IUBMB Enzyme Nomenclature

EC 1.14.13.39

Accepted name: nitric-oxide synthase (NADPH dependent)

Reaction: 2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O (overall reaction)
(1a) 2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nω-hydroxy-L-arginine + 2 NADP+ + 2 H2O
(1b) 2 Nω-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O

Other name(s): nitric oxide synthetase; endothelium-derived relaxation factor-forming enzyme; endothelium-derived relaxing factor synthase; NO synthase; NADPH-diaphorase

Systematic name: L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)

Comments: Binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin. This eukaryotic enzyme, which is found in plants [4] and animals [1-3], consists of oxygenase and reductase domains that are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. May produce superoxide under certain conditions [3]. cf. EC 1.14.13.165, nitric-oxide synthase [NAD(P)H dependent].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 125978-95-2

References:

1. Bredt, D.S. and Snyder, S.H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. USA 87 (1990) 682-685. [PMID: 1689048]

2. Stuehr, D.J., Kwon, N.S., Nathan, C.F., Griffith, O.W., Feldman, P.L. and Wiseman, J. Nω-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J. Biol. Chem. 266 (1991) 6259-6263. [PMID: 1706713]

3. Stuehr, D., Pou, S. and Rosen, G.M. Oxygen reduction by nitric-oxide synthases. J. Biol. Chem. 276 (2001) 14533-14536. [PMID: 11279231]

4. Foresi, N., Correa-Aragunde, N., Parisi, G., Calo, G., Salerno, G. and Lamattina, L. Characterization of a nitric oxide synthase from the plant kingdom: NO generation from the green alga Ostreococcus tauri is light irradiance and growth phase dependent. Plant Cell 22 (2010) 3816-3830. [PMID: 21119059]

[EC 1.14.13.39 created 1992, modified 2012]


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