In Vivo Regulation of Hepatic Glutathione Synthesis: Effects of Food Deprivation or Glutathione Depletion by Electrophilic Compounds

Abstract

The increased glutathione turnover that occurs during fasting results from two mechanisms. Because of a decrease in the intrahepatic free glutathione: mixed disulfide ratio, which is apparently mediated by c-AMP, the free glutathione pool contracts and turns over more rapidly in order to maintain glutathione synthesis. In addition, glutathione consumption via the gamma-glutamyl cycle apparently is increased during fasting. Additional data indicate that an inability to stimulate further the rate of glutathione synthesis during fasting, rather than a reduction in glutathione synthesis are previously postulated, probably explains the increased susceptibility of fasted animals to tissue attack by electrophilic drug metabolites.