NOS1

{{Short description|Protein-coding gene in the species Homo sapiens}}

Nitric oxide synthase 1 (neuronal), also known as NOS1, is an enzyme that in humans is encoded by the NOS1 gene.{{cite journal | vauthors = Kishimoto J, Spurr N, Liao M, Lizhi L, Emson P, Xu W | title = Localization of brain nitric oxide synthase (NOS) to human chromosome 12 | journal = Genomics | volume = 14 | issue = 3 | pages = 802–4 | date = November 1992 | pmid = 1385308 | doi = 10.1016/S0888-7543(05)80192-2 }}{{cite journal | vauthors = Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR | title = Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 8 | pages = 3491–5 | date = April 1993 | pmid = 7682706 | pmc = 46326 | doi = 10.1073/pnas.90.8.3491 | bibcode = 1993PNAS...90.3491G | doi-access = free }}

Function

Nitric oxide synthases ({{EC number|1.14.13.39}}) (NOSs) are a family of synthases that catalyze the production of nitric oxide (NO) from L-arginine. NO is a chemical messenger with diverse functions throughout the body depending on its enzymatic source and tissue localization. In the brain and peripheral nervous system, where NOS1 is largely present, NO displays many properties of a neurotransmitter and may be involved in long term potentiation. It is implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis and sphincter relaxation, and penile erection. NO is also responsible for endothelium-derived relaxing factor activity regulating blood pressure as produced from its related enzyme NOS3. In macrophages, NO mediates tumoricidal and bactericidal actions, as produced from its related enzyme NOS2. Various pharmacological inhibitors of NO synthases (NOS) block these effects, but further distinction of their function has been elucidated by animal models in which these specific genes have been inactivated. Neuronal NOS (NOS1), Endothelial NOS (NOS3), and Inducible NOS macrophage NOS are distinct isoforms.{{cite journal | vauthors = Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH | title = Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 15 | pages = 6711–5 | date = August 1992 | pmid = 1379716 | pmc = 49573 | doi = 10.1073/pnas.89.15.6711 | bibcode = 1992PNAS...89.6711L | doi-access = free }} Both the neuronal and the macrophage forms are unusual among oxidative enzymes in requiring several electron donors: flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), NADPH, and tetrahydrobiopterin.{{cite web | title = Entrez Gene: NOS1 Nitric oxide synthase 1 (neuronal) | url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4843}}

Clinical significance

It has been implicated in asthma,{{cite journal | vauthors = Grasemann H, Yandava CN, Drazen JM | title = Neuronal NO synthase (NOS1) is a major candidate gene for asthma | journal = Clin. Exp. Allergy | volume = 29 | pages = 39–41 | date = December 1999 | pmid = 10641565 | url = http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=1999&volume=29&issue=&spage=39 | archive-url = https://archive.today/20130105111910/http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=1999&volume=29&issue=&spage=39 | url-status = dead | archive-date = 2013-01-05 | series = 29 | issue = Suppl 4 }}{{cite journal | vauthors = Leung TF, Liu EK, Tang NL, Ko FW, Li CY, Lam CW, Wong GW | title = Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children | journal = Clin. Exp. Allergy | volume = 35 | issue = 10 | pages = 1288–94 | date = October 2005 | pmid = 16238787 | doi = 10.1111/j.1365-2222.2005.02342.x | s2cid = 24110873 }} schizophrenia,{{cite journal | vauthors = Shinkai T, Ohmori O, Hori H, Nakamura J | title = Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia | journal = Mol. Psychiatry | volume = 7 | issue = 6 | pages = 560–3 | year = 2002 | pmid = 12140778 | doi = 10.1038/sj.mp.4001041 | doi-access = free }}{{cite journal | vauthors = Reif A, Herterich S, Strobel A, Ehlis AC, Saur D, Jacob CP, Wienker T, Töpner T, Fritzen S, Walter U, Schmitt A, Fallgatter AJ, Lesch KP | title = A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function | journal = Mol. Psychiatry | volume = 11 | issue = 3 | pages = 286–300 | date = March 2006 | pmid = 16389274 | doi = 10.1038/sj.mp.4001779 | doi-access = free }} restless leg syndrome,{{cite journal | vauthors = Winkelmann J, Lichtner P, Schormair B, Uhr M, Hauk S, Stiasny-Kolster K, Trenkwalder C, Paulus W, Peglau I, Eisensehr I, Illig T, Wichmann HE, Pfister H, Golic J, Bettecken T, Pütz B, Holsboer F, Meitinger T, Müller-Myhsok B | title = Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome | journal = Mov. Disord. | volume = 23 | issue = 3 | pages = 350–8 | date = February 2008 | pmid = 18058820 | doi = 10.1002/mds.21647 | s2cid = 42425890 }} and psychostimulant neurotoxicity. It has also been investigated with respect to bipolar disorder{{cite journal | vauthors = Buttenschön HN, Mors O, Ewald H, McQuillin A, Kalsi G, Lawrence J, Gurling H, Kruse TA | title = No association between a neuronal nitric oxide synthase (NOS1) gene polymorphism on chromosome 12q24 and bipolar disorder | journal = Am. J. Med. Genet. B Neuropsychiatr. Genet. | volume = 124B | issue = 1 | pages = 73–5 | date = January 2004 | pmid = 14681919 | doi = 10.1002/ajmg.b.20040 | s2cid = 45596789 }} and air pollution exposure.{{cite journal | vauthors = Steenackers W, De Herdt E, De Boever P, Bos I, Int Panis L| title = Neuroinflammation induced by air pollution: gene expression analysis in laboratory animals | journal = Master Thesis, GROUP T – Leuven Engineering College | year = 2013 | url = https://www.researchgate.net/publication/236162904}}

Interactions

NOS1 has been shown to interact with DLG4{{cite journal | vauthors = Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH | title = CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95 | journal = Neuron | volume = 20 | issue = 1 | pages = 115–24 | date = January 1998 | pmid = 9459447 | doi = 10.1016/S0896-6273(00)80439-0 | s2cid = 14613261 | doi-access = free }}{{cite journal | vauthors = Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS | title = Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains | journal = Cell | volume = 84 | issue = 5 | pages = 757–67 | date = March 1996 | pmid = 8625413 | doi = 10.1016/S0092-8674(00)81053-3 | s2cid = 15834673 | doi-access = free }} and NOS1AP.

NOS1

Function

Clinical significance

Interactions

See also

References

Further reading