The effect of divalent cations on neuronal nitric oxide synthase activity

Toxicological Sciences : an Official Journal of the Society of Toxicology
John WeaverGerald M Rosen

Abstract

Neuronal nitric oxide synthase (NOS I) is a Ca(2+)/calmodulin-binding enzyme that generates nitric oxide (NO*) and L-citrulline from the oxidation of L-arginine, and superoxide (O(2)*(-)) from the one-electron reduction of oxygen (O(2)). Nitric oxide in particular has been implicated in many physiological processes, including vasodilator tone, hypertension, and the development and properties of neuronal function. Unlike Ca(2+), which is tightly regulated in the cell, many other divalent cations are unfettered and can compete for the four Ca(2+) binding sites on calmodulin. The results presented in this article survey the effects of various divalent metal ions on NOS I-mediated catalysis. As in the case of Ca(2+), we demonstrate that Ni(2+), Ba(2+), and Mn(2+) can activate NOS I to metabolize L-arginine to L-citrulline and NO*, and afford O(2)*(-) in the absence of L-arginine. In contrast, Cd(2+) did not activate NOS I to produce either NO* or O(2)*(-), and the combination of Ca(2+) and either Cd(2+), Ni(2+), or Mn(2+) inhibited enzyme activity. These interactions may initiate cellular toxicity by negatively affecting NOS I activity through production of NO*, O(2)*(-) and products derived from these free radicals.

Citations

Jan 9, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·María José González-MuñozSara Bastida
Jun 28, 2006·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Vassilios TzotzesHaris Carageorgiou
May 20, 2008·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Seiko SusukiHirofumi Kai
Sep 25, 2007·Biochimica Et Biophysica Acta·Donald E SprattJ Guy Guillemette
Feb 21, 2006·Neurochemistry International·Chun-Jung ChenJian-Hong Chen

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