Inhibition of carbon dioxide fixation by lead acetate in rat liver mitochondria

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Abstract
These studies were undertaken to determine the mechanism by which i.v. administered Pb salts inhibit hepatic gluconeogenesis. Within 1 h after the i.v. 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 [EC 4.1.1.32] activity observed with starvation was also inhibited by i.v. administered lead acetate, but the activities of pyruvate kinase [EC 2.7.1.40], glucose 6-phosphate dehydrogenase [EC 1.1.1.49] and pyruvate carboxylase [EC 6.4.1.1] 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. The decrease in mitochondrial ATP in Pb2+-treated animals is probably responsible for the marked inhibition of CO2 fixation, and hence the impairment of gluconeogenesis from alanine, lactate and pyruvate observed by others.