Pathways of glutamine and organic acid metabolism in renal cortex in chronic metabolic acidosis.
The metabolism of labeled glutamine and of several labeled organic acid anions was compared in tissue slices of renal cortex from chronically acidotic and alkalotic littermate dogs. (15)NH(3) formation and (15)N-amideglutamine utilization were significantly increased by slices from acidotic animals providing further evidence for the similarity of the metabolic responses seen in the tissue slice system and the physiologic effects produced by chronic metabolic acidosis on renal metabolism in the intact animal. Slices from acidotic dogs formed more (14)CO(2) and glucose-(14)C than did slices from alkalotic animals when labeled glutamine, citrate, or malate was used as substrate but (14)CO(2) production from pyruvate-1-(14)C was slightly reduced in acidotic tissue. With most of the substrates used glucose-(14)C formation was small compared with (14)CO(2) formation. Using the amount of glucose-(14)C formed, the expected (14)CO(2) production was calculated based on the hypothesis that the primary site of action of metabolic acidosis is on a cytoplasmic step in gluconeogenesis. The actual difference in (14)CO(2) production between slices from acidotic and alkalotic animals always greatly exceeded this predicted amount, indicating that stimulation of gluconeogenesis represents a minor metabolic response to chronic metabolic acidosis. Evidence from experiments with citrate labeled in various positions showed that metabolic acidosis has its principal effect on an early step in substrate metabolism which must be intramitochondrial in location.
D000138:Acidosis / Q000378:metabolism*; D000641:Ammonia / Q000096:biosynthesis; D000818:Animals; D001345:Autoradiography; D002245:Carbon Dioxide / Q000096:biosynthesis; D002247:Carbon Isotopes; D002951:Citrates / Q000378:metabolism; D046508:Culture Techniques; D004285:Dogs; D005947:Glucose / Q000096:biosynthesis; D005973:Glutamine / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D009587:Nitrogen Isotopes; D011773:Pyruvates / Q000378:metabolism
D002247:Carbon Isotopes; D002951:Citrates; D008293:Malates; D009587:Nitrogen Isotopes; D011773:Pyruvates; D005973:Glutamine; D002245:Carbon Dioxide; D000641:Ammonia; D005947:Glucose