Pathways of glutamine and organic acid metabolism in renal cortex in chronic metabolic acidosis

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Abstract

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. 15NH3 formation and 15N-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 14CO2 and glucose-14C than did slices from alkalotic animals when labeled glutamine, citrate, or malate was used as substrate but 14CO2 production from pyruvate-1-14C was slightly reduced in acidotic tissue. With most of the substrates used glucose-14C formation was small compared with 14CO2 formation. Using the amount of glucose-14C formed, the expected 14CO2 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 14CO2 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.

Authors

David P. Simpson