ATP turnover and renal response of dog tubules to pH changes in vitro.
In vivo the dog kidney responds to metabolic or respiratory acidosis by a marked increment of its ammonia production (expressed per 100 milliliters glomerular filtration rate). This phenomenon is related to a switch from metabolic utilization of nonammoniagenic (lactate) to ammoniagenic (glutamine) substrates to support ATP turnover in the proximal tubules. We have proposed that in vivo the maximum activity of the ammoniagenic process is fixed by the ATP turnover in this segment of the nephron. The maximal glutamine metabolism is reached when 100% of this turnover is supported by glutamine metabolism. We have studied how these concepts apply to the adaptation of glutamine metabolism and ammonia production to a low pH in vitro using proximal tubules of dogs incubated when one (lactate or glutamine) or several (glutamine plus lactate or plus palmitate) substrates are provided. At pH 7.4 glutamine alone supports already 71-76% of the tissue ATP turnover (minimal and maximal values). With acidification this fraction rises to nearly 87-94%, but this increases only modestly the ammonia production. Reducing the ATP turnover with ouabain at pH 7.4 decreases the absolute glutamine utilization, which now supports only 45-50% of the ATP turnover. Again acidification increases this fraction to 90-99%. Addition of lactate with glutamine displaces part of the glutamine metabolized, but greatly stimulates the synthesis of alanine. Fatty acids depress ammonia production and blunt the tissue response to acidification. Gluconeogenesis from lactate is minimally influenced by incubation pH. It is concluded that the ATP turnover limits the metabolism of glutamine by proximal tubules in vitro as in vivo in the dog, and that the response to acidification is small in vitro because of the absence of alternative substrates.
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D003470:Culture Media; D004285:Dogs; D004734:Energy Metabolism; D005973:Glutamine / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism / Q000502:physiology*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D010101:Oxygen Consumption / Q000187:drug effects; D012709:Serum Albumin / Q000494:pharmacology
D003470:Culture Media; D007773:Lactates; D012709:Serum Albumin; D005973:Glutamine; D019344:Lactic Acid; D000641:Ammonia; D006859:Hydrogen; D000255:Adenosine Triphosphate