title: Ca2+/calmodulin-regulated nitric oxide synthases.
abstract: NO synthase (NOS) catalyzes the oxidation of L-arginine to L-citrulline and nitric oxide (NO) or a NO-releasing compound. At least three isoforms of NOS exist (types I-III). The activities of the type I isoform purified from brain and the type III isoform purified from endothelial cells are regulated by the intracellular free calcium concentration ([Ca2+]i) and the Ca(2+)-binding protein calmodulin. At resting [Ca2+]i, both isozymes are inactive; they become fully active at [Ca2+]i greater than or equal to 500 nM Ca2+. Longer lasting increases in [Ca2+]i may downregulate NO formation, for in vitro phosphorylation by Ca2+/calmodulin protein kinase II decreases the Vmax of NOS. Besides the conversion of L-arginine, type I NOS, Ca2+/calmodulin dependently, generates H2O2 and reduces cytochrome c/P450. Other redox activities, i.e. the reduction of nitroblue tetrazolium to diformazan (NADPH-diaphorase) or of quinoid-dihydrobiopterin to tetrahydrobiopterin, by NOS appear to be Ca2+/calmodulin-independent.
authors.affiliation: Northwestern University Medical School, Chicago.
authors.forename: H H
authors.initials: HH
authors.lastname: Schmidt
authors.forename: J S
authors.initials: JS
authors.lastname: Pollock
authors.forename: M
authors.initials: M
authors.lastname: Nakane
authors.forename: U
authors.initials: U
authors.lastname: Förstermann
authors.forename: F
authors.initials: F
authors.lastname: Murad
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D019001:Nitric Oxide Synthase
chemical_list: D002147:Calmodulin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002118:Calcium