Espécies Reativas de Oxigênio e Estresse Oxidativo

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Espécies Reativas de Oxigênio (EROs)
Redução incompleta do O2 ! Diferente da atividade do complexo IV !
Sítios da CTE de geração de espécies reativas de O2
Outros sítios mitocondriais de geração de EROs
Fisiologicamente, EROs são importantes
Mas, se não controlados ou se produzidos em excesso, são danosos
Balanço das EROs e defesas antioxidantes 
Superóxido dismutase
Catalase
Glutationa peroxidase
Balanço das EROs e defesas antioxidantes 
Sinalização REDOX
Sinalização REDOX
Sinalização REDOX
Mecanismos de estresse oxidativo
Peroxidação de lipídios de membranas
Oxidação de DNA
Mecanismos de estresse oxidativo
Mecanismos de estresse oxidativo
Carbonilação de proteínas
one protein (cytochrome c) playing two very different
roles in the cell.
Mitochondria are also involved in the cell’s response
to oxidative stress. As we have seen, several steps in
the path of oxygen reduction in mitochondria have the
potential to produce highly reactive free radicals that
can damage cells. The passage of electrons from QH2 to
cytochrome bL through Complex III, and passage of elec-
trons from Complex I to QH2, involve the radical !Q" as
an intermediate. The !Q" can, with a low probability,
pass an electron to O2 in the reaction
O2 # e" On !O2"
The superoxide free radical thus generated, !O2", is very
reactive and can damage enzymes, membrane lipids,
and nucleic acids. Antimycin A, an inhibitor of Complex
III, may act by occupying the QN site (Fig. 19–11), thus
blocking the Q cycle and prolonging the binding of !Q"
to the QP site; this would increase the likelihood of su-
peroxide radical formation and cellular damage. From
0.1% to as much as 4% of the O2 used by actively respir-
ing mitochondria forms !O2"—more than enough to have
lethal effects on a cell unless the free radical is quickly
disposed of. 
To prevent oxidative damage by !O2", cells have sev-
eral forms of the enzyme superoxide dismutase,
which catalyzes the reaction
2 !O2" # 2H# 88n H2O2 # O2
The hydrogen peroxide (H2O2) generated by this reac-
tion is rendered harmless by the action of glutathione
peroxidase (Fig. 19–35). This enzyme is remarkable for
the presence of a selenocysteine residue (see Fig. 3–8a),
in which an atom of selenium replaces the sulfur atom
normally present in the thiol of the side chain. The se-
lenol group (OSeH) is more acidic than the thiol (OSH);
its pKa is about 5, so at neutral pH, the selenocysteine
side chain is essentially fully ionized (OCH2Se"). Gluta-
thione reductase recycles oxidized glutathione to its re-
duced form, using electrons from the NADPH formed
by nicotinamide nucleotide transhydrogenase or by the
pentose phosphate pathway (see Fig. 14–20). Reduced
glutathione also serves in keeping protein sulfhydryl
groups in their reduced state, preventing some of the
deleterious effects of oxidative stress (Fig. 19–35).
SUMMARY 19.5 The Role of Mitochondria in
Apoptosis and Oxidative Stress
! Mitochondrial cytochrome c, released into the
cytosol, participates in activation of one of the
proteases (caspase 9) involved in apoptosis.
! Reactive oxygen species produced in
mitochondria are inactivated by a set of
protective enzymes, including superoxide
dismutase and glutathione peroxidase.
Chapter 19 Oxidative Phosphorylation and Photophosphorylation722
Nicotinamide
nucleotide
transhydrogenase
NADH
NADPH
GSSG
H2O2
H2O
2 GSH
S
S
2 GSHEnz
inactive
active
oxidative
stress
protein thiol
reduction
GSSG
NADP+
glutathione
reductase
glutathione
peroxidase
superoxide
dismutaseNAD+
O2 O2
NAD+
Inner
mitochondrial
membrane
Q III
IV
I
Cyt c
. –
SH
SH
FIGURE 19–35 Mitochondrial production and disposal of super-
oxide. Superoxide radical, ?O2", is formed in side reactions at
Complexes I and III, as the partially reduced ubiquinone radical (?Q")
donates an electron to O2. The reactions shown in blue defend the
cell against the damaging effects of superoxide. Reduced glutathione
(GSH; see Fig. 22–27) donates electrons for the reduction of hydrogen
peroxide (H2O2) and of oxidized Cys residues (OSOSO) in proteins,
and GSH is regenerated from the oxidized form (GSSG) by reduction
with NADPH. 
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