Hemoglobin myoglobin

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Myoglobin & Hemoglobin
Structure & Function of Biomolecules
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Oxygen Transport Proteins
Myoglobin
Exhibits Michaelis-Menten properties
Hemoglobin
Exhibits allosteric properties
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Myoglobin
Single polypeptide
16,700 daltons
8 a helices (A-H) 
Located in skeletal & cardiac muscle
[high] in diving mammals like whale & seals
http://www.agen.ufl.edu/~chyn/age2062/lect/lect_02/3_27.gif
Heme prosthetic group
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Heme Prosthetic Group
Heme (Fe2+) has affinity for O2.
Hematin (Fe3+) cannot bind O2.
Located in crevice where it is protected from oxidation.
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Oxygen Binding to Myoglobin
O2 binds to only available coordination site on iron atom.
His 93 (proximal his) binds directly to iron.
His 64 (distal his) stabilizes the O2 binding site.
http://cwx.prenhall.com/horton/medialib/media_portfolio/text_images/FG04_44.JPG
distal histidine
proximal histidine
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O2 Binding Curve
Myoglobin has high affinity for O2.
P50 = 2.8 Torr
Allows myoglobin to act as O2 storage reserve.
Releases O2 when pO2 becomes low indicating O2 deprivation.
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Hemoglobin
Heterotetramer
HbA (most common)
a2b2
2 dimers
a1b1 and a2b2
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Hemoglobin Structure
Each polypeptide chain resembles myoglobin tertiary structure but 1˚ sequence varies.
Invariant residues indicate importance of those residues in function.
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Oxygen Binding
(R state)
(T state)
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Bohr Effect
 CO2 pH
Some side groups remain protonated at lower pH.
Stabilizes T state and promotes unloading of O2 to active tissues.
Binding of CO2 also stabilizes T state.
CO2 binds to a amino groups. 
http://cwx.prenhall.com/horton/medialib/media_portfolio/text_images/FG04_50.JPG
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2, 3-Bisphosphoglycerate
Stabilizes deoxyHb (T state)
Facilitates unloading of O2 in tissue.
pO2 (partial pressure of O2) (Torr)
20
100
saturation with O2
100
50
- BPG
+ BPG
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2,3-BPG Binding to Hb
http://oregonstate.edu/instruction/bb450/stryer/ch10/Slide26.jpg
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High Altitude and BPG
At higher altitudes, the [BPG] increases allowing Hb to unload O2 more easily.
http://www.bio.davidson.edu/Courses/anphys/1999/Yusi/dpgoxyhbgraph.jpg
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Stored Blood & BPG
2,3-BPG becomes depleted in stored blood, so R state of Hb is stabilized.
If BPG depleted blood is used for a transfusion, the R state Hb doesn’t release O2.
Add inosine to stored blood to maintain BPG levels.
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CO Poisoining
CO is “competitive inhibitor” of O2.
Affinity is 200X greater than that of O2.
 CO also inhibits unloading O2 of in tissues.