Ketone body effects on glutamine metabolism in isolated kidneys and mitochondria.
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.
D020155:3-Hydroxybutyric Acid; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D005919:Glomerular Filtration Rate; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000494:pharmacology; D007657:Ketone Bodies / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014554:Urination
D006885:Hydroxybutyrates; D007657:Ketone Bodies; D005973:Glutamine; D009243:NAD; D000641:Ammonia; D005969:Glutamate Dehydrogenase; D020155:3-Hydroxybutyric Acid