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Interrelationships between citrate metabolism, ammoniagenesis, and gluconeogenesis in renal cortex in vitro

  • Sheldon Adler
    Correspondence
    Reprint requests: Dr. Sheldon Adler, Montefiore Hospital, 3459 Fifth Ave., New York, N. Y. 15213.
    Affiliations
    Department of Medicine, University of Pittsburg School of Medicine, and the Montefiore and Presbyterian University Hospitals, Pittsburgh, Pa., USA
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  • Harry G. Preuss
    Affiliations
    Department of Medicine, University of Pittsburg School of Medicine, and the Montefiore and Presbyterian University Hospitals, Pittsburgh, Pa., USA
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      Abstract

      Metabolic acidosis causes an increase in renal cortical citrate decarboxylation, ammonia production, and gluconeogenesis. This study investigated the interrelationships between these 3 variables using a rat renal cortical slice preparation. Slices from control animals incubated in low pH-low bicarbonate media decarboxylated more medium citrate than did slices incubated in alkaline media. In the presence of malonate (20 mM.) this difference completely disappeared. Renal cortical slices obtained from chronically acidotic rats decarboxylated more citrate and produced greater amounts of ammonia and glucose than did slices obtained from alkalotic animals when incubated at an identical medium pH and bicarbonate concentration. When either malonate (20 mM.) or arsenite (1 mM.) was added to the medium, citrate decarboxylation decreased in both groups but remained significantly higher in the acidotic one. Ammonia production decreased somewhat in the acidotic and increased significantly in the alkalotic slices, although differences between groups remain statistically significant. Glucose production, however, was almost totally eliminated in both groups by the inhibitors. It appears that chronic metabolic acidosis affects citrate decarboxylation by 2 methods—1 mediated through the citric acid cycle, and the other unaffected by cycle inhibitors. The latter may correspond to the adaptative increase in ammonia production found in this condition.
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