Regulation of Glutamine Metabolism In Vitro by Bicarbonate Ion and pH

A B S TRA CT The effect of variations of medium pH and bicarbonate concentration on glutamine oxidation was studied in slices and mitochondria from dog renal cortex. Decreasing pH and bicarbonate concentration increased the rate of oxidation of glutamine-U-14C to 4CO2 in both slices and mitochondria, an effect com-parable to the acute stimulation of glutamine utilization produced by metabolic acidosis. Decreases in the con-centration of glutamate and a-ketoglutarate, which ac-company metabolic acidosis in the intact animal, also occurred in tissue slices when pH and [HC03-] were lowered; decrease in a-ketoglutarate but not in gluta-mate content occurred in mitochondria under these conditions. Study of independent variations of medium pH and [HCO,-] showed that simultaneous changes in both pH and [HCO3-] produced a greater effect on glu-tamine metabolism than did change in either of these parameters alone. The rate of glutamine oxidation was also compared in tissue preparations from pairs of litter-mate dogs with chronic metabolic acidosis and alkalosis. No sig-nificant difference in the rate of glutamine oxidation was present in mitochondria from the two sets of animals. Slices from animals with chronic metabolic acidosis consistently oxidized glutamine at a more rapid rate than slices from alkalotic dogs both at high and at low concentrations of bicarbonate in the medium. We be-lieve this difference is a result of the same mechanism which leads to the delayed increase in ammonium ex-cretion during induction of metabolic acidosis. The close parallel between the effects demonstrated here and the changes in ammonium production and glu-tamine utilization in the intact animal with metabolic acidosis suggest that the observed in vitro changes ac-This work was presented in part at a meeting of th