In vivo regulation of hepatic glutathione synthesis: effects of food deprivation or glutathione depletion by electrophilic compounds.
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.
D000082:Acetaminophen / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005215:Fasting; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000082:Acetaminophen; D005978:Glutathione