Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51)

Biochem Pharmacol. 1988 Jun 1;37(11):2267-71. doi: 10.1016/0006-2952(88)90591-6.

Abstract

The glutathione peroxidase activity of ebselen (PZ51) was studied using different hydroperoxidic substrates. The single progression curves obtained in the spectrophotometric test were processed by a computer to fit the integrated rate equation that describes the ping pong reaction of the Se glutathione peroxidase. Ebselen catalyzes the GSH peroxidase reaction with a mechanism that appears kinetically identical to the mechanism of the enzymes. The inactivation of the catalytic properties of ebselen by iodoacetate suggests that a selenol moiety is involved. Among the substrates tested, the best hydroperoxidic substrates are the hydroperoxy derivatives of phosphatidyl choline. Ebselen is active also on membrane hydroperoxides as does phospholipid hydroperoxide glutathione peroxidase but not glutathione peroxidase.

MeSH terms

  • Antioxidants / pharmacology*
  • Azoles / pharmacology*
  • Glutathione Peroxidase / pharmacology*
  • Hydrogen Peroxide / metabolism
  • Isoindoles
  • Kinetics
  • Lipid Peroxides / metabolism
  • Organoselenium Compounds*
  • Selenium / pharmacology*
  • Substrate Specificity

Substances

  • Antioxidants
  • Azoles
  • Isoindoles
  • Lipid Peroxides
  • Organoselenium Compounds
  • ebselen
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Selenium