Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization.
Nitric oxide (NO) is a recently discovered mediator produced by mammalian cells. It plays a key role in neurotransmission, control of blood pressure, and cellular defense mechanisms. Nitric oxide synthases (NOSs) catalyze the oxidation of L-arginine to NO and L-citrulline. NOSs are unique enzymes in that they possess on the same polypeptidic chain a reductase domain and an oxygenase domain closely related to cytochrome P450s. NO and superoxide formation as well as NOS stability are finely regulated by Ca2+/calmodulin interactions, by the cofactor tetrahydrobiopterin, and by substrate availability. Strong interactions between the L-arginine-metabolizing enzymes are clearly demonstrated by competition between NOSs and arginases for L-arginine utilization, and by potent inhibition of arginase activity by N(omega)-hydroxy-L-arginine, an intermediate in the L-arginine to NO pathway.
Boucher
J L
JL
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Paris, France. boucher@bisance.citi2.fr
Moali
C
C
Tenu
J P
JP
D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004579:Electron Transport; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D002147:Calmodulin; D004791:Enzyme Inhibitors; D005609:Free Radicals; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D001708:Biopterins; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; C003402:sapropterin; D002118:Calcium