Chapter 4 - The Biological Chemistry of Peroxynitrite

Abstract

This chapter provides a comprehensive overview of the physical and biological chemistry of peroxynitrite. A foundation is provided to rationalize the biological fate and actions of peroxynitrite and the strategies for preventing peroxynitrite-dependent biological damage and pathology. Peroxynitrite anion is formed in vivo as a result of the diffusion controlled reaction between nitric oxide (NO) and superoxide anion radicals. The anion and its conjugated acid, peroxynitrous acid, are strong oxidant species that cause molecular damage in a variety of pathophysiological conditions. Peroxynitrite reacts fast with a number of biological targets, including thiols, metalloproteins, and carbon dioxide, or more slowly decomposes to hydroxyl and nitrogen dioxide radicals by proton-catalyzed homolysis. Carbon dioxide accounts for a significant fraction of peroxynitrite consumption and leads to the secondary formation of carbonate and nitrogen dioxide radicals. At the molecular level, the predominant outcome of peroxynitrite reactions in vivo is one or two electron oxidations and nitrations. Peroxynitrite can diffuse through tissue compartments, being able to cross biomembranes by both passive diffusion and anion channels. Thus, although the biological half-life of peroxynitrite is short, it is sufficient for peroxynitrite to diffuse a couple of cell diameters and cause biological effects distant from its site of production.