Regulation of Phosphoenolpyruvate Metabolism in Mitochondria from Guinea Pig Liver

Previous studies by us have shown that respiring guinea pig liver mitochondria can synthesize P-enolpyruvate from a variety of ordinarily available carbon intermediates. In this study, dinitrophenol was found to reduce substantially P-enolpyruvate formation owing to a deficiency of intramitochondrial ATP, and this reduction could not be relieved by stimultaneous substrate level phosphorylation of GDP. Ketone bodies were utilized to alter the oxidation-reduction state of the intramitochondrial pyridine nucleotides. These variations produced large changes in the rates of P-enolpyruvate formation, citrate synthesis, and malate formation. It is concluded that the ultimate source of high energy phosphate for P-enolpyruvate synthesis is the intramitochondrial pool of ATP rather than the substrate level phosphorylation of GDP. In addition, the ratio of ATP to ADP and the kinetic behavior of nucleoside diphosphokinase are found to control the rate and direction of P-enolpyruvate metabolism. A second control factor for P-enolpyruvate synthesis is the oxidation-reduction state of the pyridine nucleotides acting upon the equilibrium between malate and oxalacetate.