Regulation of glutamate metabolism by renal cortical mitochondria

Abstract

Isolated rat renal cortical mitochondria were used to investigate the effect of acid-base perturbations on glutamate metabolism. Glutamate supplied to the mitochondria in the incubation medium is not metabolized in the same fashion as glutamate formed intramitochondrially from glutamine. Therefore 1.0 or 5.0 mM glutamine was used as substrate and the N-containing end products were quantitated to determine the paths of glutamate metabolism. Chronic acidosis increased the rate of glutamate deamination and increased intramitochondrial glutamate concentration. Since studies were carried out at saturating concentrations of intramitochondrial glutamate, the increase in glutamate deamination is attributable to an increase in the activity of glutamate dehydrogenase. When mitochondria from normal rats were incubated at pH 7.0, 7.4 or 7.7, glutamate deamination decreased as pH was diminished. Intramitochondrial glutamate concentration was unchanged. A low medium pH altered glutamate metabolism by decreasing the activity of glutamate dehydrogenase. Glutamate transamination was decreased by chronic acidosis and by incubation of normal mitochondria in a low pH. Additional studies with the transaminase inhibitor aminooxyacetate suggest that transamination of glutamate has little overall influence on mitochondrial ammonia metabolism.