nitric-oxide synthase (NADPH dependent);
nitric oxide synthetase;
endothelium-derived relaxation factor-forming enzyme;
endothelium-derived relaxing factor synthase;
NO synthase;
NADPH-diaphorase

Oxidoreductases;
Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor

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

2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O (overall reaction) [RN:R00557];
(1a) 2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O  [RN:R00558];
(1b) 2 Nomega-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O [RN:R00111]

R00111 R00557 R00558

L-arginine [CPD:C00062];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007];
Nomega-hydroxy-L-arginine

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].

1  [PMID:1689048]

Bredt DS, Snyder SH.

Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.

Proc. Natl. Acad. Sci. U. S. A. 87 (1990) 682-5.

Rattus norvegicus [GN:rno]

2  [PMID:1706713]

Stuehr DJ, Kwon NS, Nathan CF, Griffith OW, Feldman PL, Wiseman J

N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine.

J. Biol. Chem. 266 (1991) 6259-63.

3  [PMID:11279231]

Stuehr D, Pou S, Rosen GM

Oxygen reduction by nitric-oxide synthases.

J. Biol. Chem. 276 (2001) 14533-6.

4  [PMID:21119059]

Foresi N, Correa-Aragunde N, Parisi G, Calo G, Salerno G, 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) 3816-30.