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Nitric oxide synthase
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=== eNOS === {{Main|Endothelial NOS}} Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3), generates NO in [[blood vessel]]s and is involved with regulating vascular function. The gene coding for eNOS is located on Chromosome 7.<ref name="Nitric oxide synthases in mammals" /> A constitutive Ca<sup>2+</sup> dependent NOS provides a basal release of NO. eNOS localizes to caveolae, a plasma membrane domain primarily composed of the protein [[caveolin 1]], and to the Golgi apparatus. These two eNOS populations are distinct, but are both necessary for proper NO production and cell health.<ref name ="pmid32152543">{{cite journal |vauthors = Maulik SJ, Junyi Z, Aneesh TV, Yamuna K | title = A DNA-based fluorescent probe maps NOS3 activity with subcellular spatial resolution | journal = Nat. Chem. Biol. | issue = 6 | pages = 660β6 | date=March 2020 | volume = 16 | pmid = 32152543 | doi = 10.1038/s41589-020-0491-3| s2cid = 212642840 }}</ref> eNOS localization to endothelial membranes is mediated by cotranslational N-terminal [[myristoylation]] and post-translational [[palmitoylation]].<ref name="pmid9199168">{{cite journal |vauthors=Liu J, Hughes TE, Sessa WC | title = The First 35 Amino Acids and Fatty Acylation Sites Determine the Molecular Targeting of Endothelial Nitric Oxide Synthase into the Golgi Region of Cells: A Green Fluorescent Protein Study | journal = J. Cell Biol. | volume = 137 | issue = 7 | pages = 1525β35 |date=June 1997 | pmid = 9199168 | pmc = 2137822 | doi = 10.1083/jcb.137.7.1525 }}</ref> As an essential co-factor for nitric oxide synthase, [[tetrahydrobiopterin]] (BH4) supplementation has shown beneficial results for the treatment of [[endothelial dysfunction]] in animal experiments and clinical trials, although the tendency of BH4 to become oxidized to BH2 remains a problem.<ref name="pmid29596860">{{cite journal | vauthors = Yuyun MF, Ng LL, Ng GA | title=Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy? | journal= Microvascular Research | volume=119 | pages=7β12 | year=2018 | doi= 10.1016/j.mvr.2018.03.012 | pmid=29596860}}</ref>
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