An ab initio study of an oxidative mechanism that forms nitric oxide from theN-hydroxyguanidinium ion

The free-radical nitric oxide is now considered to play an important role in mammalian physiology and pathology. Enzymatic studies have shown that nitric oxide biosynthesis is initiated by an NADPH-dependentN-hydroxlation ofl-arginine, formingN -hydroxy-l-arginine as an intermediate. However, the subsequent enzymatic steps that generate nitric oxide fromN -hydroxy-l-arginine are unknown. We have used ab initio quantum chemical calculations to investigate a mechanism that forms nitric oxide fromN-hydroxyguanidine, used as a model forN -hydroxy-l-arginine. Our calculations indicate that mechanisms of nitric oxide formation involving nucleophilic attack by hydroperoxy anion at theN-hydroxyguanidine carbon are energetically feasible.