I'm Raphael Radi from
the Department of Biochemistry and Center for
Free Radical and Biomedical Research of the School of Medicine,
Universidad de la Republica in Montevideo, Uruguay.
Today, I will presenting you with peroxynitrite biochemistry,
oxidation and nitration reaction.
Our first contribution to the field was published
in the Journal of Biological Chemistry in 1991.
While I was working at the University of Alabama at
Birmingham with Joe Beckman and Bruce Freeman,
we found that the product of
the reaction between superoxide and nitric oxide peroxynitrite,
was capable of rapidly oxidizing sulfhydryl groups.
In this paper, in the figure 9,
we propose an alternative mechanism to
the current concepts on superoxide-mediated oxidative damage.
Indeed, in those days,
the mechanism proposed for superoxide mediated for radical dependent damage
involved the dismutation of superoxide by
the superoxide dismutases through hydrogen peroxide,
followed by the ferrous iron-dependent reduction of
H2O2 to the highly oxidizing hydroxyl radical in the so-called phantom reaction.
The alternative mechanism proposed by ourselves during those days was that superoxide,
instead of dismutating could alternatively react with nitric oxide to yield
a secondary species called peroxynitrite anion in equilibrium with peroxynitrous acid,
which could either promote thiol oxidation or evolve via
homolysis of the oxygen-oxygen bond on
peroxynitrous acid to hydroxyl radical and nitrogen dioxide radical.
This was an alternative mechanism of superoxide-mediated cytotoxicity that
not only explain how superoxide can evolve into a stronger oxidant,
but also how superoxide could modulate
the very availability of nitric oxide
while at the same time producing a stronger oxidant.