Peroxynitrite physiological importance

It has now been more than a decade since Beckman and his collaborators first disclosed their observations that the combination of two relatively unreactive, yet biologically relevant free radicals, superoxide anion and nitric oxide, would produce a new highly reactive physiologically important reagent. The interaction of these two presumably innocuous species appears to be diffusion controlled and produces a thermally stable peroxy anion, peroxynitrite (equation 1). ... 

In contrast to the findings obtained in Ref. [34], it was concluded [36,37] that exposure of proteins to peroxynitrite leads to a very small increase in carbonyl content at physiological pH and C02 concentration. At the same time, carbonyl contents in glutamine synthetase and BSA increased in the absence of C02. These data show the importance of C02 in the... 

An important physiological reaction of nitric oxide (NO) is its interaction with the superoxide ion (O2-) to form the peroxynitrite ion (ONOO-). 

In the same study (34), the reaction of MnSOD with NO imder aerobic (and thus more physiological) conditions was also studied, and the second-order rate constant for the reaction of MnSOD (E. coli) with NO under aerobic conditions was determined to be 650M s. It should be mentioned that this rate constant is not the catalytic rate constant for NO removal by MnSOD, since the experimental conditions used in the study were not catalytic. Further, it is possible that this constant is largely underestimated because of the relatively slow response time of the NO electrode used in the study to follow the reaction. However, the authors demonstrate that dismutation indeed takes place and that even reduction of NO, considered to be thermodynamically impossible (vide infra), is possible. More importantly, they propose that this reaction could present a defense mechanism against overproduction of NO and its subsequent toxic effects due to the reaction with superoxide and peroxynitrite formation. These two reactions of MnSOD, one with NO and the other with ONOOH, stimulated further studies on SOD mimics with RNS and showed that none of them in fact posses strict selectivity toward superoxide. 

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