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NOS1
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<h2 id="function">Function</h2> <p><a href="/facts/Nitric_oxide_synthase/a474Vj5q">Nitric oxide synthases</a> (<a href="/facts/Enzyme_Commission_number/Y5GNLRKX">EC</a> <a href="https://enzyme.expasy.org/EC/1.14.13.39">1.14.13.39</a>) (NOSs) are a family of <a href="/facts/Synthase/39C9l6fN">synthases</a> that <a href="/facts/Catalysis/LPBS7TQC">catalyze</a> the production of <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> (NO) from <a href="/facts/L-arginine/y49Hdf1e">L-arginine</a>. 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 <a href="/facts/Neurotransmitter/LlpYFSU3">neurotransmitter</a> and may be involved in <a href="/facts/Long_term_potentiation/AbuJmBeo">long term potentiation</a>. It is implicated in <a href="/facts/Neurotoxicity/FrgTICfX">neurotoxicity</a> associated with <a href="/facts/Stroke/DwpjdzY0">stroke</a> and neurodegenerative diseases, neural regulation of smooth muscle, including <a href="/facts/Peristalsis/R6zzQb1d">peristalsis</a> and sphincter relaxation, and penile erection. NO is also responsible for <a href="/facts/Endothelium-derived_relaxing_factor/qkwQ0DvY">endothelium-derived relaxing factor</a> activity regulating blood pressure as produced from its related enzyme NOS3. In <a href="/facts/Macrophage/z7hkQu3o">macrophages</a>, 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 <a href="/facts/Nitric_oxide_synthase_2A/AmGzCqEf">macrophage NOS</a> are distinct isoforms.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> Both the neuronal and the macrophage forms are unusual among oxidative enzymes in requiring several electron donors: <a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">flavin adenine dinucleotide</a> (FAD), <a href="/facts/Flavin_mononucleotide/cWutCJmR">flavin mononucleotide</a> (FMN), <a href="/facts/NADPH/XMgmPQ5t">NADPH</a>, and <a href="/facts/Tetrahydrobiopterin/BYrDKeLl">tetrahydrobiopterin</a>.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p>It has been implicated in <a href="/facts/Asthma/7GkJvxn3">asthma</a>,<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a>,<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> <a href="/facts/Restless_leg_syndrome/XNn8sPDN">restless leg syndrome</a>,<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> and <a href="/facts/Psychostimulant/nmBdAXM5">psychostimulant</a> neurotoxicity. It has also been investigated with respect to <a href="/facts/Bipolar_disorder/aMDwXbV0">bipolar disorder</a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> and <a href="/facts/Air_pollution/zmk9Dy7S">air pollution</a> exposure.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>NOS1 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/DLG4/d23IStkv">DLG4</a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> and <a href="/facts/NOS1AP/TasanVan">NOS1AP</a>.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Nitric_oxide_synthase/a474Vj5q">Nitric oxide synthase</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Miyagoe-Suzuki Y, Takeda SI (2001). "Association of neuronal nitric oxide synthase (nNOS) with alpha1-syntrophin at the sarcolemma". <i>Microsc. Res. Tech</i>. 55 (3): 164–70. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1002%2Fjemt.1167">10.1002/jemt.1167</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11747091">11747091</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:28225242">28225242</a>.</li> <li>Waddington SN (2002). <a href="https://doi.org/10.1046%2Fj.1523-1755.2002.00236.x">"Arginase in glomerulonephritis"</a>. <i>Kidney Int</i>. 61 (3): 876–81. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1046%2Fj.1523-1755.2002.00236.x">10.1046/j.1523-1755.2002.00236.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11849441">11849441</a>.</li> <li>Rotilio G, Aquilano K, Ciriolo MR (2004). <a href="https://doi.org/10.1080%2F15216540310001628717">"Interplay of Cu,Zn superoxide dismutase and nitric oxide synthase in neurodegenerative processes"</a>. <i>IUBMB Life</i>. 55 (10–11): 629–34. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1080%2F15216540310001628717">10.1080/15216540310001628717</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/14711010">14711010</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:19518719">19518719</a>.</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Kishimoto J, Spurr N, Liao M, Lizhi L, Emson P, Xu W (November 1992). "Localization of brain nitric oxide synthase (NOS) to human chromosome 12". Genomics. 14 (3): 802–4. doi:10.1016/S0888-7543(05)80192-2. PMID 1385308. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR (April 1993). "Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes". Proc. Natl. Acad. Sci. U.S.A. 90 (8): 3491–5. Bibcode:1993PNAS...90.3491G. doi:10.1073/pnas.90.8.3491. PMC 46326. PMID 7682706. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46326" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46326</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Lowenstein CJ, Glatt CS, Bredt DS, Snyder SH (August 1992). "Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme". Proc. Natl. Acad. Sci. U.S.A. 89 (15): 6711–5. Bibcode:1992PNAS...89.6711L. doi:10.1073/pnas.89.15.6711. PMC 49573. PMID 1379716. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49573" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49573</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: NOS1 Nitric oxide synthase 1 (neuronal)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4843" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4843</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Grasemann H, Yandava CN, Drazen JM (December 1999). "Neuronal NO synthase (NOS1) is a major candidate gene for asthma". Clin. Exp. Allergy. 29. 29 (Suppl 4): 39–41. PMID 10641565. Archived from the original on 2013-01-05. <a href="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" target="_blank">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</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Leung TF, Liu EK, Tang NL, Ko FW, Li CY, Lam CW, Wong GW (October 2005). "Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children". Clin. Exp. Allergy. 35 (10): 1288–94. doi:10.1111/j.1365-2222.2005.02342.x. PMID 16238787. S2CID 24110873. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Shinkai T, Ohmori O, Hori H, Nakamura J (2002). "Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia". Mol. Psychiatry. 7 (6): 560–3. doi:10.1038/sj.mp.4001041. PMID 12140778. <a href="https://doi.org/10.1038%2Fsj.mp.4001041" target="_blank">https://doi.org/10.1038%2Fsj.mp.4001041</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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 (March 2006). "A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function". Mol. Psychiatry. 11 (3): 286–300. doi:10.1038/sj.mp.4001779. PMID 16389274. <a href="https://doi.org/10.1038%2Fsj.mp.4001779" target="_blank">https://doi.org/10.1038%2Fsj.mp.4001779</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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 (February 2008). "Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome". Mov. Disord. 23 (3): 350–8. doi:10.1002/mds.21647. PMID 18058820. S2CID 42425890. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Buttenschön HN, Mors O, Ewald H, McQuillin A, Kalsi G, Lawrence J, Gurling H, Kruse TA (January 2004). "No association between a neuronal nitric oxide synthase (NOS1) gene polymorphism on chromosome 12q24 and bipolar disorder". Am. J. Med. Genet. B Neuropsychiatr. Genet. 124B (1): 73–5. doi:10.1002/ajmg.b.20040. PMID 14681919. S2CID 45596789. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Steenackers W, De Herdt E, De Boever P, Bos I, Int Panis L (2013). "Neuroinflammation induced by air pollution: gene expression analysis in laboratory animals". Master Thesis, GROUP T – Leuven Engineering College. <a href="https://www.researchgate.net/publication/236162904" target="_blank">https://www.researchgate.net/publication/236162904</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH (January 1998). "CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95". Neuron. 20 (1): 115–24. doi:10.1016/S0896-6273(00)80439-0. PMID 9459447. S2CID 14613261. <a href="https://doi.org/10.1016%2FS0896-6273%2800%2980439-0" target="_blank">https://doi.org/10.1016%2FS0896-6273%2800%2980439-0</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (March 1996). "Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains". Cell. 84 (5): 757–67. doi:10.1016/S0092-8674(00)81053-3. PMID 8625413. S2CID 15834673. <a href="https://doi.org/10.1016%2FS0092-8674%2800%2981053-3" target="_blank">https://doi.org/10.1016%2FS0092-8674%2800%2981053-3</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Jaffrey SR, Snowman AM, Eliasson MJ, Cohen NA, Snyder SH (January 1998). "CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95". Neuron. 20 (1): 115–24. doi:10.1016/S0896-6273(00)80439-0. PMID 9459447. S2CID 14613261. <a href="https://doi.org/10.1016%2FS0896-6273%2800%2980439-0" target="_blank">https://doi.org/10.1016%2FS0896-6273%2800%2980439-0</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> </ol>