Effect of pH on metabolism of the glutamine carbon skeleton by renal cortical mitochondria

Abstract

1. 1. To determine the effect of altered acid-base homeostasis on the intramitochondrial metabolism of the glutamine carbon skeleton 14CO2 production from [U-14C]glutamine by isolated rat renal cortical mitochondria was measured.2. 2. Mitochondria from rats with chronic metabolic acidosis either showed no change or diminished 14CO2 production in comparison with pair fed controls.3. 3. By contrast, when the pH of the medium incubating mitochondria from normal rats was manipulated (pH 7.0, 7.4, 7.7), 14CO2 production was clearly altered, but the direction and magnitude of the change depended on the glutamine concentration used (0.5 or 10.0 mM).4. 4. Mitochondria produced significant quantities of 14CO2 when [1,4 14C]succinate was used as substrate, indicating that 14CO2 production from glutamine does not originate solely from the decarboxylation of [alpha] KG.5. 5. Thus chronic acidosis and pH, per se, affect intramitochondrial glutamine carbon skeleton metabolism in different fashions, but the specific mechanism cannot be elucidated using 14CO2 production from [U-14C]glutamine.6. 6. Additional studies directly quantitating the metabolic products of glutamine have confirmed these findings and more precisely defined the sites of metabolic alteration.