AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 5 699-L722, Copyright © 1995 by American Physiological Society
The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide
W. A. Pryor and G. L. Squadrito
Biodynamics Institute, Louisiana State University, Baton Rouge 70803, USA.
Nitric oxide and superoxide, which are produced by several cell types,
rapidly combine to form peroxynitrite. This reaction can result in nitric
oxide scavenging, and thus mitigation of the biological effects of
superoxide. Also, superoxide can trap and hence modulate the effects of
nitric oxide; superoxide dismutase, by controlling superoxide levels,
therefore can influence the reaction pathways open to nitric oxide. The
production of peroxynitrite, however, causes its own sequelae of events:
Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a
potent and versatile oxidant that can attack a wide range of biological
targets. The peroxynitrite anion is relatively stable, but its acid,
peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of
approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann
distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity
constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve
two-electron processes (such as an SN2 displacement) or a one-electron
transfer (ET) reaction in which the substrate is oxidized by one electron
and peroxynitrite is reduced. These oxidation reactions could involve one
of two mechanisms. The first mechanism is homolysis of HOONO to give HO.
and .NO2, which initially are held together in a solvent cage. This caged
pair of radicals (the "geminate" pair) can either diffuse apart, giving
free radicals that can perform oxidations, or react together either to form
nitrate or to reform HOONO (a process called cage return). A large amount
of cage return can explain the small entropy of activation (Arrhenius
A-factor) observed for the decomposition of HOONO. A cage mechanism also
can explain the residual yield of nitrate that appears to be formed even in
the presence of high concentrations of all of the scavengers studied to
date, since scavengers capture only free HO. and .NO2 and not caged
radicals. If the cage mechanism is correct, the rate of disappearance of
peroxynitrite be slower in solvents of higher viscosity, and we do not find
this to be the case. The second mechanism is that an activated isomer of
peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO*
mechanism can explain the inability of hydroxyl radical scavengers to
completely block either nitrate formation or the oxidation of substrates
such as methionine, since HOONO* would be less reactive, and therefore more
selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400
WORDS)
