Role of the Mitochondrial Anion Transporters in the Regulation of Ammoniagenesis in Renal Cortex Mitochondria of the Rabbit and Rat

Abstract

Factors which may regulate ammoniagenesis in the kidney cortex were studied. Emphasis was placed on the segment of the pathway by which the carbons derived from glutamine must exit from the mitochondrion. These pathways were compared in the rat with high rates of ammoniagenesis, and the rabbit which has a low rate of ammoniagenesis. The dicarboxylate transporter, which is essential for ammoniagenesis, has a maximum velocity which was much lower in the rabbit. The malate concentration required for half-maximal rates of transport was 14 nmol/mg mitochondrial protein and similar in both species. There was no effect of chronic metabolic acidosis on dicarboxylate transporter activity. The tricarboxylate transporter activity with phosphoenol pyruvate as substrate also had a low activity in the rabbit kidney-cortex mitochondria. The maximum velocity of phosphate dependent glutaminase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase were all much greater than the maximal rate of ammoniagenesis observed in vivo in the rabbit. The low rates of ammoniagenesis and the failure to adapt to acidosis in the rabbit are best explained by factors influencing the dicarboxylate transporter.