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 is obutyl. nitrites to nitric oxide (NO) in the presence of xanthine under ana erobic conditions. NO was produced at a stoichiometric ratio of 2:1 versus urate generation, steady-state analysis of which showed Michaelis-Menten ki netics with xanthine as varied substrate and substrate inhibition with vari ed organic nitrite. Under the conditions of NO generation from isoamyl nitr ite, XO was progressively inactivated by a mechanism involving conversion o f Mo=S to Mo=O, yielding "desulfo" enzyme. It is proposed that XO is involv ed in the metabolism of organic nit rites to NO in vivo and that the observ ed inactivation serves to explain the phenomenon of tolerance. (C) 2000 Aca demic Press.