Living in an Oxygen Atmosphere – NO• Problem?

Abstract

Formation of nitrogen monoxide in vivo as a signal molecule and as part of the immunological response leads to the formation of oxidized haemoproteins and a powerful oxidant, peroxynitrite. The latter is an unstable isomer of nitrate that, in the protonated form, oxidizes and nitrates biomolecules. Peroxynitrite is formed from the diffusion-controlled reaction of superoxide with nitrogen monoxide. The hypothesis that peroxynitrous acid undergoes homolysis to nitrogen dioxide and hydroxyl radicals is not substantiated by analyses of the products of peroxynitrite decay. Peroxynitrite has been stabilized as a ligand of cobalt(III). Nitrogen monoxide reacts very rapidly with oxyhaemoglobin and oxymyoglobin to generate intermediate iron(III)peroxynitrito complexes that do not nitrate the tyrosine residues in the globin. Peroxynitrite oxidizes oxymyoglobin to the iron(III) form of the protein via the high valent oxoiron(iv)myoglobin. The two tyrosine residues of myoglobin are nitrated in only very low yield. Peroxynitrite can be efficiently scavenged by an iron(III)myoglobin mutant in which the distal histidine has been replaced with an alanine. We propose that the reactions of myoglobin with nitrogen monoxide and peroxynitrite may be essential to preserve respiration in the skeletal muscle.