Inhibition of carbon dioxide fixation by lead acetate in rat liver mitochondria.
These studies were undertaken to determine the mechanism by which intravenously administered lead salts inhibit hepatic gluconeogenesis. Within 1 h after the intravenous administration of lead acetate (10 mg), there is 97% inhibition of CO2 fixation in isolated rat liver mitochondria. This effect is concentration-dependent. The induction of phosphoenolpyruvate carboxykinase activity observed with starvation was also inhibited by intravenously administered lead acetate, but the activities of pyruvate kinase, glucose 6-phosphate dehydrogenase and pyruvate carboxylase were unaffected, as was the oxidation of palmitate and palmitoyl-CoA by mitochondria from Pb2+-treated animals. The addition of reduced glutathione to mitochondria from Pb2+-treated animals had no effect on the inhibited CO2 fixation. ATP concentrations in mitochondria from Pb2+-treated animals are decreased and the dose-response relationships for the effect of Pb2+ on CO2 fixation and ATP concentrations correspond. We conclude that the decrease in mitochondrial ATP in Pb2+-treated animals is probably responsible for the marked inhibition ov CO2 fixation, and hence the impairment of gluconeogenesis from alanine, lactate and pyruvate observed by others.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000963:Antimetabolites; D002245:Carbon Dioxide / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D051381:Rats; D013217:Starvation
D000963:Antimetabolites; D002245:Carbon Dioxide; D007854:Lead; D000255:Adenosine Triphosphate; D010729:Phosphoenolpyruvate Carboxykinase (GTP)