The Interrelationships of the Various Pathways Forming Gluconeogenic Precursors in Guinea Pig Liver Mitochondria

Previous work has shown that the synthesis of phosphoenolpyruvate by mitochondria from guinea pig liver was controlled by the availability of intramitochondrial oxalacetate. In this study, the livers of fed and fasted guinea pigs were freeze clamped to identify those factors associated with enhanced rates of gluconeogenesis in vivo. The oxidation-reduction potential of the intramitochondrial nicotinamide adenine dinucleotides was markedly shifted toward oxidation in livers of fasted as compared with livers of fed guinea pigs. This transition in the oxidation-reduction potential was recreated in incubations with isolated guinea pig liver mitochondria, and the relative rates of malate, aspartate, and P-enolpyruvate synthesis from a variety of substrates were followed. The rate of P-enolpyruvate formation relative to the rates of aspartate and malate formation was markedly increased at oxidation-reduction potentials resembling those found in the livers of fasted as compared with livers of fed guinea pigs. Those factors regulating the formation of the various gluconeogenic precursors are discussed and the interrelationships of these mechanisms are analyzed.