Permeation of phospholipid membranes by peroxynitrite

Quantitative kinetic models have been developed for the reaction between peroxynitrite and membrane lipids in vesicles and for transmembrane oxidation of reactants located within their inner aqueous cores. The models were used to analyze TBARS formation and oxidation of entrapped Fe(CN)(6)(4)(-) ion in egg lecithin liposomes and several artificial vesicles. The analyses indicate that permeation of the bilayers by ONOOH and NO(2)(*), a radical formed by homolysis of the ONOOH bond, is unusually rapid but that permeation by ONOO(-) and CO(3)(*)(-), a radical formed when CO(2) is present, is negligible. Bicarbonate protects the vesicles against both membrane and Fe(CN)(6)(4)(-) oxidation by rapid competitive CO(2)-catalyzed isomerization of ONOOH to NO(3)(-); this effect is partially reversed by addition of nitrite ion, which reacts with CO(3)(*)(-) to generate additional NO(2)(*). Under medium conditions mimicking the physiological milieu, a significant fraction of the oxidants escape to inflict damage upon the vesicular assemblies. Rate constants for several elementary reaction steps, including transmembrane diffusion rates for ONOOH and NO(2)(*), were estimated from the bicarbonate dependence of the oxidative reactions.