Effects of metabolic acidosis and starvation on the content of intermediary metabolites in rat kidney

1. Metabolite contents were determined in freeze-clamped kidney from acidotic and starved rats in order to elucidate the rate-controlling steps which are responsible for the acceleration of gluconeogenesis in these situations. 2. In the kidney of rats which were made mildly acidotic by replacing drinking water with 1.5% ammonium chloride for 7 to 10 days (when the plasma bicarbonate concentration was 20mm) the content of phosphoenolpyruvate was increased from the control value of 35 to 63nmol/g and that of 3-phosphoglycerate from 85 to 154nmol/g. 3. Similar but smaller changes in these metabolites occurred in the kidney of starved rats but there were no such changes in the kidney of rats 12h after an infusion of 0.25m-hydrochloric acid, although plasma bicarbonate concentration fell to about 10mm on this treatment. 4. The renal concentration of glucose 6-phosphate was not raised in rats that received ammonium chloride, but was increased in starved and acutely acidotic rats. 5. The concentrations of α-oxoglutarate, malate and citrate were less than half the normal value in the kidney of both groups of acidotic rats. These changes can be accounted for on the basis of equilibrium relationships among reversible reactions, particularly as a result of the rise in intracellular ammonia content. A less marked decrease in α-oxoglutarate and malate was found in the kidney of starved rats. 6. The renal cortical cytoplasmic oxaloacetate concentration was calculated to be decreased in acidotic and starved rats. 7. These results are discussed in the light of the known enhancement by acidosis and starvation of renal gluconeogenesis. In particular they support the suggestion that the phosphoenolpyruvate carboxykinase reaction is a site of control of gluconeogenesis in kidney in these conditions.