Glutathione metabolism and glucose 6-phosphate dehydrogenase activity in experimental liver injury.
Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH) following an intragastric administration of carbon tetrachloride (CCl4) to rats. Oxidized glutathione (GSSG) also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2.), glutathione peroxidase (EC 1.11.1.9) and malic enzyme (EC 1.1.1.40) activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D010084:Oxidation-Reduction; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008298:Maleates; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; C014476:diethyl maleate; D005978:Glutathione