The versatile and complex enzymology of nitric oxide synthase.
The biogenesis of nitric oxide is catalyzed by nitric oxide synthase (NOS) which forms L-citrulline and NO from L-arginine. Here we review the enzymology of NOS. We discuss its modular structure, its prosthetic groups and cofactors, and we provide a brief account of present knowledge regarding cellular targeting and regulation of the different isoforms. The various reactions which are catalyzed by NOS are reviewed, and an inventory of different inhibitor types is given. Special attention is paid to the role of the cofactor tetrahydrobiopterin (BH4) and of the dimeric structure, and to the possibility that the main product of NOS catalysis under some conditions may not be NO. Based on a number of recent observations, we postulate that neuronal NOS with one equivalent of BH4 per dimer (a state which may be physiologically relevant) catalyzes the concerted formation of peroxynitrite.
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010, Graz, Austria. antonius.gorren@kfunigraz.ac.at
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D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D011487:Protein Conformation
D009566:Nitrates; D001708:Biopterins; C039642:peroxynitric acid; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin; D002118:Calcium