R. Hanson, P. Ray, P. Walter
Aug 25, 1969
Citations
1
Influential Citations
48
Citations
Quality indicators
Journal
The Journal of biological chemistry
Abstract
Abstract Quinaldic acid and 5-methoxyindole-2-carboxylic acid inhibited gluconeogenesis from lactate, but not from fructose in both the intact rat and in the isolated perfused rat liver. In fed rats both inhibitors are glycogenolytic; in fasted rats 5-methoxyindole-2-carboxylic acid caused hypoglycemia and both inhibitors caused severe hypoglycemia in adrenalectomized rats. Treatment of fasted rats with either inhibitor resulted in increased concentrations of plasma nonesterified fatty acids, decreased levels of blood ketone bodies, as well as a decrease in the ratio of β-hydroxybutyrate to acetoacetate, and elevated hepatic concentrations of lactate, pyruvate, phosphoenolpyruvate, and 2- and 3-phosphoglycerate. The hepatic concentrations of malate, citrate, aspartate, triose phosphates, and hexose phosphates were decreased or normal. Lactate and pyruvate accumulated in the blood and kidneys of rats treated with 5-methoxyindole-2-carboxylic acid, but blood and kidney metabolite concentrations remained normal in rats given quinaldic acid. In agreement with Bauman and Hill (Biochemistry, 7, 1322 (1968)) both quinaldic acid and methoxyindolecarboxylate inhibited oxidation and carboxylation of pyruvate by rat liver mitochondria. Octanoate restored both processes in mitochondria treated with either inhibitor and prevented or reversed their inhibition of gluconeogenesis from lactate in the perfused liver. These observations, together with the observed changes in hepatic metabolites of rats treated with methoxyindolecarboxylate or quinaldate, suggest that inhibition of hepatic mitochondrial pyruvate metabolism is responsible for inhibition of gluconeogenesis by both substances.