Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization

Cell Mol Life Sci. 1999 Jul;55(8-9):1015-28. doi: 10.1007/s000180050352.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginase / antagonists & inhibitors
  • Arginase / metabolism*
  • Arginine / analogs & derivatives
  • Arginine / metabolism*
  • Biopterin / analogs & derivatives
  • Biopterin / metabolism
  • Calcium / antagonists & inhibitors
  • Calcium / physiology
  • Calmodulin / antagonists & inhibitors
  • Calmodulin / metabolism
  • Electron Transport
  • Enzyme Activation
  • Enzyme Induction
  • Enzyme Inhibitors / pharmacology
  • Free Radicals
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism*
  • Mice
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / metabolism*

Substances

  • Calmodulin
  • Enzyme Inhibitors
  • Free Radicals
  • Isoenzymes
  • Nitric Oxide Donors
  • Biopterin
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Arginase
  • sapropterin
  • Calcium