Nitric oxide synthase-catalyzed activation of oxygen and reduction of cytochromes: reaction mechanisms and possible physiological implications.
Purified cerebellar nitric oxide (NO) synthase was found to reduce molecular oxygen to hydrogen peroxide at low concentrations of its substrate L-arginine or its cofactor tetrahydrobiopterin. The characteristics of oxygen reduction appeared to be similar to NO synthesis, as both reactions required reduced nicotinamide adenine dinucleotide phosphate (NADPH), were dependent on Ca2+/calmodulin, and showed optimal reaction rates at slightly acidic conditions. The electron transport from NADPH to molecular oxygen is probably mediated by the reduced flavins, flavine adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are bound in stoichiometrical amounts to the enzyme. NO synthase shows similarities to cytochrome P450 (cytochrome c) reductase, another FAD- and FMN-containing enzyme, and we found that NO synthase reduced cytochromes and artificial, low molecular mass electron acceptors in a superoxide dismutase-insensitive manner. Thus, NO synthase apparently represents a Ca(2+)-regulated, soluble isoform of cytochrome P450 reductase.
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport; D005486:Flavin Mononucleotide / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D019001:Nitric Oxide Synthase; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*
D003574:Cytochrome c Group; D005182:Flavin-Adenine Dinucleotide; D001708:Biopterins; D009249:NADP; D005486:Flavin Mononucleotide; D001120:Arginine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009245:NADH Dehydrogenase; C003402:sapropterin; D010100:Oxygen