AQUEOUS NITRIC OXIDE AUTOXIDATION: EVIDENCE AGAINST TI-tE PRODUCTION OF NITROGEN DIOXIDE

Nitric oxide (NO) oxidation occurs spontaneously in aerobic environments and potentiates the detrimental effects of NO production in the body. This autoxidation reaction can form reactive nitrogen oxygen species, capable of oxidizing and nitrosating proteins, lipids, and DNA, potentially leading to tissue damage, disease, and cancer. Autoxidation of NO in the gas phase is well-characterized, and produces such intermediates, particularly nitrogen dioxide (NO2 ) and dinitrogen trioxide (N2O3 ). The mechanism of NO autoxidation in aqueous media has commonly been assumed to be analogous to the gas phase reaction, with the extension of N2O3 hydrolysis to form nitrite. We propose that NO autoxidation within cells occurs through a mechanism that is fundamentally different from the gas phase reaction, producing variants of the above intermediates that possess distinct nitrosative and oxidative capabilities. Although the rate constant for aqueous NO autoxidation has been determined to be similar to the gas phase reaction, results support a unique mechanism. Using competitive kinetics techniques, new insight into the mechanism of NO autoxidation has been achieved. The characterization of aqueous phase NO autoxidation is thus critical to fully understanding the pathophysiology of NO in biological systems.