Control of citrate formation in rat liver mitochondria

Summary Measurements of citrate formation and endogenous adenine nucleotides in fluorocitrate-inhibited rat liver mitochondria respiring in the presence of 50 μM (−) palmitoyl carnitine and 250 μM malate have failed to support the suggestion that citrate synthase activity is controlled primarily by the intramitochondrial ATP level. A positive correlation was obtained between the redox state of the mitochondrial pyridine nucleotides and the rate of citrate formation, suggesting that at physiological malate concentrations, the rate of entry of acetyl CoA into the citric acid cycle is effectively controlled by oxalacetate availability. As acetyl CoA levels increase, and oxalacetate levels decrease, in rat liver with increased fatty acid availability (Williamson, Herczeg, Coles and Danish, 1966 ; Williamson, 1967) , increased ketogenesis accompanies the observed increase in the redox state of pyridine nucleotides in both the cytoplasmic and mitochondrial spaces. We suggest that the change in the redox state following increased fatty acid oxidation is a primary event preceding ketosis.