title: Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline.
abstract: Nitric oxide (NO) is synthesized by a number of cells from a guanidino nitrogen atom of L-arginine by the action of either constitutive or inducible NO synthases, both of which form citrulline as a co-product. We have determined the source of the oxygen in both NO and in citrulline formed by the constitutive NO synthase from the vascular endothelium and brain and by the inducible NO synthase from the murine macrophage cell line J774. All these enzymes incorporate molecular oxygen both into NO and into citrulline. Furthermore, activated J774 cells form NO from omega-hydroxyl-L-arginine, confirming the proposal that this compound is an intermediate in the biosynthesis of NO.
authors.affiliation: Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Leone
authors.forename: R M
authors.initials: RM
authors.lastname: Palmer
authors.forename: R G
authors.initials: RG
authors.lastname: Knowles
authors.forename: P L
authors.initials: PL
authors.lastname: Francis
authors.forename: D S
authors.initials: DS
authors.lastname: Ashton
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001921:Brain / Q000201:enzymology*; D002460:Cell Line; D002956:Citrulline / Q000302:isolation & purification / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology*; D004790:Enzyme Induction; D007553:Isotope Labeling / Q000379:methods; D013058:Mass Spectrometry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000378:metabolism*; D010103:Oxygen Isotopes; D051381:Rats; D013552:Swine
chemical_list: D010103:Oxygen Isotopes; D002956:Citrulline; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen