Metabolism of glutamine and glutamic acid by isolated perfused kidneys of normal and acidotic rats.
1. When isolated kidneys from fed rats were perfused with glutamine the rate of ammonia release at pH7.4 (110-360mumol/h per g dry wt.) was one to two times that of glutamine removal. Glucose formation from 5mm-glutamine was 16mumol/h per g. If kidneys were perfused with glutamine at pH7.1 (10-13mm-sodium bicarbonate) there was no increase in glutamine removal or in the formation of ammonia or glucose. 2. When isolated kidneys from fed rats were perfused with glutamate at pH7.4, glucose formation was 59mumol/h per g, glutamine formation was 182mumol/h per g and ammonia release was negligible. At pH7.1 glutamine synthesis was inhibited and formation of ammonia and glucose were increased. 3. In perfused kidneys from acidotic rats, which had received 1.5% (w/v) NH(4)Cl to drink for 7-10 days, gluconeogenesis from glutamine was enhanced (101mumol/h per g). Glutamine removal and ammonia formation were also increased, compared with the rates in perfused kidney from normal rats. The extra glutamine consumed was equivalent to the extra glucose formed. 4. When the kidney from the 7-10-day-acidotic rat was perfused with glutamate gluconeogenesis was increased (113mumol/h per g). Synthesis of glutamine was decreased, and ammonia release was approximately equal to the rate of glutamate removal. 5. The time-course of these metabolic alterations was investigated after the rapid induction of acidosis by infusion of 0.25m-HCl into the right side of the heart. The increase in gluconeogenesis from glutamine developed gradually over several hours. When kidneys from 6h-acidotic rats were perfused with glutamate, formation of glucose and glutamine were both rapid. 6. In acidotic rat kidneys perfused with glutamine, tissue concentrations of glutamate and glucose 6-phosphate were increased compared with those in control perfused kidneys from non-acidotic rats. 7. The results are discussed in terms of control of the renal metabolism of glutamine. In particular, it is suggested that in acidotic rats glucose formation is the major fate of the carbon of the extra glutamine utilized by the kidney, and that inhibition of glutamine synthetase could contribute to the increase in intracellular ammonia concentration in the kidney.
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006321:Heart; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D013217:Starvation
D005971:Glutamates; D007773:Lactates; D005973:Glutamine; D000641:Ammonia; D005974:Glutamate-Ammonia Ligase; D005947:Glucose; D006851:Hydrochloric Acid