|Gene:||NOS1||Accession Number: G-8745 (MetaCyc)|
Synonyms: nitric-oxide synthase, brain, neural NOS
Species: Homo sapiens
Subunit composition of
nNOS = [NOS1]2
NOS1 monomer = NOS1
Nitric oxide (NO) is the active moiety of the endothelium-derived relaxing factor. In the vasculature NO relaxes smooth muscle and inhibits platelet and leukocyte adhesion. Outside the vasculature, NO participates in the immunologic response to infection and serves as a neurotransmitter.
Nitric oxide synthases (NOSs) are a family of enzymes responsible for the synthesis of nitric oxide from L-arginine and oxygen. The reaction forms citrulline as a by product, which is usually recycled back to arginine for the production of more NO. The three main human NOS enzyme isoforms are nNOS (for neuronal NOS), iNOS (for inducible NOS) and eNOS (for epithelial NOS). They are also known as types I, II and III. These enzymes are well studied, and possess differing cellular distribution and regulatory mechanisms.
All of the isoforms have requirement for multiple factors, including tetrahydrobiopterin [Kwon89, Tayeh89], FMN [Stuehr91], FAD [Stuehr90, Stuehr91], a thiol [Stuehr90] and Ca2+ [Schmidt92]. They all bind the calcium-binding protein calmodulin [Schmidt92, Bredt90] and contain heme [Forstermann94].
nNOS is constitutively expressed and is present in central and peripheral neuronal cells and some epithelial cells. It is regulated by the binding of calmodulin at elevated Ca2+ concentrations. Its functions include long-term regulation of synaptic transmission in the central nervous system, central regulation of blood pressure, smooth muscle relaxation, and vasodilation via peripheral nitrergic nerves [Forstermann94].
Molecular Weight of Polypeptide: 160 kD (experimental) [Park96 ]
Unification Links: ArrayExpress:P29475 , Mint:MINT-122019 , ModBase:P29475 , PhosphoSite:P29475 , Pride:P29475 , Protein Model Portal:P29475 , SMR:P29475 , String:9606.ENSP00000320758 , Swiss-Model:P29475 , UniProt:P29475
Relationship Links: Entrez-Nucleotide:PART-OF:U17327 , InterPro:IN-FAMILY:IPR001094 , InterPro:IN-FAMILY:IPR001433 , InterPro:IN-FAMILY:IPR001478 , InterPro:IN-FAMILY:IPR001709 , InterPro:IN-FAMILY:IPR003097 , InterPro:IN-FAMILY:IPR004030 , InterPro:IN-FAMILY:IPR008254 , InterPro:IN-FAMILY:IPR012144 , InterPro:IN-FAMILY:IPR017927 , InterPro:IN-FAMILY:IPR017938 , InterPro:IN-FAMILY:IPR023173 , Panther:IN-FAMILY:PTHR19384:SF5 , Pfam:IN-FAMILY:PF00175 , Pfam:IN-FAMILY:PF00258 , Pfam:IN-FAMILY:PF00595 , Pfam:IN-FAMILY:PF00667 , Pfam:IN-FAMILY:PF02898 , Prints:IN-FAMILY:PR00369 , Prints:IN-FAMILY:PR00371 , Prosite:IN-FAMILY:PS50106 , Prosite:IN-FAMILY:PS50902 , Prosite:IN-FAMILY:PS51384 , Prosite:IN-FAMILY:PS60001 , Smart:IN-FAMILY:SM00228
Enzymatic reaction of: nitric-oxide synthase (nNOS)
EC Number: 220.127.116.11
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.
The reaction is physiologically favored in the direction shown.
Blau: Blau N, Bonafe L, Thony B "Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency." Mol Genet Metab 74(1-2);172-85. PMID: 11592814
Cho98: Cho SH, Na JU, Youn H, Hwang CS, Lee CH, Kang SO (1998). "Tepidopterin, 1-O-(L-threo-biopterin-2'-yl)-beta-N-acetylglucosamine from Chlorobium tepidum." Biochim Biophys Acta 1379(1);53-60. PMID: 9468332
Chung00: Chung HJ, Kim YA, Kim YJ, Choi YK, Hwang YK, Park YS (2000). "Purification and characterization of UDP-glucose:tetrahydrobiopterin glucosyltransferase from Synechococcus sp. PCC 7942." Biochim Biophys Acta 1524(2-3);183-8. PMID: 11113566
Forstermann94: Forstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H (1994). "Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions." Hypertension 23(6 Pt 2);1121-31. PMID: 7515853
Hall94: Hall AV, Antoniou H, Wang Y, Cheung AH, Arbus AM, Olson SL, Lu WC, Kau CL, Marsden PA (1994). "Structural organization of the human neuronal nitric oxide synthase gene (NOS1)." J Biol Chem 269(52);33082-90. PMID: 7528745
Maier95: Maier J, Ninnemann H (1995). "Biosynthesis of pteridines in Neurospora crassa, Phycomyces blakesleeanus and Euglena gracilis: detection and characterization of biosynthetic enzymes." Photochem Photobiol 61(1);43-53. PMID: 7899493
Mataga91: Mataga N, Imamura K, Watanabe Y (1991). "6R-tetrahydrobiopterin perfusion enhances dopamine, serotonin, and glutamate outputs in dialysate from rat striatum and frontal cortex." Brain Res 551(1-2);64-71. PMID: 1680529
Schallreuter94: Schallreuter KU, Wood JM, Pittelkow MR, Gutlich M, Lemke KR, Rodl W, Swanson NN, Hitzemann K, Ziegler I (1994). "Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin." Science 263(5152);1444-6. PMID: 8128228
Schmidt92: Schmidt HH, Smith RM, Nakane M, Murad F (1992). "Ca2+/calmodulin-dependent NO synthase type I: a biopteroflavoprotein with Ca2+/calmodulin-independent diaphorase and reductase activities." Biochemistry 31(12);3243-9. PMID: 1372827
Stuehr91: Stuehr DJ, Cho HJ, Kwon NS, Weise MF, Nathan CF (1991). "Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein." Proc Natl Acad Sci U S A 88(17);7773-7. PMID: 1715579
Tanaka89a: Tanaka K, Kaufman S, Milstien S (1989). "Tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, is synthesized by and regulates proliferation of erythroid cells." Proc Natl Acad Sci U S A 86(15);5864-7. PMID: 2762302
Tayeh89: Tayeh MA, Marletta MA (1989). "Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor." J Biol Chem 264(33);19654-8. PMID: 2584186
Wang11e: Wang H, Yang B, Hao G, Feng Y, Chen H, Feng L, Zhao J, Zhang H, Chen YQ, Wang L, Chen W (2011). "Biochemical characterization of the tetrahydrobiopterin synthesis pathway in the oleaginous fungus Mortierella alpina." Microbiology 157(Pt 11);3059-70. PMID: 21852350
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