Nitroxyl oxidizes NADPH in a superoxide dismutase inhibitable manner.
Nitric oxide synthases (NOS) convert L-arginine and N(omega)-hydroxy-L-arginine to nitric oxide (*NO) and/or nitroxyl (NO(-)) in a NADPH-dependent fashion. Subsequently, *NO/superoxide (O(2-)-derived peroxynitrite (ONOO(-)) consumes one additional mol NADPH. The related stoichiometry of NO(-) and NADPH is unclear. We here describe that NO(-) also oxidizes NADPH in a concentration-dependent manner. In the presence of superoxide dismutase (SOD), which also converts NO(-) to *NO, nitrite accumulation was almost doubled and no oxidation of NADPH was observed. Nitrate yield from NO(-) was low, arguing 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.
Reif
A
A
Clinical Neurochemistry, Department of Psychiatry and Psychotherapy, Julius-Maximilians-University, Würzburg, Germany. a.reif@gmx.net
Zecca
L
L
Riederer
P
P
Feelisch
M
M
Schmidt
H H
HH
D005609:Free Radicals; D009249:NADP / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism*
D005609:Free Radicals; D009589:Nitrogen Oxides; D016877:Oxidants; D009249:NADP; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; C039900:nitroxyl