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 c ells. 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 fo rmation as well as NOS stability are finely regulated by Ca2+/calmodulin in teractions, by the cofactor tetrahydrobiopterin, and by substrate availabil ity. Strong interactions between the L-arginine-metabolizing enzymes are cl early demonstrated by competition between NOSs and arginases for L-arginine utilization, and by potent inhibition of arginase activity by N-omega-hydr oxy-L-arginine, an intermediate in the L-arginine to NO pathway.