Renal metabolite concentrations and the activities of glutaminase and glutamate dehydrogenase during recovery from metabolic acidosis in the rat.
Metabolite content was determined in freeze-clamped kidneys to elucidate the rate-controlling steps which are responsible for the inhibition of renal ammoniagenesis that occurs when rats are allowed to recover from metabolic acidosis. After 1 day of recovery from acidosis there were increased renal contents of glutamate, glutamine, alpha-ketoglutarate, citrate, lactate, and malate. The calculated cytoplasmic concentration of oxaloacetate was also increased. The renal content of phosphoenolpyruvate, 3-phosphoglycerate, and ammonia decreased during recovery. No changes were observed in the renal content of the adenine nucleotides or of inorganic phosphate. The activities of phosphate-dependent glutaminase and glutamate dehydrogenase were elevated even after 7 days of recovery although the renal contents of glutamate and alpha-ketoglutarate had returned to control levels by this time. The changes in oxaloacetate and phosphoenolpyruvate are consistent with the fall in the activity of phosphoenolpyruvate carboxykinase observed by Parry and Brosnan. The increased levels of alpha-ketoglutarate and of glutamate are considered to be a consequence of a primary change in the activity of alpha-ketoglutarate dehydrogenase. These results are discussed in the light of the known effects of these metabolites on glutaminase activity and on glutamine entry into renal mitochondria.
D000138:Acidosis / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D005943:Gluconeogenesis; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010071:Oxaloacetates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D000596:Amino Acids; D010071:Oxaloacetates; D000641:Ammonia; D005969:Glutamate Dehydrogenase; D005972:Glutaminase