Reduction of organic nitrites to nitric oxide catalyzed by xanthine oxidase: Possible role in metabolism of nitrovasodilators

Xanthine oxidase (XO) was shown to catalyze the reduction of isoamyl and isobutyl. nitrites to nitric oxide (NO) in the presence of xanthine under anaerobic conditions. NO was produced at a stoichiometric ratio of 2:1 versus urate generation, steady-state analysis of which showed Michaelis-Menten kinetics with xanthine as varied substrate and substrate inhibition with varied organic nitrite. Under the conditions of NO generation from isoamyl nitrite, XO was progressively inactivated by a mechanism involving conversion of Mo=S to Mo=O, yielding "desulfo" enzyme. It is proposed that XO is involved in the metabolism of organic nit rites to NO in vivo and that the observed inactivation serves to explain the phenomenon of tolerance. (C) 2000 Academic Press.