Nitroxyl oxidizes NADPH in a superoxide dismutase inhibitable manner

Nitric oxide synthases (NOS) convert L-arginine and N-omega-hydroxy-L-argin ine to nitric oxide ((NO)-N-.) and/or nitroxyl (NO-) in a NADPH-dependent f ashion. Subsequently, (NO)-N-./superoxide (O-2(-)-derived peroxynitrite (ON OO-) consumes one additional mol NADPH. The related stoichiometry of NO- an d NADPH is unclear. We here describe that NO- also oxidizes NADPH in a conc entration-dependent manner. In the presence of superoxide dismutase (SOD), which also converts NO- to (NO)-N-., nitrite accumulation was almost double d and no oxidation of NADPH was observed. Nitrate yield from NO- was low, a rguing against intermediate ONOO- formation. Thus, biologically formed NO- may function as an effective pro-oxidant unless scavenged by SOD and affect the apparent NADPH stoichiometry of the NOS reaction. (C) 2001 Elsevier Sc ience Inc.