Ca2+ calmodulin-regulated nitric oxide synthases

Academic Article

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 Ca2+-binding protein calmodulin. At resting [Ca2+]i, both isozymes are inactive; they become fully active at [Ca2+]i ≥ 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. © 1992.
  • Published In

  • Cell Calcium  Journal
  • Digital Object Identifier (doi)

    Author List

  • Schmidt HHHW; Pollock JS; Nakane M; Förstermann U; Murad F
  • Start Page

  • 427
  • End Page

  • 434
  • Volume

  • 13
  • Issue

  • 6-7