Reductive Release of Nitric Oxide from Nitrosothiols

Reductive Release of Nitric Oxide from Nitrosothiols 

Nitrosothiols such as cysteine-NO, glutathione-NO, and S-nitroso-N-acetylpenicillamine (SNAP) are often used a nitric oxide donors. The biological effects of these compounds suggest that they do, in fact, release significant amounts of nitric oxide, but the mechanism of release is not at 

The reaction of nitric oxide with thiyl radicals may be a significant route of forming nitrosothiols in vivo. Alternatively it is easy to write a balanced reaction in which 2 mol of nitrosothiol react with each other to form a disulfide, thereby releasing 2 mol of nitric oxide. 

The reduced form of a transition metal could also catalyze nitric oxide release by providing the needed electron. 

Additional experiments in our laboratory utilizing a superoxidegenerating system support the reductive release of nitric oxide. Under conditions in which no nitric oxide could be detected from SNAP, the addition of xanthine oxidase plus pterin as substrate resulted in a sustained linear oxidation of dihydrorhodamine that was inhibitable by SOD (Crow and Beckman, unpublished observations). We have shown previously that dihydrorhodamine is oxidized by ONOO but not by nitric oxide or superoxide (Kooy et al., 1994). These results are consistent with the reaction scheme shown below, whereby the first superoxide reduces the nitrosothiol, resulting in nitric oxide release, which in turn, reacts with a second superoxide to produce ONOO.  

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D. Reductive Release of Nitric Oxide from Nitrosothiols... 

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