Diffusion and Transport of Peroxynitrite across Cell Membranes

Abstract

Peroxynitrite (ONOO−/ONOOH) is a strong oxidant formed in vivo. It is cytotoxic at high concentrations, participates in different diseases and the aging process, and contributes to immune cell response mechanisms to invading organisms. The mechanism of action of peroxynitrite in these processes depends on the oxidation of biomolecules either by direct reaction or by the reaction of derived secondary species. This review presents the biological chemistry of peroxynitrite and the derived radicals nitrogen dioxide, hydroxyl radical and carbonate radical, particularly discussing their diffusion properties across cellular membranes and in the context of their short biological half-lives. While in some cases simple diffusion is the main route, peroxynitrite can also use anion channels to traverse cellular membranes. Furthermore, the potential role of aquaporins in facilitating the diffusion of peroxynitrite and its neutral conjugate acid is discussed. The wide range of membrane permeabilities exhibited by precursors, peroxynitrite and its secondary radical species results in an unequal compartmentalization of peroxynitrite formation and reactions and decay, thus partially defining the biological sites of action of peroxynitrite.