Ketone body effects on glutamine metabolism in isolated kidneys and mitochondria

L. Goldstein, R. J. Solomon, D. F. Perlman, P. M. McLaughlin and M. A. Taylor beta-Hydroxybutyrate (but not acetoacetate) caused marked inhibition of ammonia production and glutamine extraction in isolated perfused kidneys from normal rats. Glutamine synthesis was not affected by beta-hydroxybutyrate (BHB). Measurement of metabolite levels in freeze-clamped kidneys showed that BHB increased glutamine concentration, decreased ammonia concentration, and reduced the mitochondrial NAD+/NADH ratio (calculated) in perfused kidneys. BHB inhibited flux through the glutamate dehydrogenase pathway, probably as a result of reduction in the NAD+/NADH ratio, in isolated renal mitochondria. In isolated perfused kidneys from acidotic rats, ammonia production and mitochondrial NAD+/NADH were both elevated and BHB did not inhibit renal ammoniagenesis. Although ammonia production in the acidotic kidneys was not directly related to the mitochondrial NAD+/NADH ratio, the elevation of this ratio may have permitted a normal rate of oxidation of glutamine end products--which is essential for maintaining the elevated ammoniagenesis--to take place in the presence of BHB.