EC - Nitric-oxide synthase (NADPH)

  IntEnz view ENZYME view

IntEnz Enzyme Nomenclature


Accepted name:
nitric-oxide synthase (NADPH)
Other names:
NADPH-diaphorase [ambiguous]
NO synthase [ambiguous]
endothelium-derived relaxation factor-forming enzyme [ambiguous]
endothelium-derived relaxing factor synthase [ambiguous]
nitric oxide synthetase [ambiguous]
nitric-oxide synthetase
NOS (gene name)
Systematic name:
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)




The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains 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. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC, nitric-oxide synthase (flavodoxin).

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004517
CAS Registry Number: 125978-95-2
UniProtKB/Swiss-Prot: (35) [show] [UniProt]


  1. Bredt, D.S. and Snyder, S.H.
    Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.
    Proc. Natl. Acad. Sci. USA 87: 682-685 (1990). [PMID: 1689048]
  2. Stuehr, D. J., Kwon, N. S., Nathan, C. F., Griffith, O. W., Feldman, P. L., Wiseman, J.
    Nomega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine.
    J. Biol. Chem. 266: 6259-6263 (1991). [PMID: 1706713]
  3. Stuehr, D., Pou, S., Rosen, G. M.
    Oxygen reduction by nitric-oxide synthases.
    J. Biol. Chem. 276: 14533-14536 (2001). [PMID: 11279231]
  4. Agapie, T., Suseno, S., Woodward, J. J., Stoll, S., Britt, R. D., Marletta, M. A.
    NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum.
    Proc. Natl. Acad. Sci. U.S.A. 106: 16221-16226 (2009). [PMID: 19805284]
  5. 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: 3816-3830 (2010). [PMID: 21119059]

[EC created 1992, modified 2012, modified 2017]