Peroxynitrite biochemistry oxidation and nitration reactions

Published on September 27, 2018   42 min

Other Talks in the Therapeutic Area: Cardiovascular & Metabolic

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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.
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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.
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Peroxynitrite biochemistry oxidation and nitration reactions

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