved by the US Food</div><div class="t m45 xa3 h84 y1fe ff2a fs63 fc0 sc0 ls1 ws156">and Drug Administration in 2004.</div><div class="t m46 xf h85 y1ff ff2a fs64 fc10 sc0 ls1">66,67</div><div class="t m45 xbe h84 y200 ff2a fs63 fc0 sc0 ls1 ws157">T<span class="_3 blank"></span>esting proteins for resis-</div><div class="t m45 xa3 h84 y201 ff2a fs63 fc0 sc0 ls1 ws158">tance to SGF exposure has since become a tool extensi<span class="_0 blank"></span>vely</div><div class="t m45 xa3 h84 y202 ff2a fs63 fc0 sc0 ls1 ws159">applied in food allergy research to gain novel insights into food</div><div class="t m45 xa3 h84 y203 ff2a fs63 fc0 sc0 ls1 ws15a">allergen biology<span class="_3 blank"></span>. Peanut allergens were<span class="_18 blank"> </span>discovered to contain</div><div class="t m45 xa3 h84 y204 ff2a fs63 fc0 sc0 ls1 ws15b">large, digestion-stable, allergenic fragments</div><div class="t m46 x25 h85 y205 ff2a fs64 fc10 sc0 ls1">58</div><div class="t m45 x72 h84 y206 ff2a fs63 fc0 sc0 ls1 ws15c">or to form aggre-</div><div class="t m45 xa3 h84 y207 ff2a fs63 fc0 sc0 ls1 ws15d">gates that act as potent triggers of<span class="_f blank"> </span>allergic reactions.</div><div class="t m46 x57 h85 y208 ff2a fs64 fc10 sc0 ls1">68</div><div class="t m45 xbf h84 y209 ff2a fs63 fc0 sc0 ls1 ws13e">Moreover<span class="_3 blank"></span>,</div><div class="t m45 x61 h84 y20a ff2a fs63 fc0 sc0 ls1 ws15e">a multiphase model of gastrointestinal<span class="_19 blank"> </span>digestion has<span class="_19 blank"> </span>been</div><div class="t m45 x61 h84 y20b ff2a fs63 fc0 sc0 ls1 ws15f">developed to analyze emulsi\ufb01cation ef<span class="_0 blank"></span>fects and the effect of</div><div class="t m45 x61 h84 y20c ff2a fs63 fc0 sc0 ls1 ws160">food phospholipid content on dietary protein<span class="_9 blank"> </span>digestibility<span class="_3 blank"></span>.</div><div class="t m46 xc0 h85 y20d ff2a fs64 fc10 sc0 ls1">69,70</div><div class="t m45 x38 h84 y20e ff2a fs63 fc0 sc0 ls1 ws161">It has become evident that some potent allergens are not stable</div><div class="t m45 x61 h84 y20f ff2a fs63 fc0 sc0 ls1 ws162">in SGF<span class="_3 blank"></span>, as previously expected.</div><div class="t m46 x7c h85 y210 ff2a fs64 fc10 sc0 ls1">71-73</div><div class="t m45 xc1 h84 y211 ff2a fs63 fc0 sc0 ls1 ws163">Even though the outcome of</div><div class="t m45 x61 h84 y212 ff2a fs63 fc0 sc0 ls1 ws164">these digestion assays might depend on the applied protein to pep-</div><div class="t m45 x61 h84 y213 ff2a fs63 fc0 sc0 ls1 ws165">sin ratio,</div><div class="t m46 xc2 h85 y1cd ff2a fs64 fc10 sc0 ls1">74</div><div class="t m45 x2e h84 y1ce ff2a fs63 fc0 sc0 ls1 ws166">digestion experiments with the basal gastric pepsin</div><div class="t m45 x61 h84 y1cf ff2a fs63 fc0 sc0 ls1 ws167">concentration for SGF or ev<span class="_0 blank"></span>en pharmaceutical enzyme tablets</div><div class="t m45 x61 h84 y1d0 ff2a fs63 fc0 sc0 ls1 ws168">revealed the quick digestibility of potent allergens, such<span class="_2e blank"> </span>as</div><div class="t m45 x61 h84 y214 ff2a fs63 fc0 sc0 ls1 ws169">milk, \ufb01sh, and hazelnut,<span class="_17 blank"> </span>by gastric<span class="_17 blank"> </span>enzymes.</div><div class="t m46 xc3 h85 y215 ff2a fs64 fc10 sc0 ls1">27,75-79</div><div class="t m45 xc4 h84 y216 ff2a fs63 fc0 sc0 ls1 ws16a">Thus these</div><div class="t m45 x61 h84 y217 ff2a fs63 fc0 sc0 ls1 ws16b">allergens do not sho<span class="_0 blank"></span>w features previously postulated for true class</div><div class="t m45 x61 h84 y218 ff2a fs63 fc0 sc0 ls1 ws16c">1 allergens; howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>,<span class="_9 blank"> </span>they might still<span class="_9 blank"> </span>contain peptide fragments</div><div class="t m45 x61 h84 y219 ff2a fs63 fc0 sc0 ls1 ws16d">recognizable by allergen-speci\ufb01c T cells.</div><div class="t m46 xc5 h85 y1d7 ff2a fs64 fc10 sc0 ls1">80</div><div class="t m45 x61 h86 y21a ff2d fs65 fc0 sc0 ls1 ws16e">PHYSIOLOGICALLY<span class="_17 blank"> </span>AND<span class="_17 blank"> </span>PATHOLOGICALLY</div><div class="t m45 x61 h86 y21b ff2d fs65 fc0 sc0 ls1 ws16f">ALTERED<span class="_17 blank"> </span>GASTRIC<span class="_17 blank"> </span>DIGESTION<span class="_17 blank"> </span>CAPACITY</div><div class="t m45 x38 h84 y21c ff2a fs63 fc0 sc0 ls1 ws170">Interestingly<span class="_3 blank"></span>, gastric digestion<span class="_9 blank"> </span>assays only simulate situations</div><div class="t m45 x61 h84 y21d ff2a fs63 fc0 sc0 ls1 ws171">in which both the production of digestive<span class="_10 blank"> </span>enzymes and the acid-</div><div class="t m45 x61 h84 y21e ff2a fs63 fc0 sc0 ls1 ws172">secretion capacity of the stomach are intact. It is<span class="_f blank"> </span>noteworthy that</div><div class="t m45 x61 h84 y21f ff2a fs63 fc0 sc0 ls1 ws173">the secretory capacity of the stomach changes physiologically</div><div class="t m45 x61 h84 y220 ff2a fs63 fc0 sc0 ls1 ws174">throughout a lifetime, in\ufb02uencing gastric protein digestion. Early</div><div class="t m45 x61 h84 y221 ff2a fs63 fc0 sc0 ls1 ws175">studies indicated that in newborns the intragastric pH ranges from</div><div class="t m45 x61 h84 y222 ff2a fs63 fc0 sc0 ls1 ws176">6.0 to 8.0,</div><div class="t m46 x17 h85 y223 ff2a fs64 fc10 sc0 ls1">81,82</div><div class="t m45 xc6 h84 y1e5 ff2a fs63 fc0 sc0 ls1 ws177">which is followed by a<span class="_10 blank"> </span>burst of acid secretion<span class="_10 blank"> </span>lead-</div><div class="t m45 x61 h84 y1e6 ff2a fs63 fc0 sc0 ls1 ws178">ing to adult gastric pH leve<span class="_0 blank"></span>ls (pH 1.0-3.0) 24 to 48 hours after</div><div class="t m45 x61 h84 y1e7 ff2a fs63 fc0 sc0 ls1 ws179">birth. After these \ufb01rst days of<span class="_10 blank"> </span>life, the gastric acid production re-</div><div class="t m45 x61 h84 y1e8 ff2a fs63 fc0 sc0 ls1 ws17a">mains low during the ne<span class="_0 blank"></span>xt months, and adult pH lev<span class="_0 blank"></span>els in the</div><div class="t m45 x61 h84 y224 ff2a fs63 fc0 sc0 ls1 ws17b">stomach are not reached until the average age of 2<span class="_f blank"> </span>years.</div><div class="t m46 xc0 h85 y225 ff2a fs64 fc10 sc0 ls1">83-87</div><div class="t m45 xc7 h84 y226 ff2a fs63 fc0 sc0 ls1">It</div><div class="t m45 x61 h84 y227 ff2a fs63 fc0 sc0 ls1 ws17c">is well established that gastric acid secretion decreases with</div><div class="t m45 x61 h84 y228 ff2a fs63 fc0 sc0 ls1 ws17d">age, resulting in low gastric acidity in more than 50% of all</div><div class="t m45 x61 h84 y229 ff2a fs63 fc0 sc0 ls1 ws17e">patients aged 60 years and older<span class="_3 blank"></span>.</div><div class="t m46 x1c h85 y1ef ff2a fs64 fc10 sc0 ls1">88</div><div class="t m45 xc8 h84 y1f0 ff2a fs63 fc0 sc0 ls1 ws17f">It has been reported that low</div><div class="t m45 x61 h84 y1f1 ff2a fs63 fc0 sc0 ls1 ws180">gastric acid output is associated with pathologies like atrophic</div><div class="t m45 x61 h84 y1f2 ff2a fs63 fc0 sc0 ls1 ws181">gastritis, celiac disease, diabetes mellitus, rheumatoid arthritis,</div><div class="t m45 x61 h84 y1f3 ff2a fs63 fc0 sc0 ls1 ws182">and Sjo</div><div class="t m45 x5d h87 y22a ff2a fs63 fc0 sc0 ls9d">¨<span class="ls1 ws183 v7">gren syndrome.</span></div><div class="t m46 xc9 h85 y22b ff2a fs64 fc10 sc0 ls1">89-91</div><div class="t m45 x38 h84 y1f6 ff2a fs63 fc0 sc0 ls1 ws184">On the other hand,<span class="_f blank"> </span>increase of the gastric pH<span class="_f blank"> </span>is the therapeutic</div><div class="t m45 x61 h84 y1f7 ff2a fs63 fc0 sc0 ls1 ws185">goal in patients with dyspepsia, such as<span class="_9 blank"> </span>gastritis, ulcer<span class="_0 blank"></span>, erosions,</div><div class="t m45 x61 h84 y22c ff2a fs63 fc0 sc0 ls1 ws186">and re\ufb02ux symptoms. Approximately 25% to 54% of the adult</div><div class="t m45 x61 h84 y22d ff2a fs63 fc0 sc0 ls1 ws187">population in W<span class="_3 blank"></span>estern countries is affected by dyspeptic disorders</div><div class="t m45 x61 h84 y22e ff2a fs63 fc0 sc0 ls1 ws188">per year<span class="_3 blank"></span>.</div><div class="t m46 x5b h85 y22f ff2a fs64 fc10 sc0 ls1">92-95</div><div class="t m45 x3b h84 y230 ff2a fs63 fc0 sc0 ls1 ws189">Even though most of them<span class="_f blank"> </span>take medication without</div><div class="t m45 x61 h84 y231 ff2a fs63 fc0 sc0 ls1 ws18a">specialist consultation and adequate diagnosis, dyspeptic symp-</div><div class="t m45 x61 h84 y232 ff2a fs63 fc0 sc0 ls1 ws18b">toms account for up to 5% of<span class="_9 blank"> </span>all consultations to general practi-</div><div class="t m45 x61 h84 y233 ff2a fs63 fc0 sc0 ls1">tioners.</div><div class="t m46 x4b h85 y234 ff2a fs64 fc10 sc0 ls1">96-98</div><div class="t m45 x6b h84 y235 ff2a fs63 fc0 sc0 ls1 ws18c">Moreover<span class="_3 blank"></span>, gastroesophageal<span class="_9 blank"> </span>re\ufb02ux (ie, the presence</div><div class="t m45 x61 h84 y236 ff2a fs63 fc0 sc0 ls1 ws18d">of gastric \ufb02uid proximal to the stomach) is one of the most prev-</div><div class="t m45 x61 h84 y237 ff2a fs63 fc0 sc0 ls1 ws18e">alent problems affecting the gastrointestinal tract in infanc<span class="_0 blank"></span>y<span class="_3 blank"></span>,</div><div class="t m46 xca h85 y238 ff2a fs64 fc10 sc0 ls1">99</div><div class="t m45 xcb h84 y239 ff2a fs63 fc0 sc0 ls1">be-</div><div class="t m45 x61 h84 y23a ff2a fs63 fc0 sc0 ls1 ws18f">ing today treated with long-term acid suppression by<span class="_10 blank"> </span>proton pump</div><div class="t m45 x61 h84 y23b ff2a fs63 fc0 sc0 ls1 ws190">inhibitors (PPIs) or H2-receptor blockers.</div><div class="t m46 xcc h85 y208 ff2a fs64 fc10 sc0 ls1">100-102</div><div class="t m45 xcd h88 y23c ff2d fs66 fc0 sc0 ls1 ws191">FIG 1.<span class="_17 blank"> </span><span class="ff2e ws192">Physiologic<span class="_8 blank"> </span>gastric<span class="_8 blank"> </span>protein<span class="_8 blank"> </span>digestion<span class="_8 blank"> </span>by<span class="_8 blank"> </span>pepsin.<span class="_8 blank"> </span>After<span class="_8 blank"> </span>activation<span class="_8 blank"> </span>of<span class="_8 blank"> </span>pepsin,<span class="_8 blank"> </span>the<span class="_8 blank"> </span>substrate-binding<span class="_8 blank"> </span>cleft</span></div><div class="t m45 xcd h88 y23d ff2e fs66 fc0 sc0 ls1 ws193">is accessible for proteins, and protein cleavage into peptides takes place. The \ufb01gure was created with the</div><div class="t m45 xcd h88 y23e ff2e fs66 fc0 sc0 ls1 ws194">program Protein Explorer 2.411 Beta (available at:<span class="_10 blank"> </span><span class="fc10 ws195">http://proteinexplorer.org</span><span class="ws196">)<span class="_10 blank"> </span>by<span class="_10 blank"> </span>using<span class="_10 blank"> </span>the<span class="_10 blank"> </span>structural<span class="_10 blank"> </span>infor-</span></div><div class="t m45 xcd h88 y23f ff2e fs66 fc0 sc0 ls1 ws197">mation<span class="_f blank"> </span>of<span class="_f blank"> </span>porcine<span class="_f blank"> </span>pepsin<span class="_f blank"> </span>provided<span class="_f blank"> </span>with<span class="_f blank"> </span>the<span class="_f blank"> </span>Research<span class="_f blank"> </span>Collaboratory<span class="_f blank"> </span>for<span class="_f blank"> </span>Structural<span class="_f blank"> </span>Bioinformatics<span class="_f blank"> </span>Protein</div><div class="t m45 xcd h88 y240 ff2e fs66 fc0 sc0 ls1 ws198">Data<span class="_10 blank"> </span>Bank<span class="_10 blank"> </span>accession<span class="_10 blank"> </span>number<span class="_10 blank"> </span>5PEP.</div><div class="t m45 xa3 h89 y241 ff2e fs67 fc0 sc0 ls1 ws199">J ALLERGY CLIN IMMUNOL</div><div class="t m45 xa3 h89 y242 ff2e fs67 fc0 sc0 ls1 ws19a">VOLUME 121, NUMBER 6</div><div class="t m45 xce h8a y241 ff2e fs68 fc0 sc0 ls1 ws19b">UNTERSMAYR AND JENSEN-JAROLIM<span class="_a blank"> </span><span class="ff2d">1303</span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 xcf h2f y243 ff4 fs4 fc0 sc0 ls1 wsb">Digestão Proteica gástrica pela </div><div class="t m1 x34 h2f y244 ff4 fs4 fc0 sc0 ls28 ws19c">Pepsina</div></div><div class="c x3 yc w2 h4"><div class="t m1 x27 h10 yd2 ff2 fsc fc3 sc0 ls1e wse0">Untersmayr <span class="ls1f wsb">E, <span class="ls72 wse1">Jensen<span class="ls1 ws2e">-</span><span class="wse2">Jarolim </span></span>E. <span class="ls72 wsdc">Journa<span class="_0 blank"></span>l <span class="ls22 wsdd">of <span class="ls21 wse3">Allergy <span class="ls25 ws20">and <span class="ls1e wsda">Clinical <span class="ls26 wsb">Immunology. 2008 Jun;121(6):1301<span class="ls1 ws2e">\u2013</span><span class="ls25">8. </span></span></span></span></span></span></span></span></div></div><div class="c x34 y245 w7 h7b"><div class="t m43 x80 h7c y188 ff26 fs5d fc0 sc0 ls1 wse4">time points of <span class="ff27 wse5">in vitr<span class="_3 blank"></span>o<span class="_a blank"> </span><span class="ff26 wse6">digestion in a patie<span class="_0 blank"></span>nt with gras<span class="_0 blank"></span>s pollen</span></span></div><div class="t m43 x81 h7c y189 ff26 fs5d fc0 sc0 ls1 wse7">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_0 blank"></span>wed th<span class="_0 blank"></span>at gastri<span class="_0 blank"></span>c dige<span class="_0 blank"></span>stion sub<span class="_0 blank"></span>stan<span class="_0 blank"></span>tially</div><div class="t m43 x82 h7c y18a ff26 fs5d fc0 sc0 ls1 wse8">decreas<span class="_0 blank"></span>ed the aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>nic capacity of the<span class="_0 blank"></span>se cross<span class="_0 blank"></span>-reacti<span class="_3 blank"></span>ve food</div><div class="t m43 x83 h7c y18b ff26 fs5d fc0 sc0 ls1 wse9">protein<span class="_0 blank"></span>s (<span class="fc10 wsea">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n testin<span class="_0 blank"></span>g in<span class="_a blank"> </span>pat<span class="_0 blank"></span>ients wit<span class="_0 blank"></span>h \ufb01<span class="_0 blank"></span>sh all<span class="_0 blank"></span>ergy<span class="_a blank"> </span>wit<span class="_0 blank"></span>h</span></span></div><div class="t m43 x84 h7c y18c ff26 fs5d fc0 sc0 ls1 wseb">SGF-p<span class="_0 blank"></span>redige<span class="_0 blank"></span>sted or SGF-u<span class="_0 blank"></span>ndi<span class="_0 blank"></span>gested co<span class="_0 blank"></span>d\ufb01sh all<span class="_0 blank"></span>erge<span class="_0 blank"></span>ns sho<span class="_3 blank"></span>wed a</div><div class="t m43 x85 h7c y18d ff26 fs5d fc0 sc0 ls1 wsec">signi\ufb01<span class="_0 blank"></span>can<span class="_0 blank"></span>t diges<span class="_0 blank"></span>tion tim<span class="_0 blank"></span>e-d<span class="_0 blank"></span>epende<span class="_0 blank"></span>nt redu<span class="_0 blank"></span>cti<span class="_0 blank"></span>on of<span class="_9 blank"> </span>induce<span class="_0 blank"></span>d wheal</div><div class="t m43 x86 h7c y18e ff26 fs5d fc0 sc0 ls1 wsed">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>v<span class="_0 blank"></span>er<span class="_0 blank"></span>, double<span class="_0 blank"></span>-blin<span class="_0 blank"></span>d, place<span class="_0 blank"></span>bo-co<span class="_0 blank"></span>ntroll<span class="_0 blank"></span>ed, food</div><div class="t m43 x87 h7c y18f ff26 fs5d fc0 sc0 ls1 wsee">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tients wit<span class="_0 blank"></span>h \ufb01sh all<span class="_0 blank"></span>ergy<span class="_9 blank"> </span>res<span class="_0 blank"></span>ulted in a 10- to</div><div class="t m43 x88 h7c y190 ff26 fs5d fc0 sc0 ls1 wsef">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ated all<span class="_0 blank"></span>ergen dos<span class="_0 blank"></span>e if the \ufb01sh prot<span class="_0 blank"></span>eins were pre-</div><div class="t m43 x89 h7c y191 ff26 fs5d fc0 sc0 ls1 wsf0">viousl<span class="_0 blank"></span>y subjected to <span class="ff27 wsf1">in vit<span class="_0 blank"></span>r<span class="_3 blank"></span>o<span class="_f blank"> </span><span class="ff26 wsf2">gastric dige<span class="_0 blank"></span>stion.</span></span></div><div class="t m44 x8a h7d y192 ff26 fs5e fc10 sc0 ls1">27</div><div class="t m43 x8b h7e y193 ff28 fs5f fc0 sc0 ls1 wsf3">SAFETY<span class="_a blank"> </span>ISSUES<span class="_17 blank"> </span>AND<span class="_a blank"> </span>CLINICAL<span class="_17 blank"> </span>IMPLICATIONS</div><div class="t m43 x8c h7e y194 ff28 fs5f fc0 sc0 ls1 wsf4">FOR<span class="_17 blank"> </span>ALLERG IC<span class="_a blank"> </span>AND<span class="_17 blank"> </span>NONALLER GIC<span class="_a blank"> </span>CONSUMERS</div><div class="t m43 x8d h7c y195 ff26 fs5d fc0 sc0 ls1 wsf5">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m43 x8e h7c y196 ff26 fs5d fc0 sc0 ls1 wsf6">clinical outcome after the consumption of<span class="_a blank"> </span>a digestion-sensitiv<span class="_0 blank"></span>e</div><div class="t m43 x8f h7c y197 ff26 fs5d fc0 sc0 ls1 wsf7">dietary protein depends to a certain<span class="_10 blank"> </span>degree on the gastric digestiv<span class="_0 blank"></span>e</div><div class="t m43 x90 h7c y198 ff26 fs5d fc0 sc0 ls1 wsf8">capacity<span class="_3 blank"></span>. If the food protein is<span class="_f blank"> </span>exposed to gastric enzymes during</div><div class="t m43 x8d h7c y199 ff26 fs5d fc0 sc0 ls1 wsf9">transit, protein cleavage takes place, inducing either oral toler-</div><div class="t m43 x91 h7c y19a ff26 fs5d fc0 sc0 ls1 wsfa">ance or immune ignorance toward the ingested food protein.</div><div class="t m43 x92 h7c y19b ff26 fs5d fc0 sc0 ls1 wsfb">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m43 x93 h7c y19c ff26 fs5d fc0 sc0 ls1 wsfc">impaired digestion, such as during acid-suppression treatment,</div><div class="t m43 x94 h7c y19d ff26 fs5d fc0 sc0 ls1 wsfd">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m43 x95 h7c y19e ff26 fs5d fc0 sc0 ls1 wsfe">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m43 x96 h7c y19f ff26 fs5d fc0 sc0 ls1 wsff">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m43 x97 h7c y1a0 ff26 fs5d fc0 sc0 ls1 ws100">the allergenic capacity<span class="_9 blank"> </span>of ingested food<span class="_9 blank"> </span>proteins, whereas severe</div><div class="t m43 x98 h7c y1a1 ff26 fs5d fc0 sc0 ls1 ws101">allergic reactions at much lower amounts of ingested food</div><div class="t m43 x99 h7c y1a2 ff26 fs5d fc0 sc0 ls1 ws102">proteins could occur if digestion is impaired (<span class="_1 blank"> </span><span class="fc10 ws103">Fig 3</span>).</div><div class="t m43 x9a h7c y1a3 ff26 fs5d fc0 sc0 ls1 ws104">The revie<span class="_0 blank"></span>wed data<span class="_a blank"> </span>indicate<span class="_a blank"> </span>that<span class="_18 blank"> </span>the current<span class="_a blank"> </span>concept<span class="_a blank"> </span>of food</div><div class="t m43 x9b h7c y1a4 ff26 fs5d fc0 sc0 ls1 ws105">allergen classi\ufb01cation into class 1<span class="_f blank"> </span>(true food allergen) and<span class="_f blank"> </span>class 2</div><div class="t m43 x9c h7c y1a5 ff26 fs5d fc0 sc0 ls1 ws106">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m43 x9d h7c y1a6 ff26 fs5d fc0 sc0 ls1 ws107">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m43 x9a h7c y1a7 ff26 fs5d fc0 sc0 ls1 ws108">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m43 x4a h7c y1a8 ff26 fs5d fc0 sc0 ls1 ws109">and<span class="_10 blank"> </span>consumers\u2019 safety<span class="_f blank"> </span>might<span class="_10 blank"> </span>be<span class="_f blank"> </span>en<span class="_0 blank"></span>visaged<span class="_10 blank"> </span>(<span class="fc10 ws10a">T<span class="_3 blank"></span>able II<span class="fc0 ws10b">). It should be</span></span></div><div class="t m43 x9e h7f y1a9 ff28 fs60 fc0 sc0 ls1 ws10c">FIG 3.<span class="_a blank"> </span><span class="ff29 ws10d">The gate-keeping function of the stomach in the sensitization and</span></div><div class="t m43 x9f h7f y1aa ff29 fs60 fc0 sc0 ls1 ws10e">effector phase of food allergy. The fate of a dietary protein<span class="_10 blank"> </span>depends<span class="_f blank"> </span>on the</div><div class="t m43 xa0 h7f y1ab ff29 fs60 fc0 sc0 ls1 ws10f">gastric<span class="_a blank"> </span>digestive<span class="_a blank"> </span>function<span class="_17 blank"> </span>mainly<span class="_a blank"> </span>accomplished<span class="_a blank"> </span>by<span class="_a blank"> </span>the<span class="_17 blank"> </span>gastric<span class="_a blank"> </span>protease</div><div class="t m43 xa1 h7f y1ac ff29 fs60 fc0 sc0 ls1 ws110">pepsin. If the protein<span class="_17 blank"> </span>structure is destroyed beca<span class="_1 blank"> </span>use of proteolysis, oral</div><div class="t m43 xa2 h7f y1ad ff29 fs60 fc0 sc0 ls1 ws111">tolerance<span class="_8 blank"> </span>or<span class="_8 blank"> </span>immune<span class="_8 blank"> </span>ignorance<span class="_8 blank"> </span>and<span class="_8 blank"> </span>a<span class="_8 blank"> </span>reduce d<span class="_8 blank"> </span>allerge nic<span class="_10 blank"> </span>potential<span class="_6 blank"> </span>might<span class="_8 blank"> </span>be</div><div class="t m43 xa3 h7f y1ae ff29 fs60 fc0 sc0 ls1 ws112">the<span class="_2e blank"> </span>result.<span class="_22 blank"> </span>However,<span class="_22 blank"> </span>when<span class="_2e blank"> </span>gastric<span class="_22 blank"> </span>digestion<span class="_22 blank"> </span>is<span class="_2e blank"> </span>imp aired<span class="_22 blank"> </span>(eg,<span class="_22 blank"> </span>under</div><div class="t m43 xa4 h7f y1af ff29 fs60 fc0 sc0 ls1 ws113">hypoacidic<span class="_f blank"> </span>gastric<span class="_f blank"> </span>conditions),<span class="_f blank"> </span>digestion-labile<span class="_f blank"> </span>proteins<span class="_f blank"> </span>might<span class="_f blank"> </span>trigger<span class="_f blank"> </span>oral</div><div class="t m43 xa5 h7f y1b0 ff29 fs60 fc0 sc0 ls1 ws114">sensitization or severe allergic symptoms<span class="_9 blank"> </span>in a previousl<span class="_1 blank"> </span>y sensitized indi-</div><div class="t m43 xa6 h7f y1b1 ff29 fs60 fc0 sc0 ls1 ws115">vidual.<span class="_17 blank"> </span>The<span class="_17 blank"> </span>\ufb01gure<span class="_17 blank"> </span>was<span class="_17 blank"> </span>created<span class="_a blank"> </span>with<span class="_17 blank"> </span>the<span class="_17 blank"> </span>structural<span class="_17 blank"> </span>information<span class="_17 blank"> </span>provided</div><div class="t m43 xa7 h7f y1b2 ff29 fs60 fc0 sc0 ls1 ws116">from<span class="_a blank"> </span>Research<span class="_a blank"> </span>Collaboratory<span class="_a blank"> </span>for<span class="_a blank"> </span>Structural<span class="_a blank"> </span>Bioinformatics<span class="_a blank"> </span>Protein<span class="_a blank"> </span>Data</div><div class="t m43 xa8 h7f y1b3 ff29 fs60 fc0 sc0 ls1 ws116">Bank<span class="_10 blank"> </span>accession<span class="_f blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_10 blank"> </span>and<span class="_f blank"> </span>5PEP.</div><div class="t m43 xa9 h7f y1b4 ff28 fs60 fc0 sc0 ls1 ws117">FIG<span class="_18 blank"> </span>2. <span class="ff29 ws111">Reduced<span class="_e blank"> </span>allergenicity<span class="_e blank"> </span>of<span class="_18 blank"> </span>melo n<span class="_e blank"> </span>allergens<span class="_e blank"> </span>after<span class="_18 blank"> </span>incubation<span class="_e blank"> </span>with</span></div><div class="t m43 xaa h7f y1b5 ff29 fs60 fc0 sc0 ls1 ws118">gastric enzymes. After subjection to<span class="_10 blank"> </span>SGF, melon allergens induc<span class="_1 blank"> </span>e a smaller</div><div class="t m43 xab h7f y1b6 ff29 fs60 fc0 sc0 ls1 ws119">wheal reaction in a patient with melon<span class="_17 blank"> </span>allergy compared with the undi-</div><div class="t m43 xac h7f y1b7 ff29 fs60 fc0 sc0 ls1 ws11a">gested<span class="_a blank"> </span>extract.<span class="_18 blank"> </span>The<span class="_a blank"> </span>alteration<span class="_a blank"> </span>of<span class="_18 blank"> </span>skin<span class="_a blank"> </span>reactivity<span class="_a blank"> </span>was<span class="_a blank"> </span>dependen t<span class="_18 blank"> </span>on<span class="_a blank"> </span>the</div><div class="t m43 xad h7f y1b8 ff29 fs60 fc0 sc0 ls1 ws11b">incubation<span class="_f blank"> </span>time<span class="_10 blank"> </span>with<span class="_f blank"> </span>the<span class="_10 blank"> </span>proteolytic<span class="_f blank"> </span>enzymes.</div><div class="t m43 xae h80 y1b9 ff28 fs61 fc0 sc0 ls1 ws11c">TABLE II. <span class="ff29 ws11d">Key concepts and<span class="_9 blank"> </span>safety implications</span></div><div class="t m43 xaf h81 y1ba ff26 fs61 fc0 sc0 ls1 ws11e">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m43 xb0 h81 y1bb ff26 fs61 fc0 sc0 ls1 ws11f">safety tests for novel (eg, genetically modi\ufb01ed) food compounds.</div><div class="t m43 xb1 h81 y1bc ff26 fs61 fc0 sc0 ls1 ws120">Patients should be advised that<span class="_9 blank"> </span>threshold levels might vary in situations of</div><div class="t m43 xb2 h81 y1bd ff26 fs61 fc0 sc0 ls1 ws121">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current efforts to</div><div class="t m43 xb3 h81 y1be ff26 fs61 fc0 sc0 ls1 ws122">de\ufb01ne no-observed-adv<span class="_0 blank"></span>erse-ef<span class="_0 blank"></span>fect lev<span class="_0 blank"></span>els for food allergens.</div><div class="t m43 xb4 h81 y1bf ff26 fs61 fc0 sc0 ls1 ws123">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m43 xb5 h81 y1c0 ff26 fs61 fc0 sc0 ls1 ws122">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m43 xb6 h81 y1c1 ff26 fs61 fc0 sc0 ls1 ws124">food ingestion.</div><div class="t m43 xb7 h82 y1c2 ff29 fs62 fc0 sc0 ls1 ws125">J ALLERGY CLIN IMMUNOL</div><div class="t m43 xb8 h82 y1c3 ff29 fs62 fc0 sc0 ls1 ws126">VOLUME 121, NUMBER 6</div><div class="t m43 x9f h80 y1c4 ff29 fs61 fc0 sc0 ls1 ws127">UNTERSMAYR AND JENSEN-JAROLIM<span class="_a blank"> </span><span class="ff28">1305</span></div></div><div class="c xd0 y246 w9 h8b"><div class="t m47 xd1 h8c y247 ff2f fs69 fc0 sc0 ls1 ws19d">time points of <span class="ff30 ws19e">in vitr<span class="_3 blank"></span>o<span class="_a blank"> </span><span class="ff2f ws19f">digestio<span class="_0 blank"></span>n in a patient with<span class="_17 blank"> </span>grass pollen</span></span></div><div class="t m47 xd1 h8c y248 ff2f fs69 fc0 sc0 ls1 ws1a0">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_0 blank"></span>wed that ga<span class="_0 blank"></span>stric dige<span class="_0 blank"></span>sti<span class="_0 blank"></span>on subst<span class="_0 blank"></span>antia<span class="_0 blank"></span>lly</div><div class="t m47 xd1 h8c y249 ff2f fs69 fc0 sc0 ls1 ws1a1">decreas<span class="_0 blank"></span>ed the aller<span class="_0 blank"></span>genic cap<span class="_0 blank"></span>acity of the<span class="_0 blank"></span>se cross-r<span class="_0 blank"></span>eacti<span class="_3 blank"></span>ve food</div><div class="t m47 xd1 h8c y24a ff2f fs69 fc0 sc0 ls1 ws1a2">protein<span class="_0 blank"></span>s (<span class="fc10 ws1a3">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n testin<span class="_0 blank"></span>g in pat<span class="_0 blank"></span>ien<span class="_0 blank"></span>ts with \ufb01<span class="_0 blank"></span>sh all<span class="_0 blank"></span>ergy<span class="_17 blank"> </span>with</span></span></div><div class="t m47 xd1 h8c y24b ff2f fs69 fc0 sc0 ls1 ws1a4">SGF-pre<span class="_0 blank"></span>dige<span class="_0 blank"></span>sted or SGF-u<span class="_0 blank"></span>ndiges<span class="_0 blank"></span>ted cod\ufb01<span class="_0 blank"></span>sh aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>ns sho<span class="_0 blank"></span>wed a</div><div class="t m47 xd1 h8c y24c ff2f fs69 fc0 sc0 ls1 ws1a5">signi\ufb01<span class="_0 blank"></span>can<span class="_0 blank"></span>t diges<span class="_0 blank"></span>tion tim<span class="_0 blank"></span>e-depe<span class="_0 blank"></span>ndent<span class="_f blank"> </span>reduction of<span class="_f blank"> </span>induced wheal</div><div class="t m47 xd1 h8c y24d ff2f fs69 fc0 sc0 ls1 ws1a6">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>ver<span class="_3 blank"></span>, double-blin<span class="_0 blank"></span>d, placebo-<span class="_0 blank"></span>contr<span class="_0 blank"></span>oll<span class="_0 blank"></span>ed, food</div><div class="t m47 xd1 h8c y24e ff2f fs69 fc0 sc0 ls1 ws1a7">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tients wit<span class="_0 blank"></span>h \ufb01sh aller<span class="_0 blank"></span>gy res<span class="_0 blank"></span>ulted in a 10- to</div><div class="t m47 xd1 h8c y24f ff2f fs69 fc0 sc0 ls1 ws1a8">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ated all<span class="_0 blank"></span>ergen dos<span class="_0 blank"></span>e if the \ufb01sh protein<span class="_0 blank"></span>s were pre-</div><div class="t m47 xd1 h8c y250 ff2f fs69 fc0 sc0 ls1 ws1a9">viousl<span class="_0 blank"></span>y subjected to <span class="ff30 ws1aa">in vit<span class="_0 blank"></span>r<span class="_3 blank"></span>o<span class="_f blank"> </span><span class="ff2f ws1ab">gastric dige<span class="_0 blank"></span>stion.</span></span></div><div class="t m48 xd2 h8d y251 ff2f fs6a fc10 sc0 ls1">27</div><div class="t m47 xd1 h8e y252 ff31 fs6b fc0 sc0 ls1 ws1ac">SAFETY<span class="_17 blank"> </span>ISSUES<span class="_17 blank"> </span>AND<span class="_17 blank"> </span>CLINICAL<span class="_17 blank"> </span>IMPLICA TIONS</div><div class="t m47 xd1 h8e y253 ff31 fs6b fc0 sc0 ls1 ws1ad">FOR<span class="_17 blank"> </span>ALLERGIC<span class="_17 blank"> </span>AND<span class="_17 blank"> </span>NONALLERGIC<span class="_17 blank"> </span>CONS UMERS</div><div class="t m47 xd3 h8c y254 ff2f fs69 fc0 sc0 ls1 ws1ae">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m47 xd1 h8c y255 ff2f fs69 fc0 sc0 ls1 ws1af">clinical outcome after the consumption of<span class="_17 blank"> </span>a digestion-sensitive</div><div class="t m47 xd1 h8c y256 ff2f fs69 fc0 sc0 ls1 ws1b0">dietary protein depends to a certain degree on the gastric digestive</div><div class="t m47 xd1 h8c y257 ff2f fs69 fc0 sc0 ls1 ws1b1">capacity<span class="_3 blank"></span>. If the food protein is<span class="_f blank"> </span>exposed to gastric enzymes during</div><div class="t m47 xd1 h8c y258 ff2f fs69 fc0 sc0 ls1 ws1b2">transit, protein cleavage takes place, inducing either oral toler-</div><div class="t m47 xd1 h8c y259 ff2f fs69 fc0 sc0 ls1 ws1b3">ance or immune ignorance toward the ingested food protein.</div><div class="t m47 xd1 h8c y25a ff2f fs69 fc0 sc0 ls1 ws1b4">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m47 xd1 h8c y25b ff2f fs69 fc0 sc0 ls1 ws1b5">impaired digestion, such as during acid-suppression treatment,</div><div class="t m47 x9b h8c y25c ff2f fs69 fc0 sc0 ls1 ws1b6">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m47 x9b h8c y25d ff2f fs69 fc0 sc0 ls1 ws1b7">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m47 x9b h8c y25e ff2f fs69 fc0 sc0 ls1 ws1b8">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m47 x9b h8c y25f ff2f fs69 fc0 sc0 ls1 ws1b9">the allergenic capacity<span class="_f blank"> </span>of ingested<span class="_9 blank"> </span>food proteins, whereas severe</div><div class="t m47 x9b h8c y260 ff2f fs69 fc0 sc0 ls1 ws1ba">allergic reactions at much lower amounts of ingested food</div><div class="t m47 x9b h8c y261 ff2f fs69 fc0 sc0 ls1 ws1bb">proteins could occur if digestion is impaired (<span class="fc10 ws1bc">Fig 3</span>).</div><div class="t m47 x4a h8c y262 ff2f fs69 fc0 sc0 ls1 ws1bd">The revie<span class="_0 blank"></span>wed data<span class="_a blank"> </span>indicate that<span class="_a blank"> </span>the current<span class="_a blank"> </span>concept of food</div><div class="t m47 x9b h8c y263 ff2f fs69 fc0 sc0 ls1 ws1be">allergen classi\ufb01cation into class 1 (true<span class="_f blank"> </span>food allergen) and class 2</div><div class="t m47 x9b h8c y264 ff2f fs69 fc0 sc0 ls1 ws1bf">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m47 x9b h8c y265 ff2f fs69 fc0 sc0 ls1 ws1c0">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m47 x9b h8c y266 ff2f fs69 fc0 sc0 ls1 ws1c1">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m47 x9b h8c y267 ff2f fs69 fc0 sc0 ls1 ws1c2">and<span class="_10 blank"> </span>consumers\u2019 safety<span class="_10 blank"> </span>might<span class="_10 blank"> </span>be<span class="_10 blank"> </span>envisaged<span class="_10 blank"> </span>(<span class="fc10 ws1c3">T<span class="_3 blank"></span>able II<span class="fc0 ws1c4">). It should be</span></span></div><div class="t m47 x9b h8f y268 ff31 fs6c fc0 sc0 ls1 ws1c5">FIG 3.<span class="_17 blank"> </span><span class="ff32 ws1c6">The gate-keeping function of the stomach in the sensiti<span class="_1 blank"> </span>zation and</span></div><div class="t m47 x9b h8f y269 ff32 fs6c fc0 sc0 ls1 ws1c7">effector phase of food allergy. The fate of a dietary protein depends<span class="_10 blank"> </span>on the</div><div class="t m47 x9b h8f y26a ff32 fs6c fc0 sc0 ls1 ws1c8">gastric<span class="_17 blank"> </span>digestive<span class="_a blank"> </span>function<span class="_17 blank"> </span>mainly<span class="_17 blank"> </span>accomplished<span class="_a blank"> </span>by<span class="_17 blank"> </span>the<span class="_17 blank"> </span>gastric<span class="_a blank"> </span>protease</div><div class="t m47 x9b h8f y26b ff32 fs6c fc0 sc0 ls1 ws1c9">pepsin. If the protein<span class="_17 blank"> </span>structure is destroyed because of proteolysis,<span class="_17 blank"> </span>oral</div><div class="t m47 x9b h8f y26c ff32 fs6c fc0 sc0 ls1 ws1ca">tolerance<span class="_8 blank"> </span>or<span class="_6 blank"> </span>immune<span class="_8 blank"> </span>ignor ance<span class="_8 blank"> </span>and<span class="_8 blank"> </span>a<span class="_8 blank"> </span>reduced<span class="_8 blank"> </span>allergenic<span class="_8 blank"> </span>potential<span class="_6 blank"> </span>might<span class="_8 blank"> </span>be</div><div class="t m47 x9b h8f y26d ff32 fs6c fc0 sc0 ls1 ws1cb">the<span class="_15 blank"> </span>result.<span class="_2e blank"> </span>However,<span class="_15 blank"> </span>when<span class="_2e blank"> </span>gastric<span class="_15 blank"> </span>digestion<span class="_2e blank"> </span>is<span class="_15 blank"> </span>imp aired<span class="_2e blank"> </span>(eg,<span class="_15 blank"> </span>under</div><div class="t m47 x9b h8f y26e ff32 fs6c fc0 sc0 ls1 ws1cc">hypoacidic<span class="_10 blank"> </span>gastric<span class="_f blank"> </span>conditions),<span class="_f blank"> </span>digestion-labile<span class="_10 blank"> </span>protein<span class="_1 blank"> </span>s<span class="_10 blank"> </span>might<span class="_f blank"> </span>trigger<span class="_f blank"> </span>oral</div><div class="t m47 x9b h8f y26f ff32 fs6c fc0 sc0 ls1 ws1cd">sensitization or severe allergic symptoms<span class="_9 blank"> </span>in a previously sensitized indi-</div><div class="t m47 x9b h8f y270 ff32 fs6c fc0 sc0 ls1 ws1ce">vidual.<span class="_17 blank"> </span>The<span class="_9 blank"> </span>\ufb01gure<span class="_17 blank"> </span>was<span class="_17 blank"> </span>created<span class="_9 blank"> </span>with<span class="_17 blank"> </span>the<span class="_17 blank"> </span>structural<span class="_17 blank"> </span>information<span class="_9 blank"> </span>provided</div><div class="t m47 x9b h8f y271 ff32 fs6c fc0 sc0 ls1 ws1cf">from<span class="_17 blank"> </span>Research<span class="_a blank"> </span>Collaboratory<span class="_a blank"> </span>for<span class="_17 blank"> </span>Structural<span class="_a blank"> </span>Bioinformatics<span class="_17 blank"> </span>Protein<span class="_a blank"> </span>Data</div><div class="t m47 x9b h8f y272 ff32 fs6c fc0 sc0 ls1 ws1cf">Bank<span class="_10 blank"> </span>accession<span class="_10 blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_10 blank"> </span>and<span class="_10 blank"> </span>5PEP.</div><div class="t m47 xd1 h8f y273 ff31 fs6c fc0 sc0 ls1 ws1d0">FIG<span class="_18 blank"> </span>2. <span class="ff32 ws1ca">Reduced<span class="_a blank"> </span>allerge nicity<span class="_18 blank"> </span>of<span class="_18 blank"> </span>melon<span class="_18 blank"> </span>allergens<span class="_18 blank"> </span>after<span class="_18 blank"> </span>incubation<span class="_18 blank"> </span>with</span></div><div class="t m47 xd1 h8f y274 ff32 fs6c fc0 sc0 ls1 ws1d1">gastric enzymes. After subjection to SGF,<span class="_10 blank"> </span>melon allergens induce a smaller</div><div class="t m47 xd1 h8f y275 ff32 fs6c fc0 sc0 ls1 ws1d2">wheal reaction in a patient with melon<span class="_17 blank"> </span>allergy compared with the undi-</div><div class="t m47 xd1 h8f y276 ff32 fs6c fc0 sc0 ls1 ws1d3">gested<span class="_a blank"> </span>extract.<span class="_a blank"> </span>The<span class="_17 blank"> </span>alteration<span class="_a blank"> </span>of<span class="_a blank"> </span>skin<span class="_a blank"> </span>reactivity<span class="_17 blank"> </span>was<span class="_a blank"> </span>dependent<span class="_a blank"> </span>on<span class="_a blank"> </span>the</div><div class="t m47 xd1 h8f y277 ff32 fs6c fc0 sc0 ls1 ws1d4">incubation<span class="_10 blank"> </span>time<span class="_10 blank"> </span>with<span class="_f blank"> </span>the<span class="_10 blank"> </span>proteolytic<span class="_10 blank"> </span>enzymes.</div><div class="t m47 x9b h90 y278 ff31 fs6d fc0 sc0 ls1 ws1d5">TABLE II. <span class="ff32 ws1d6">Key concepts and safety implications</span></div><div class="t m47 x9b h91 y279 ff2f fs6d fc0 sc0 ls1 ws1d7">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m47 x9a h91 y27a ff2f fs6d fc0 sc0 ls1 ws1d8">safety tests for novel (eg, genetically modi\ufb01ed) food compounds.</div><div class="t m47 x9b h91 y27b ff2f fs6d fc0 sc0 ls1 ws1d9">Patients should be advised that<span class="_9 blank"> </span>threshold le<span class="_0 blank"></span>vels might vary in situations of</div><div class="t m47 x9a h91 y27c ff2f fs6d fc0 sc0 ls1 ws1da">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current efforts to</div><div class="t m47 x9a h91 y27d ff2f fs6d fc0 sc0 ls1 ws1db">de\ufb01ne no-observed-adv<span class="_0 blank"></span>erse-ef<span class="_0 blank"></span>fect lev<span class="_0 blank"></span>els for food allergens.</div><div class="t m47 x9b h91 y27e ff2f fs6d fc0 sc0 ls1 ws1dc">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m47 x9a h91 y27f ff2f fs6d fc0 sc0 ls1 ws1db">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m47 x9a h91 y280 ff2f fs6d fc0 sc0 ls1 ws1dd">food ingestion.</div><div class="t m47 xd1 h92 y281 ff32 fs6e fc0 sc0 ls1 ws1de">J ALLERGY CLIN IMMUNOL</div><div class="t m47 xd1 h92 y282 ff32 fs6e fc0 sc0 ls1 ws1df">VOLUME 121, NUMBER 6</div><div class="t m47 x2c h90 y281 ff32 fs6d fc0 sc0 ls1 ws1e0">UNTERSMAYR AND JENSEN-JAROLIM<span class="_a blank"> </span><span class="ff31">1305</span></div></div><div class="c x66 y283 wa h93"><div class="t m49 xd4 h94 y284 ff33 fs6f fc0 sc0 ls1 ws1e1">time points of <span class="ff34 ws1e2">in vitr<span class="_3 blank"></span>o<span class="_a blank"> </span><span class="ff33 ws1e3">digestion in a patie<span class="_0 blank"></span>nt with gras<span class="_0 blank"></span>s pollen</span></span></div><div class="t m49 xd4 h94 y285 ff33 fs6f fc0 sc0 ls1 ws1e4">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_0 blank"></span>wed th<span class="_0 blank"></span>at gastri<span class="_0 blank"></span>c digesti<span class="_0 blank"></span>on sub<span class="_0 blank"></span>stan<span class="_0 blank"></span>tially</div><div class="t m49 xd4 h94 y286 ff33 fs6f fc0 sc0 ls1 ws1e5">decreas<span class="_0 blank"></span>ed the aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>nic capacity of the<span class="_0 blank"></span>se cross-r<span class="_0 blank"></span>eacti<span class="_3 blank"></span>ve food</div><div class="t m49 xd4 h94 y287 ff33 fs6f fc0 sc0 ls1 ws1e6">protein<span class="_0 blank"></span>s (<span class="fc10 ws1e7">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n testin<span class="_0 blank"></span>g in<span class="_a blank"> </span>pat<span class="_0 blank"></span>ients<span class="_a blank"> </span>wit<span class="_0 blank"></span>h \ufb01sh<span class="_a blank"> </span>all<span class="_0 blank"></span>ergy<span class="_a blank"> </span>wit<span class="_0 blank"></span>h</span></span></div><div class="t m49 xd4 h94 y288 ff33 fs6f fc0 sc0 ls1 ws1e8">SGF-p<span class="_0 blank"></span>redige<span class="_0 blank"></span>sted or SGF-u<span class="_0 blank"></span>ndi<span class="_0 blank"></span>gested co<span class="_0 blank"></span>d\ufb01sh all<span class="_0 blank"></span>erge<span class="_0 blank"></span>ns sho<span class="_3 blank"></span>wed a</div><div class="t m49 xd4 h94 y289 ff33 fs6f fc0 sc0 ls1 ws1e9">signi\ufb01<span class="_0 blank"></span>can<span class="_0 blank"></span>t diges<span class="_0 blank"></span>tion tim<span class="_0 blank"></span>e-d<span class="_0 blank"></span>epende<span class="_0 blank"></span>nt redu<span class="_0 blank"></span>cti<span class="_0 blank"></span>on of ind<span class="_0 blank"></span>uce<span class="_0 blank"></span>d wheal</div><div class="t m49 xd4 h94 y28a ff33 fs6f fc0 sc0 ls1 ws1ea">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>v<span class="_0 blank"></span>er<span class="_0 blank"></span>, double<span class="_0 blank"></span>-blin<span class="_0 blank"></span>d, place<span class="_0 blank"></span>bo-co<span class="_0 blank"></span>ntroll<span class="_0 blank"></span>ed, food</div><div class="t m49 xd4 h94 y28b ff33 fs6f fc0 sc0 ls1 ws1eb">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tients wit<span class="_0 blank"></span>h \ufb01sh all<span class="_0 blank"></span>ergy<span class="_9 blank"> </span>res<span class="_0 blank"></span>ulted in a 10- to</div><div class="t m49 xd4 h94 y28c ff33 fs6f fc0 sc0 ls1 ws1ec">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ated all<span class="_0 blank"></span>ergen dos<span class="_0 blank"></span>e if the \ufb01sh protein<span class="_0 blank"></span>s were pre-</div><div class="t m49 xd4 h94 y28d ff33 fs6f fc0 sc0 ls1 ws1ed">viousl<span class="_0 blank"></span>y subjected to <span class="ff34 ws1ee">in vit<span class="_0 blank"></span>r<span class="_3 blank"></span>o<span class="_f blank"> </span><span class="ff33 ws1ef">gastric dige<span class="_0 blank"></span>stion.</span></span></div><div class="t m4a xd5 h95 y28e ff33 fs70 fc10 sc0 ls1">27</div><div class="t m49 xd4 h96 y28f ff35 fs71 fc0 sc0 ls1 ws1f0">SAFETY<span class="_a blank"> </span>ISSUES<span class="_17 blank"> </span>AND<span class="_a blank"> </span>CLINICAL<span class="_17 blank"> </span>IMPLICATIONS</div><div class="t m49 xd4 h96 y290 ff35 fs71 fc0 sc0 ls1 ws1f1">FOR<span class="_17 blank"> </span>ALLERG IC<span class="_a blank"> </span>AND<span class="_17 blank"> </span>NONALLERGIC<span class="_a blank"> </span>CONSUMERS</div><div class="t m49 xd6 h94 y291 ff33 fs6f fc0 sc0 ls1 ws1f2">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m49 xd4 h94 y292 ff33 fs6f fc0 sc0 ls1 ws1f3">clinical outcome after the consumption of<span class="_a blank"> </span>a digestion-sensitiv<span class="_0 blank"></span>e</div><div class="t m49 xd4 h94 y293 ff33 fs6f fc0 sc0 ls1 ws1f4">dietary protein depends to a certain<span class="_10 blank"> </span>degree on the gastric digestiv<span class="_0 blank"></span>e</div><div class="t m49 xd4 h94 y294 ff33 fs6f fc0 sc0 ls1 ws1f5">capacity<span class="_3 blank"></span>. If the food protein is<span class="_f blank"> </span>exposed to gastric enzymes during</div><div class="t m49 xd4 h94 y295 ff33 fs6f fc0 sc0 ls1 ws1f6">transit, protein cleavage takes place, inducing either oral toler-</div><div class="t m49 xd4 h94 y296 ff33 fs6f fc0 sc0 ls1 ws1f7">ance or immune ignorance toward the ingested food protein.</div><div class="t m49 xd4 h94 y297 ff33 fs6f fc0 sc0 ls1 ws1f8">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m49 xd4 h94 y298 ff33 fs6f fc0 sc0 ls1 ws1f9">impaired digestion, such as during acid-suppression treatment,</div><div class="t m49 xd7 h94 y299 ff33 fs6f fc0 sc0 ls1 ws1fa">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m49 xd7 h94 y29a ff33 fs6f fc0 sc0 ls1 ws1fb">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m49 xd7 h94 y29b ff33 fs6f fc0 sc0 ls1 ws1fc">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m49 xd7 h94 y29c ff33 fs6f fc0 sc0 ls1 ws1fd">the allergenic capacity<span class="_9 blank"> </span>of ingested food<span class="_9 blank"> </span>proteins, whereas severe</div><div class="t m49 xd7 h94 y29d ff33 fs6f fc0 sc0 ls1 ws1fe">allergic reactions at much lower amounts of ingested food</div><div class="t m49 xd7 h94 y29e ff33 fs6f fc0 sc0 ls1 ws1ff">proteins could occur if digestion is impaired (<span class="_1 blank"> </span><span class="fc10 ws200">Fig 3</span>).</div><div class="t m49 xd8 h94 y29f ff33 fs6f fc0 sc0 ls1 ws201">The revie<span class="_0 blank"></span>wed data<span class="_a blank"> </span>indicate<span class="_a blank"> </span>that<span class="_18 blank"> </span>the current<span class="_a blank"> </span>concept<span class="_a blank"> </span>of food</div><div class="t m49 xd7 h94 y2a0 ff33 fs6f fc0 sc0 ls1 ws202">allergen classi\ufb01cation into class 1<span class="_f blank"> </span>(true food allergen) and<span class="_f blank"> </span>class 2</div><div class="t m49 xd7 h94 y2a1 ff33 fs6f fc0 sc0 ls1 ws203">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m49 xd7 h94 y2a2 ff33 fs6f fc0 sc0 ls1 ws204">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m49 xd7 h94 y2a3 ff33 fs6f fc0 sc0 ls1 ws205">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m49 xd7 h94 y2a4 ff33 fs6f fc0 sc0 ls1 ws206">and<span class="_10 blank"> </span>consumers\u2019 safety<span class="_f blank"> </span>might<span class="_10 blank"> </span>be<span class="_f blank"> </span>en<span class="_0 blank"></span>visaged<span class="_10 blank"> </span>(<span class="fc10 ws207">T<span class="_3 blank"></span>able II<span class="fc0 ws208">). It should be</span></span></div><div class="t m49 xd7 h97 y2a5 ff35 fs72 fc0 sc0 ls1 ws209">FIG 3.<span class="_a blank"> </span><span class="ff36 ws20a">The gate-keeping function of the stomach in the sensitization and</span></div><div class="t m49 xd7 h97 y2a6 ff36 fs72 fc0 sc0 ls1 ws20b">effector phase of food allergy. The fate of a dietary protein<span class="_10 blank"> </span>depends<span class="_f blank"> </span>on the</div><div class="t m49 xd7 h97 y2a7 ff36 fs72 fc0 sc0 ls1 ws20c">gastric<span class="_a blank"> </span>digestive<span class="_17 blank"> </span>functio n<span class="_a blank"> </span>mainly<span class="_a blank"> </span>accomplished<span class="_a blank"> </span>by<span class="_17 blank"> </span>the<span class="_a blank"> </span>gastric<span class="_a blank"> </span>protease</div><div class="t m49 xd7 h97 y2a8 ff36 fs72 fc0 sc0 ls1 ws20d">pepsin. If the protein<span class="_17 blank"> </span>structure is destroyed beca<span class="_1 blank"> </span>use of proteolysis, oral</div><div class="t m49 xd7 h97 y2a9 ff36 fs72 fc0 sc0 ls1 ws20e">tolerance<span class="_8 blank"> </span>or<span class="_8 blank"> </span>immune<span class="_8 blank"> </span>ignorance<span class="_8 blank"> </span>and<span class="_8 blank"> </span>a<span class="_8 blank"> </span>reduce d<span class="_8 blank"> </span>allerge nic<span class="_8 blank"> </span>potential<span class="_10 blank"> </span>might<span class="_6 blank"> </span>be</div><div class="t m49 xd7 h97 y2aa ff36 fs72 fc0 sc0 ls1 ws20f">the<span class="_2e blank"> </span>result.<span class="_22 blank"> </span>However,<span class="_22 blank"> </span>when<span class="_2e blank"> </span>gastric<span class="_22 blank"> </span>digestion<span class="_22 blank"> </span>is<span class="_2e blank"> </span>impaired<span class="_22 blank"> </span>(eg,<span class="_2e blank"> </span>under</div><div class="t m49 xd7 h97 y2ab ff36 fs72 fc0 sc0 ls1 ws210">hypoacidic<span class="_f blank"> </span>gastric<span class="_f blank"> </span>conditions),<span class="_f blank"> </span>digestion-labile<span class="_f blank"> </span>proteins<span class="_f blank"> </span>might<span class="_f blank"> </span>trigger<span class="_f blank"> </span>oral</div><div class="t m49 xd7 h97 y2ac ff36 fs72 fc0 sc0 ls1 ws211">sensitization or severe allergic symptoms<span class="_9 blank"> </span>in a previousl<span class="_1 blank"> </span>y sensitized indi-</div><div class="t m49 xd7 h97 y2ad ff36 fs72 fc0 sc0 ls1 ws212">vidual.<span class="_17 blank"> </span>The<span class="_17 blank"> </span>\ufb01gure<span class="_17 blank"> </span>was<span class="_17 blank"> </span>created<span class="_a blank"> </span>with<span class="_17 blank"> </span>the<span class="_17 blank"> </span>structural<span class="_17 blank"> </span>information<span class="_17 blank"> </span>provided</div><div class="t m49 xd7 h97 y2ae ff36 fs72 fc0 sc0 ls1 ws213">from<span class="_a blank"> </span>Research<span class="_a blank"> </span>Collaboratory<span class="_a blank"> </span>for<span class="_a blank"> </span>Structural<span class="_a blank"> </span>Bioinformatics<span class="_a blank"> </span>Protein<span class="_a blank"> </span>Data</div><div class="t m49 xd7 h97 y2af ff36 fs72 fc0 sc0 ls1 ws213">Bank<span class="_10 blank"> </span>accession<span class="_f blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_10 blank"> </span>and<span class="_f blank"> </span>5PEP.</div><div class="t m49 xd4 h97 y2b0 ff35 fs72 fc0 sc0 ls1 ws214">FIG<span class="_18 blank"> </span>2. <span class="ff36 ws20e">Reduced<span class="_e blank"> </span>allergenicity<span class="_e blank"> </span>of<span class="_18 blank"> </span>melo n<span class="_e blank"> </span>allergens<span class="_18 blank"> </span>after<span class="_e blank"> </span>incubation<span class="_e blank"> </span>with</span></div><div class="t m49 xd4 h97 y2b1 ff36 fs72 fc0 sc0 ls1 ws215">gastric enzymes. After subjection to<span class="_10 blank"> </span>SGF, melon allergens induc<span class="_1 blank"> </span>e a smaller</div><div class="t m49 xd4 h97 y2b2 ff36 fs72 fc0 sc0 ls1 ws216">wheal reaction in a patient with melon<span class="_17 blank"> </span>allergy compared with the undi-</div><div class="t m49 xd4 h97 y2b3 ff36 fs72 fc0 sc0 ls1 ws217">gested<span class="_a blank"> </span>extract.<span class="_a blank"> </span>The<span class="_18 blank"> </span>alteration<span class="_a blank"> </span>of<span class="_a blank"> </span>skin<span class="_18 blank"> </span>reactivity<span class="_a blank"> </span>was<span class="_a blank"> </span>dependen t<span class="_a blank"> </span>on<span class="_18 blank"> </span>the</div><div class="t m49 xd4 h97 y2b4 ff36 fs72 fc0 sc0 ls1 ws218">incubation<span class="_f blank"> </span>time<span class="_10 blank"> </span>with<span class="_f blank"> </span>the<span class="_10 blank"> </span>proteolytic<span class="_f blank"> </span>enzymes.</div><div class="t m49 xd7 h98 y2b5 ff35 fs73 fc0 sc0 ls1 ws219">TABLE II. <span class="ff36 ws21a">Key concepts and<span class="_9 blank"> </span>safety implications</span></div><div class="t m49 xd7 h99 y2b6 ff33 fs73 fc0 sc0 ls1 ws21b">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m49 xd9 h99 y2b7 ff33 fs73 fc0 sc0 ls1 ws21c">safety tests for novel (eg, genetically modi\ufb01ed) food compounds.</div><div class="t m49 xd7 h99 y2b8 ff33 fs73 fc0 sc0 ls1 ws21d">Patients should be advised that<span class="_9 blank"> </span>threshold levels might vary in situations of</div><div class="t m49 xd9 h99 y2b9 ff33 fs73 fc0 sc0 ls1 ws21e">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current efforts to</div><div class="t m49 xd9 h99 y2ba ff33 fs73 fc0 sc0 ls1 ws21f">de\ufb01ne no-observed-adv<span class="_0 blank"></span>erse-ef<span class="_0 blank"></span>fect lev<span class="_0 blank"></span>els for food allergens.</div><div class="t m49 xd7 h99 y2bb ff33 fs73 fc0 sc0 ls1 ws220">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m49 xd9 h99 y2bc ff33 fs73 fc0 sc0 ls1 ws21f">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m49 xd9 h99 y2bd ff33 fs73 fc0 sc0 ls1 ws221">food ingestion.</div><div class="t m49 xd4 h9a y2be ff36 fs74 fc0 sc0 ls1 ws222">J ALLERGY CLIN IMMUNOL</div><div class="t m49 xd4 h9a y2bf ff36 fs74 fc0 sc0 ls1 ws223">VOLUME 121, NUMBER 6</div><div class="t m49 xa5 h98 y2be ff36 fs73 fc0 sc0 ls1 ws224">UNTERSMAYR AND JENSEN-JAROLIM<span class="_a blank"> </span><span class="ff35">1305</span></div></div><div class="c x64 y2c0 wb h9b"><div class="t m4b xda h9c y2c1 ff37 fs75 fc0 sc0 ls1 ws225">time points of <span class="ff38 ws226">in vitr<span class="_3 blank"></span>o<span class="_18 blank"> </span><span class="ff37 ws227">digestio<span class="_0 blank"></span>n in a patient with<span class="_a blank"> </span>grass pollen</span></span></div><div class="t m4b xda h9c y2c2 ff37 fs75 fc0 sc0 ls1 ws228">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_3 blank"></span>wed that gastric dige<span class="_0 blank"></span>sti<span class="_0 blank"></span>on subst<span class="_0 blank"></span>antia<span class="_0 blank"></span>lly</div><div class="t m4b xda h9c y2c3 ff37 fs75 fc0 sc0 ls1 ws229">decre<span class="_0 blank"></span>ased the aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>nic capac<span class="_0 blank"></span>ity of these cross<span class="_0 blank"></span>-reac<span class="_0 blank"></span>ti<span class="_3 blank"></span>ve food</div><div class="t m4b xda h9c y2c4 ff37 fs75 fc0 sc0 ls1 ws22a">prote<span class="_0 blank"></span>ins (<span class="fc10 ws22b">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n tes<span class="_0 blank"></span>tin<span class="_0 blank"></span>g in pat<span class="_0 blank"></span>ients wit<span class="_0 blank"></span>h \ufb01<span class="_0 blank"></span>sh all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy wit<span class="_0 blank"></span>h</span></span></div><div class="t m4b xda h9c y2c5 ff37 fs75 fc0 sc0 ls1 ws22c">SGF-p<span class="_0 blank"></span>redige<span class="_0 blank"></span>sted or SGF<span class="_0 blank"></span>-undi<span class="_0 blank"></span>gested co<span class="_0 blank"></span>d\ufb01<span class="_0 blank"></span>sh aller<span class="_0 blank"></span>gens sho<span class="_3 blank"></span>wed a</div><div class="t m4b xda h9c y2c6 ff37 fs75 fc0 sc0 ls1 ws22d">signi\ufb01<span class="_3 blank"></span>cant digestio<span class="_0 blank"></span>n tim<span class="_0 blank"></span>e-depe<span class="_0 blank"></span>ndent<span class="_9 blank"> </span>reducti<span class="_0 blank"></span>on of<span class="_9 blank"> </span>induced wheal</div><div class="t m4b xda h9c y2c7 ff37 fs75 fc0 sc0 ls1 ws22e">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>v<span class="_0 blank"></span>er<span class="_3 blank"></span>,<span class="_2f blank"> </span>double<span class="_0 blank"></span>-blin<span class="_0 blank"></span>d, placebo-<span class="_0 blank"></span>co<span class="_0 blank"></span>ntroll<span class="_0 blank"></span>ed, food</div><div class="t m4b xda h9c y2c8 ff37 fs75 fc0 sc0 ls1 ws22f">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tie<span class="_0 blank"></span>nts with \ufb01<span class="_0 blank"></span>sh aller<span class="_0 blank"></span>gy res<span class="_0 blank"></span>ulted in a 10- to</div><div class="t m4b xda h9c y2c9 ff37 fs75 fc0 sc0 ls1 ws230">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ate<span class="_0 blank"></span>d aller<span class="_0 blank"></span>gen dose if the \ufb01sh prot<span class="_0 blank"></span>eins were pre<span class="_0 blank"></span>-</div><div class="t m4b xda h9c y2ca ff37 fs75 fc0 sc0 ls1 ws231">viousl<span class="_0 blank"></span>y subjec<span class="_0 blank"></span>ted to <span class="ff38 ws232">in vitr<span class="_3 blank"></span>o<span class="_9 blank"> </span><span class="ff37 ws233">gas<span class="_0 blank"></span>tri<span class="_0 blank"></span>c digesti<span class="_0 blank"></span>on.</span></span></div><div class="t m4c xdb h9d y2cb ff37 fs76 fc10 sc0 ls1">27</div><div class="t m4b xda h9e y2cc ff39 fs77 fc0 sc0 ls1 ws234">SAFETY<span class="_a blank"> </span>ISSUES<span class="_a blank"> </span>AND<span class="_a blank"> </span>CLINICAL<span class="_a blank"> </span>IMPLICATIONS</div><div class="t m4b xda h9e y2cd ff39 fs77 fc0 sc0 ls1 ws235">FOR<span class="_a blank"> </span>ALLERGIC<span class="_a blank"> </span>AND<span class="_a blank"> </span>NONALLERGIC<span class="_a blank"> </span>CONSUMERS</div><div class="t m4b xdc h9c y2ce ff37 fs75 fc0 sc0 ls1 ws236">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m4b xda h9c y2cf ff37 fs75 fc0 sc0 ls1 ws237">clinical outcome after the consumption of<span class="_a blank"> </span>a digestion-sensitive</div><div class="t m4b xda h9c y2d0 ff37 fs75 fc0 sc0 ls1 ws238">dietary protein depends to a certain<span class="_10 blank"> </span>degree on the gastric digestive</div><div class="t m4b xda h9c y2d1 ff37 fs75 fc0 sc0 ls1 ws239">capacity<span class="_3 blank"></span>. If the food protein is exposed to gastric enzymes<span class="_f blank"> </span>during</div><div class="t m4b xda h9c y2d2 ff37 fs75 fc0 sc0 ls1 ws23a">transit, protein cleav<span class="_0 blank"></span>age takes place, inducing either oral toler-</div><div class="t m4b xda h9c y2d3 ff37 fs75 fc0 sc0 ls1 ws23b">ance or immune ignorance toward the ingested food protein.</div><div class="t m4b xda h9c y2d4 ff37 fs75 fc0 sc0 ls1 ws23c">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m4b xda h9c y2d5 ff37 fs75 fc0 sc0 ls1 ws23d">impaired digestion, such as during acid-suppression treatment,</div><div class="t m4b xdd h9c y2d6 ff37 fs75 fc0 sc0 ls1 ws23e">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m4b xdd h9c y2d7 ff37 fs75 fc0 sc0 ls1 ws23f">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m4b xdd h9c y2d8 ff37 fs75 fc0 sc0 ls1 ws240">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m4b xdd h9c y2d9 ff37 fs75 fc0 sc0 ls1 ws241">the allergenic capacity<span class="_9 blank"> </span>of ingested<span class="_9 blank"> </span>food proteins,<span class="_9 blank"> </span>whereas severe</div><div class="t m4b xdd h9c y2da ff37 fs75 fc0 sc0 ls1 ws242">allergic reactions at much lower amounts of ingested<span class="_19 blank"> </span>food</div><div class="t m4b xdd h9c y2db ff37 fs75 fc0 sc0 ls1 ws243">proteins could occur if digestion is impaired (<span class="_1 blank"> </span><span class="fc10 ws244">Fig 3</span>).</div><div class="t m4b xde h9c y2dc ff37 fs75 fc0 sc0 ls1 ws245">The revie<span class="_0 blank"></span>wed data<span class="_18 blank"> </span>indicate<span class="_18 blank"> </span>that<span class="_18 blank"> </span>the current<span class="_18 blank"> </span>concept<span class="_18 blank"> </span>of food</div><div class="t m4b xdd h9c y2dd ff37 fs75 fc0 sc0 ls1 ws246">allergen classi\ufb01cation into class 1<span class="_f blank"> </span>(true<span class="_f blank"> </span>food allergen) and<span class="_f blank"> </span>class<span class="_f blank"> </span>2</div><div class="t m4b xdd h9c y2de ff37 fs75 fc0 sc0 ls1 ws247">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m4b xdd h9c y2df ff37 fs75 fc0 sc0 ls1 ws248">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m4b xdd h9c y2e0 ff37 fs75 fc0 sc0 ls1 ws249">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m4b xdd h9c y2e1 ff37 fs75 fc0 sc0 ls1 ws24a">and<span class="_f blank"> </span>consumers\u2019 safety<span class="_10 blank"> </span>might<span class="_f blank"> </span>be<span class="_f blank"> </span>en<span class="_0 blank"></span>visaged<span class="_f blank"> </span>(<span class="fc10 ws24b">T<span class="_3 blank"></span>able II<span class="fc0 ws24c">). It should be</span></span></div><div class="t m4b xdd h9f y2e2 ff39 fs78 fc0 sc0 ls1 ws24d">FIG 3.<span class="_a blank"> </span><span class="ff3a ws24e">The gate-keeping function of the stomach in the sensiti<span class="_1 blank"> </span>zation and</span></div><div class="t m4b xdd h9f y2e3 ff3a fs78 fc0 sc0 ls1 ws24f">effector phase of food allergy. The fate of a dietary<span class="_f blank"> </span>protein depends on the</div><div class="t m4b xdd h9f y2e4 ff3a fs78 fc0 sc0 ls1 ws250">gastric<span class="_a blank"> </span>digestive<span class="_a blank"> </span>functio n<span class="_18 blank"> </span>mainly<span class="_a blank"> </span>accomplished<span class="_18 blank"> </span>by<span class="_a blank"> </span>the<span class="_a blank"> </span>gastric<span class="_18 blank"> </span>protease</div><div class="t m4b xdd h9f y2e5 ff3a fs78 fc0 sc0 ls1 ws251">pepsin. If the protein<span class="_17 blank"> </span>structure<span class="_a blank"> </span>is destroyed because of proteolysis, oral</div><div class="t m4b xdd h9f y2e6 ff3a fs78 fc0 sc0 ls1 ws252">tolerance<span class="_8 blank"> </span>or<span class="_10 blank"> </span>immune<span class="_8 blank"> </span>ignorance<span class="_8 blank"> </span>and<span class="_10 blank"> </span>a<span class="_6 blank"> </span>reduce d<span class="_10 blank"> </span>allergenic<span class="_8 blank"> </span>potential<span class="_8 blank"> </span>might<span class="_10 blank"> </span>be</div><div class="t m4b xdd h9f y2e7 ff3a fs78 fc0 sc0 ls1 ws253">the<span class="_22 blank"> </span>result.<span class="_1a blank"> </span>However,<span class="_1a blank"> </span>when<span class="_22 blank"> </span>gastric<span class="_1a blank"> </span>digestion<span class="_1a blank"> </span>is<span class="_22 blank"> </span>impaired<span class="_1a blank"> </span>(eg,<span class="_22 blank"> </span>under</div><div class="t m4b xdd h9f y2e8 ff3a fs78 fc0 sc0 ls1 ws254">hypoacidic<span class="_f blank"> </span>gastric<span class="_9 blank"> </span>conditions),<span class="_f blank"> </span>digestion-labile<span class="_f blank"> </span>protein s<span class="_9 blank"> </span>might<span class="_f blank"> </span>trigger<span class="_f blank"> </span>oral</div><div class="t m4b xdd h9f y2e9 ff3a fs78 fc0 sc0 ls1 ws255">sensitization or severe allergic sympt<span class="_1 blank"> </span>oms in a previously sensitized indi-</div><div class="t m4b xdd h9f y2ea ff3a fs78 fc0 sc0 ls1 ws256">vidual.<span class="_17 blank"> </span>The<span class="_a blank"> </span>\ufb01gure<span class="_a blank"> </span>was<span class="_17 blank"> </span>created<span class="_a blank"> </span>with<span class="_17 blank"> </span>the<span class="_a blank"> </span>structural<span class="_17 blank"> </span>informatio<span class="_1 blank"> </span>n<span class="_a blank"> </span>provided</div><div class="t m4b xdd h9f y2eb ff3a fs78 fc0 sc0 ls1 ws257">from<span class="_a blank"> </span>Research<span class="_18 blank"> </span>Collaboratory<span class="_18 blank"> </span>for<span class="_a blank"> </span>Structural<span class="_18 blank"> </span>Bioinforma tics<span class="_18 blank"> </span>Protein<span class="_18 blank"> </span>Data</div><div class="t m4b xdd h9f y2ec ff3a fs78 fc0 sc0 ls1 ws257">Bank<span class="_f blank"> </span>accession<span class="_f blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_f blank"> </span>and<span class="_f blank"> </span>5PEP.</div><div class="t m4b xda h9f y2ed ff39 fs78 fc0 sc0 ls1 ws258">FIG<span class="_e blank"> </span>2. <span class="ff3a ws252">Reduced<span class="_15 blank"> </span>allergenicity<span class="_e blank"> </span>of<span class="_15 blank"> </span>melon<span class="_e blank"> </span>allergens<span class="_15 blank"> </span>after<span class="_15 blank"> </span>incubation<span class="_e blank"> </span>with</span></div><div class="t m4b xda h9f y2ee ff3a fs78 fc0 sc0 ls1 ws259">gastric enzymes. After subjection<span class="_10 blank"> </span>to SGF, melon<span class="_10 blank"> </span>allergens induc<span class="_1 blank"> </span>e a smaller</div><div class="t m4b xda h9f y2ef ff3a fs78 fc0 sc0 ls1 ws25a">wheal reaction in a patient with melon<span class="_a blank"> </span>allergy compared with the undi-</div><div class="t m4b xda h9f y2f0 ff3a fs78 fc0 sc0 ls1 ws25b">gested<span class="_18 blank"> </span>extract.<span class="_18 blank"> </span>The<span class="_18 blank"> </span>alteration<span class="_18 blank"> </span>of<span class="_18 blank"> </span>skin<span class="_18 blank"> </span>reactivity<span class="_e blank"> </span>was<span class="_a blank"> </span>dependen t<span class="_18 blank"> </span>on<span class="_18 blank"> </span>the</div><div class="t m4b xda h9f y2f1 ff3a fs78 fc0 sc0 ls1 ws25c">incubation<span class="_f blank"> </span>time<span class="_f blank"> </span>with<span class="_f blank"> </span>the<span class="_f blank"> </span>proteolytic<span class="_f blank"> </span>enzymes.</div><div class="t m4b xdd ha0 y2f2 ff39 fs79 fc0 sc0 ls1 ws25d">TABLE II. <span class="ff3a ws25e">Key concepts and<span class="_17 blank"> </span>safety implications</span></div><div class="t m4b xdd ha1 y2f3 ff37 fs79 fc0 sc0 ls1 ws25f">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m4b xdf ha1 y2f4 ff37 fs79 fc0 sc0 ls1 ws260">safety tests for novel (eg, genetically modi\ufb01<span class="_0 blank"></span>ed) food compounds.</div><div class="t m4b xdd ha1 y2f5 ff37 fs79 fc0 sc0 ls1 ws261">Patients should be advised that<span class="_17 blank"> </span>threshold le<span class="_0 blank"></span>vels might v<span class="_0 blank"></span>ary in situations of</div><div class="t m4b xdf ha1 y2f6 ff37 fs79 fc0 sc0 ls1 ws262">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current ef<span class="_0 blank"></span>forts to</div><div class="t m4b xdf ha1 y2f7 ff37 fs79 fc0 sc0 ls1 ws263">de\ufb01ne no-observ<span class="_0 blank"></span>ed-adverse-ef<span class="_0 blank"></span>fect le<span class="_0 blank"></span>vels for food allergens.</div><div class="t m4b xdd ha1 y2f8 ff37 fs79 fc0 sc0 ls1 ws264">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m4b xdf ha1 y2f9 ff37 fs79 fc0 sc0 ls1 ws263">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m4b xdf ha1 y2fa ff37 fs79 fc0 sc0 ls1 ws265">food ingestion.</div><div class="t m4b xda ha2 y2fb ff3a fs7a fc0 sc0 ls1 ws266">J ALLERGY CLIN IMMUNOL</div><div class="t m4b xda ha2 y2fc ff3a fs7a fc0 sc0 ls1 ws267">VOLUME 121, NUMBER 6</div><div class="t m4b xe0 ha0 y2fb ff3a fs79 fc0 sc0 ls1 ws268">UNTERSMAYR AND JENSEN-JAROLIM<span class="_18 blank"> </span><span class="ff39">1305</span></div></div><div class="c x3 yc w2 h4"><div class="t m1 x79 ha3 y2fd ff4 fs2 fc1 sc0 ls9e wsb">pH = 5</div><div class="t m1 xc ha3 y2fe ff4 fs2 fc1 sc0 ls1 ws4c">Sensibilização</div><div class="t m1 x5 ha3 y2ff ff3b fs2 fc1 sc0 ls1 ws269">é<span class="ff4 ws4c">Sintomas</span></div><div class="t m1 xe1 ha3 y2fe ff4 fs2 fce sc0 ls1 ws4c">T<span class="_26 blank"></span>olerância</div><div class="t m1 xe2 ha3 y2ff ff3b fs2 fce sc0 ls1 ws269">ê<span class="ff4 ws4c">Alergenicidade</span></div><div class="t m1 xce ha3 y2fd ff4 fs2 fce sc0 ls9e wsb">pH = 2</div></div><div class="c xe3 y300 wb ha4"><div class="t m4d x87 ha5 y301 ff3c fs7b fc0 sc0 ls1 ws26a">time points of <span class="ff3d ws26b">in vitr<span class="_3 blank"></span>o<span class="_18 blank"> </span><span class="ff3c ws26c">digestio<span class="_0 blank"></span>n in a patient with<span class="_a blank"> </span>grass poll<span class="_0 blank"></span>en</span></span></div><div class="t m4d x87 ha5 y302 ff3c fs7b fc0 sc0 ls1 ws26d">and melon all<span class="_0 blank"></span>er<span class="_0 blank"></span>gy sho<span class="_3 blank"></span>wed that gastric dige<span class="_0 blank"></span>sti<span class="_0 blank"></span>on subst<span class="_0 blank"></span>antia<span class="_0 blank"></span>lly</div><div class="t m4d x87 ha5 y303 ff3c fs7b fc0 sc0 ls1 ws26e">decre<span class="_0 blank"></span>ased the aller<span class="_0 blank"></span>ge<span class="_0 blank"></span>nic capac<span class="_0 blank"></span>ity of these cross<span class="_0 blank"></span>-reac<span class="_0 blank"></span>ti<span class="_0 blank"></span>v<span class="_0 blank"></span>e food</div><div class="t m4d x87 ha5 y304 ff3c fs7b fc0 sc0 ls1 ws26f">prote<span class="_0 blank"></span>ins (<span class="fc10 ws270">Fi<span class="_0 blank"></span>g 2<span class="fc0">). Ski<span class="_0 blank"></span>n tes<span class="_0 blank"></span>ting in<span class="_a blank"> </span>patien<span class="_0 blank"></span>ts wit<span class="_0 blank"></span>h \ufb01sh<span class="_a blank"> </span>aller<span class="_0 blank"></span>gy wit<span class="_0 blank"></span>h</span></span></div><div class="t m4d x87 ha5 y305 ff3c fs7b fc0 sc0 ls1 ws271">SGF-p<span class="_0 blank"></span>redige<span class="_0 blank"></span>sted or SGF<span class="_0 blank"></span>-undi<span class="_0 blank"></span>gested co<span class="_0 blank"></span>d\ufb01<span class="_0 blank"></span>sh aller<span class="_0 blank"></span>gens sho<span class="_3 blank"></span>wed a</div><div class="t m4d x87 ha5 y306 ff3c fs7b fc0 sc0 ls1 ws272">signi\ufb01<span class="_3 blank"></span>cant digestio<span class="_0 blank"></span>n tim<span class="_0 blank"></span>e-depe<span class="_0 blank"></span>ndent<span class="_9 blank"> </span>reducti<span class="_0 blank"></span>on of<span class="_9 blank"> </span>induced wh<span class="_0 blank"></span>eal</div><div class="t m4d x87 ha5 y307 ff3c fs7b fc0 sc0 ls1 ws273">react<span class="_0 blank"></span>ion. Moreo<span class="_0 blank"></span>v<span class="_0 blank"></span>er<span class="_3 blank"></span>,<span class="_2f blank"> </span>double<span class="_0 blank"></span>-blin<span class="_0 blank"></span>d, place<span class="_0 blank"></span>bo-co<span class="_0 blank"></span>ntr<span class="_0 blank"></span>olled<span class="_0 blank"></span>, food</div><div class="t m4d x87 ha5 y308 ff3c fs7b fc0 sc0 ls1 ws274">chall<span class="_0 blank"></span>enges in these pa<span class="_0 blank"></span>tie<span class="_0 blank"></span>nts with \ufb01<span class="_0 blank"></span>sh aller<span class="_0 blank"></span>gy result<span class="_0 blank"></span>ed in a 10- to</div><div class="t m4d x87 ha5 y309 ff3c fs7b fc0 sc0 ls1 ws275">30-fo<span class="_0 blank"></span>ld higher toler<span class="_0 blank"></span>ate<span class="_0 blank"></span>d aller<span class="_0 blank"></span>gen dose if the \ufb01sh prot<span class="_0 blank"></span>eins were pre<span class="_0 blank"></span>-</div><div class="t m4d x87 ha5 y30a ff3c fs7b fc0 sc0 ls1 ws276">viousl<span class="_0 blank"></span>y subjec<span class="_0 blank"></span>ted to <span class="ff3d ws277">in vitr<span class="_3 blank"></span>o<span class="_f blank"> </span><span class="ff3c ws278">gastric dige<span class="_0 blank"></span>stion.</span></span></div><div class="t m4e xe4 ha6 y30b ff3c fs7c fc10 sc0 ls1">27</div><div class="t m4f x87 ha7 y30c ff3e fs7d fc0 sc0 ls1 ws279">SAFETY<span class="_a blank"> </span>ISSUES<span class="_a blank"> </span>AND<span class="_a blank"> </span>CLINICAL<span class="_a blank"> </span>IMPLICATIONS</div><div class="t m4f x87 ha7 y30d ff3e fs7d fc0 sc0 ls1 ws27a">FOR<span class="_a blank"> </span>ALLERGIC<span class="_a blank"> </span>AND<span class="_a blank"> </span>NONALLERGIC<span class="_a blank"> </span>CONSUMERS</div><div class="t m4f xe5 ha5 y30e ff3c fs7b fc0 sc0 ls1 ws27b">The data revie<span class="_0 blank"></span>wed here suggest that the immunologic or</div><div class="t m4f x87 ha5 y30f ff3c fs7b fc0 sc0 ls1 ws27c">clinical outcome after the consumption of<span class="_a blank"> </span>a digestion-sensitive</div><div class="t m4f x87 ha5 y310 ff3c fs7b fc0 sc0 ls1 ws27d">dietary protein depends to a certain<span class="_10 blank"> </span>degree on the gastric digestive</div><div class="t m4f x87 ha5 y311 ff3c fs7b fc0 sc0 ls1 ws27e">capacity<span class="_3 blank"></span>. If the food protein is exposed to gastric enzymes<span class="_f blank"> </span>during</div><div class="t m4f x87 ha5 y312 ff3c fs7b fc0 sc0 ls1 ws27f">transit, protein cleavage takes place, inducing either oral toler-</div><div class="t m4f x87 ha5 y313 ff3c fs7b fc0 sc0 ls1 ws280">ance or immune ignorance toward the ingested food protein.</div><div class="t m4f x87 ha5 y314 ff3c fs7b fc0 sc0 ls1 ws281">Howe<span class="_0 blank"></span>ver<span class="_3 blank"></span>, if proteins persist during the gastric transit because of</div><div class="t m4f x87 ha5 y315 ff3c fs7b fc0 sc0 ls1 ws282">impaired digestion, such as during acid-suppression treatment,</div><div class="t m4f x99 ha5 y316 ff3c fs7b fc0 sc0 ls1 ws283">IgE-mediated food allergy can be induced. Gastric digestion</div><div class="t m4f x99 ha5 y317 ff3c fs7b fc0 sc0 ls1 ws284">might also in\ufb02uence the extent of reactivity in already sensitized</div><div class="t m4f x99 ha5 y318 ff3c fs7b fc0 sc0 ls1 ws285">patients. Physiologic gastric proteolysis substantially decreases</div><div class="t m4f x99 ha5 y319 ff3c fs7b fc0 sc0 ls1 ws286">the allergenic capacity<span class="_9 blank"> </span>of ingested food<span class="_9 blank"> </span>proteins, whereas<span class="_9 blank"> </span>severe</div><div class="t m4f x99 ha5 y31a ff3c fs7b fc0 sc0 ls1 ws287">allergic reactions at much lower amounts of ingested<span class="_19 blank"> </span>food</div><div class="t m4f x99 ha5 y31b ff3c fs7b fc0 sc0 ls1 ws288">proteins could occur if digestion is impaired (<span class="_1 blank"> </span><span class="fc10 ws289">Fig 3</span>).</div><div class="t m4f xe6 ha5 y31c ff3c fs7b fc0 sc0 ls1 ws28a">The revie<span class="_0 blank"></span>wed data<span class="_18 blank"> </span>indicate that<span class="_18 blank"> </span>the<span class="_18 blank"> </span>current<span class="_18 blank"> </span>concept of food</div><div class="t m4f x99 ha5 y31d ff3c fs7b fc0 sc0 ls1 ws28b">allergen classi\ufb01cation into class 1<span class="_f blank"> </span>(true food<span class="_f blank"> </span>allergen) and<span class="_f blank"> </span>class 2</div><div class="t m4f x99 ha5 y31e ff3c fs7b fc0 sc0 ls1 ws28c">(labile food proteins) is misleading and thus should be reconsid-</div><div class="t m4f x99 ha5 y31f ff3c fs7b fc0 sc0 ls1 ws28d">ered. W<span class="_3 blank"></span>e suggest introducing the concept of allergen persistence</div><div class="t m4f x99 ha5 y320 ff3c fs7b fc0 sc0 ls1 ws28e">in food allergen terminology<span class="_3 blank"></span>. Serious implications for patients\u2019</div><div class="t m4f x99 ha5 y321 ff3c fs7b fc0 sc0 ls1 ws28f">and<span class="_f blank"> </span>consumers\u2019 safety<span class="_10 blank"> </span>might<span class="_f blank"> </span>be<span class="_f blank"> </span>en<span class="_0 blank"></span>visaged<span class="_10 blank"> </span>(<span class="fc10 ws290">T<span class="_3 blank"></span>able II<span class="fc0 ws291">). It<span class="_f blank"> </span>should be</span></span></div><div class="t m4f x99 ha8 y322 ff3e fs7e fc0 sc0 ls1 ws292">FIG 3.<span class="_a blank"> </span><span class="ff3f ws293">The gate-keeping function of the stomach in the sensitization and</span></div><div class="t m4f x99 ha8 y323 ff3f fs7e fc0 sc0 ls1 ws294">effector phase of food allergy. The fate of a dietary<span class="_f blank"> </span>protein depends on the</div><div class="t m4f x99 ha8 y324 ff3f fs7e fc0 sc0 ls1 ws295">gastric<span class="_a blank"> </span>digestive<span class="_a blank"> </span>function<span class="_18 blank"> </span>mainly<span class="_a blank"> </span>accomplished<span class="_a blank"> </span>by<span class="_a blank"> </span>the<span class="_18 blank"> </span>gastric<span class="_a blank"> </span>protease</div><div class="t m4f x99 ha8 y325 ff3f fs7e fc0 sc0 ls1 ws296">pepsin. If the protein<span class="_17 blank"> </span>structure<span class="_17 blank"> </span>is destroyed<span class="_17 blank"> </span>beca<span class="_1 blank"> </span>use of proteolysis, oral</div><div class="t m4f x99 ha8 y326 ff3f fs7e fc0 sc0 ls1 ws297">tolerance<span class="_8 blank"> </span>or<span class="_8 blank"> </span>immune<span class="_10 blank"> </span>ignorance<span class="_8 blank"> </span>and<span class="_8 blank"> </span>a<span class="_10 blank"> </span>reduced<span class="_8 blank"> </span>allergenic<span class="_8 blank"> </span>potential<span class="_8 blank"> </span>might<span class="_10 blank"> </span>be</div><div class="t m4f x99 ha8 y327 ff3f fs7e fc0 sc0 ls1 ws298">the<span class="_22 blank"> </span>result.<span class="_1a blank"> </span>However,<span class="_22 blank"> </span>when<span class="_1a blank"> </span>gastric<span class="_22 blank"> </span>digestion<span class="_1a blank"> </span>is<span class="_22 blank"> </span>impaired<span class="_22 blank"> </span>(eg,<span class="_1a blank"> </span>under</div><div class="t m4f x99 ha8 y328 ff3f fs7e fc0 sc0 ls1 ws299">hypoacidic<span class="_f blank"> </span>gastric<span class="_f blank"> </span>condi tions),<span class="_9 blank"> </span>digestion-labile<span class="_f blank"> </span>proteins<span class="_f blank"> </span>might<span class="_f blank"> </span>trigger<span class="_9 blank"> </span>oral</div><div class="t m4f x99 ha8 y329 ff3f fs7e fc0 sc0 ls1 ws29a">sensitization or severe allergic sympt<span class="_1 blank"> </span>oms in a previously sensitized indi-</div><div class="t m4f x99 ha8 y32a ff3f fs7e fc0 sc0 ls1 ws29b">vidual.<span class="_17 blank"> </span>The<span class="_a blank"> </span>\ufb01gure<span class="_17 blank"> </span>was<span class="_a blank"> </span>created<span class="_17 blank"> </span>with<span class="_a blank"> </span>the<span class="_17 blank"> </span>structural<span class="_a blank"> </span>information<span class="_17 blank"> </span>provided</div><div class="t m4f x99 ha8 y32b ff3f fs7e fc0 sc0 ls1 ws29c">from<span class="_a blank"> </span>Research<span class="_18 blank"> </span>Collaboratory<span class="_18 blank"> </span>for<span class="_a blank"> </span>Structural<span class="_18 blank"> </span>Bioinformatics<span class="_a blank"> </span>Protein<span class="_18 blank"> </span>Data</div><div class="t m4f x99 ha8 y32c ff3f fs7e fc0 sc0 ls1 ws29c">Bank<span class="_f blank"> </span>accession<span class="_f blank"> </span>numbers<span class="_f blank"> </span>3PSG<span class="_10 blank"> </span>and<span class="_f blank"> </span>5PEP.</div><div class="t m4f x87 ha8 y32d ff3e fs7e fc0 sc0 ls1 ws29d">FIG<span class="_e blank"> </span>2. <span class="ff3f ws297">Reduced<span class="_e blank"> </span>allerge nicity<span class="_15 blank"> </span>of<span class="_e blank"> </span>melon<span class="_e blank"> </span>allergens<span class="_15 blank"> </span>after<span class="_e blank"> </span>incubation<span class="_15 blank"> </span>with</span></div><div class="t m4f x87 ha8 y32e ff3f fs7e fc0 sc0 ls1 ws29e">gastric enzymes. After subjection<span class="_10 blank"> </span>to SGF, melon allerge<span class="_1 blank"> </span>ns induce a smaller</div><div class="t m4f x87 ha8 y32f ff3f fs7e fc0 sc0 ls1 ws29f">wheal reaction in a patient with melon<span class="_17 blank"> </span>allergy<span class="_17 blank"> </span>compared with<span class="_17 blank"> </span>the undi-</div><div class="t m4f x87 ha8 y330 ff3f fs7e fc0 sc0 ls1 ws2a0">gested<span class="_18 blank"> </span>extract.<span class="_18 blank"> </span>The<span class="_18 blank"> </span>alteration<span class="_18 blank"> </span>of<span class="_18 blank"> </span>skin<span class="_18 blank"> </span>reactivity<span class="_18 blank"> </span>was<span class="_a blank"> </span>dependen t<span class="_18 blank"> </span>on<span class="_18 blank"> </span>the</div><div class="t m4f x87 ha8 y331 ff3f fs7e fc0 sc0 ls1 ws2a1">incubation<span class="_f blank"> </span>time<span class="_f blank"> </span>with<span class="_f blank"> </span>the<span class="_f blank"> </span>proteolytic<span class="_10 blank"> </span>enzymes .</div><div class="t m4f x99 ha9 y332 ff3e fs7f fc0 sc0 ls1 ws2a2">TABLE II. <span class="ff3f ws2a3">Key concepts and<span class="_9 blank"> </span>safety implications</span></div><div class="t m4f x99 haa y333 ff3c fs7f fc0 sc0 ls1 ws2a4">Regulatory authorities might consider a re-evaluation of currently applied</div><div class="t m4f xe7 haa y334 ff3c fs7f fc0 sc0 ls1 ws2a5">safety tests for novel (eg, genetically modi\ufb01<span class="_0 blank"></span>ed) food compounds.</div><div class="t m4f x99 haa y335 ff3c fs7f fc0 sc0 ls1 ws2a6">Patients should be advised that<span class="_9 blank"> </span>threshold levels might vary in situations of</div><div class="t m4f xe7 haa y336 ff3c fs7f fc0 sc0 ls1 ws2a7">altered protein digestion. This problem also af<span class="_0 blank"></span>fects current ef<span class="_0 blank"></span>forts to</div><div class="t m4f xe7 haa y337 ff3c fs7f fc0 sc0 ls1 ws2a8">de\ufb01ne no-observ<span class="_0 blank"></span>ed-adverse-ef<span class="_0 blank"></span>fect lev<span class="_0 blank"></span>els for food allergens.</div><div class="t m4f x99 haa y338 ff3c fs7f fc0 sc0 ls1 ws2a9">Dietary recommendations and repeated allergologic testing of long-term</div><div class="t m4f xe7 haa y339 ff3c fs7f fc0 sc0 ls1 ws2a8">acid-suppressed patients could prev<span class="_0 blank"></span>ent unexpected allerg<span class="_0 blank"></span>ic reactions on</div><div class="t m4f xe7 haa y33a ff3c fs7f fc0 sc0 ls1 ws2aa">food ingestion.</div><div class="t m4f x87 hab y33b ff3f fs80 fc0 sc0 ls1 ws2ab">J ALLERGY CLIN IMMUNOL</div><div class="t m4f x87 hab y33c ff3f fs80 fc0 sc0 ls1 ws2ac">VOLUME 121, NUMBER 6</div><div class="t m4f xbe ha9 y33b ff3f fs7f fc0 sc0 ls1 ws2ad">UNTERSMAYR AND JENSEN-JAROLIM<span class="_18 blank"> </span><span class="ff3e">1305</span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div> <div id="pfa" class="pf w0 h0" data-page-no="a"><div class="pc pca w0 h0"><img fetchpriority="low" loading="lazy" class="bi x0 y0 w1 h1" alt="" src="https://files.passeidireto.com/d59e71cd-dd8e-428a-9f27-ea603d8b4243/bga.png"><div class="c x0 y1 w1 h1"><div class="t m0 xe8 h2 y2 ff1 fs0 fc0 sc0 ls9f">10</div><div class="t m0 x2 h2 y3 ff1 fs0 fc0 sc0 ls2 wsb">Fundame<span class="_0 blank"></span>ntos<span class="_0 blank"></span> de Nutriçã<span class="_0 blank"></span>o <span class="ls3">e <span class="ls4 ws0">Metaboli<span class="_1 blank"> </span>smo</span></span></div><div class="t m0 x2 h2 y4 ff1 fs0 fc0 sc0 ls5 wsb">Pedro <span class="ls6 ws1">Carrera </span><span class="ls7">Bastos, 2016</span></div><div class="t m0 x2 h3 y5 ff2 fs0 fc0 sc0 ls8 ws2">Nutr<span class="_1 blank"> </span>iSci<span class="_1 blank"> </span>ence <span class="ls9 wsb">| <span class="lsa ws3">We l l<span class="_1 blank"> </span>X P r o S c h o o<span class="_1 blank"> </span>l<span class="_2 blank"> </span><span class="lsb ws4">www<span class="_3 blank"></span>.nutriscience.pt</span></span></span></div></div><div class="c x3 y6 w2 h4"><div class="t m1 x27 h10 yd2 ff2 fsc fc7 sc0 ls1e wse0">Untersmayr <span class="ls1f wsb">E, <span class="ls72 wse1">Jensen<span class="ls1 ws2e">-</span><span class="wse2">Jarolim </span></span>E. <span class="ls72 wsdc">Journa<span class="_0 blank"></span>l <span class="ls22 wsdd">of <span class="ls21 wse3">Allergy <span class="ls25 ws20">and <span class="ls1e wsda">Clinical <span class="ls26 wsb">Immunology. 2008 Jun;121(6):1301<span class="ls1 ws2e">\u2013</span><span class="ls25">8. </span></span></span></span></span></span></span></span></div><div class="t m1 x14 hac y33d ff1 fs8 fc7 sc0 ls55 wsb">Máxima actividade <span class="ls1b">proteolítica da Pepsina: </span></div><div class="t m1 x71 h21 y33e ff4 fs6 fc7 sc0 lsa0 wsb">pH entre 1,8 e 3,2</div></div><div class="c x3 yc w2 h4"><div class="t m1 xe had y33f ff5 fs14 fc7 sc0 lsa1 ws2ae">Intestino <span class="ff25 fc0 ls92 wsb v4">Pool <span class="_3 blank"></span>Aa </span></div><div class="t m1 x63 hae y340 ff25 fs14 fc0 sc0 ls1 ws2af">livres</div><div class="t m1 xe9 haf y341 ff5 fs14 fc0 sc0 ls92 wsb">Proteína </div><div class="t m1 xe9 haf y342 ff5 fs14 fc0 sc0 lsa2 ws2b0">tecidual</div><div class="t m1 x2e hae y343 ff25 fs14 fc0 sc0 ls1 ws2af">Síntese</div><div class="t m1 x2e hae y344 ff25 fs14 fc0 sc0 ls1 ws2af">Proteica</div><div class="t m1 xea hae y345 ff25 fs14 fc0 sc0 ls1 wsb">Fezes </div><div class="t m1 x3d hae y346 ff25 fs14 fc0 sc0 ls1 wsb">Dieta \u2192 PRO/Aa</div><div class="t m1 x5a hae y347 ff25 fs14 fc0 sc0 ls1 ws2af">Absorção</div><div class="t m1 xeb h10 y348 ff2 fsc fc3 sc0 ls21 wsab">Adaptado <span class="ls2f wsb">de [Lemon PW. <span class="ls26">Int J Sport <span class="ls1e ws21">Nutr</span>. 1998 Dec;8(4):426<span class="ls1 ws2e">-<span class="ls25 ws2b1">47</span></span><span class="ls53">] </span></span><span class="ws1f">por <span class="ls23 ws2b2">Rogero </span></span><span class="ls50">MM, 201<span class="_0 blank"></span>4.</span></span></div></div></div><div class="pi" data-data='{"ctm":[1.000000,0.000000,0.000000,1.000000,0.000000,0.000000]}'></div></div>
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