Ll. Pearce et al., The peroxynitrite reductase activity of cytochrome c oxidase involves a two-electron redox reaction at the heme a(3)-Cu-B site, J BIOL CHEM, 274(50), 1999, pp. 35763-35767
Fully and partially reduced forms of isolated bovine cytochrome c oxidase u
ndergo a two-electron oxidation-reduction process with added peroxynitrite,
leading to catalytic oxidation of ferrocytochrome c to ferricytochrome c,
The other major reaction product is nitrite ion, 86% of the added peroxynit
rite being measurably converted to this species. The reaction is inhibited
in the presence of cyanide, implicating the heme alpha(3)-Cu-B binuclear pa
ir as the active site. Moreover, provided peroxynitrite is not added to exc
ess, the reductase activity of the enzyme toward this oxidant efficiently p
rotects other protein and detergent molecules in vitro from nitration of ty
rosine residues and oxidative damage. If the enzyme is exposed to similar t
o 10(2)-fold excesses of peroxynitrite, then significant irreversible loss
of electron transfer activity results, and the heme alpha(3)-Cu-B binuclear
pair no longer undergo a characteristic carbon monoxide-driven reduction.
The accompanying rather small changes in the observed electronic absorption
spectrum are suggestive of a modification in the vicinity of one or both h
emes but probably not to the cofactors themselves.