Use of labeling pattern of liver glutamate to calculate rates of citric acid cycle and gluconeogenesis.

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  • Author(s): Large V;Large V; Brunengraber H; Odeon M; Beylot M
  • Source:
    The American journal of physiology [Am J Physiol] 1997 Jan; Vol. 272 (1 Pt 1), pp. E51-8.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 0370511 Publication Model: Print Cited Medium: Print ISSN: 0002-9513 (Print) Linking ISSN: 00029513 NLM ISO Abbreviation: Am J Physiol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Physiological Society
      Original Publication: Washington [etc.] American Physiological Society.
    • Subject Terms:
      Citric Acid Cycle* ; Gluconeogenesis*/drug effects; Glutamic Acid/*metabolism ; Liver/*metabolism; Animals ; Dichloroacetic Acid/pharmacology ; Enzyme Inhibitors/pharmacology ; Glucagon/pharmacology ; Lactic Acid/pharmacology ; Methods ; Osmolar Concentration ; Picolinic Acids/pharmacology ; Pyruvate Kinase/metabolism ; Pyruvic Acid/pharmacology ; Rats
    • Abstract:
      The use of the labeling pattern of hepatic glutamate during infusion of L-[3-13C]- or [3-14C]lactate to calculate rates of citric acid cycle activity and gluconeogenesis has been proposed. We tested the validity of this approach by perfusing isolated rat livers (48 h starved) with pyruvate and lactate (10% enriched with [3-13C]lactate) without (control) or with infusion of glucagon (to inhibit pyruvate kinase), mercaptopicolinate (to inhibit phosphoenolpyruvate carboxykinase), or dichloroacetate (to stimulate pyruvate dehydrogenase). Compared with control experiments, glucagon increased glucose output (P < 0.05) and decreased the calculated flux through pyruvate kinase (P < 0.05). Mercaptopicolinate almost totally suppressed glucose production and dramatically reduced the calculated gluconeogenic rate and flux through phosphoenolpyruvate carboxykinase (P < 0.001). Dichloroacetate moderately increased the calculated flux through pyruvate dehydrogenase (P < 0.05). In experiments with perfused livers from fed rats, the calculated gluconeogenic rate and flux through phosphoenolpyruvate carboxykinase were very low compared with control experiments (P < 0.001), whereas the pyruvate dehydrogenase flux was increased (P < 0.05). Therefore, the expected modifications of the citric acid cycle activity and gluconeogenic rate were clearly detected using the labeling pattern of glutamate to calculate these metabolic rates. Except for the perfusions with mercaptopicolinate, the dilution by isotopic exchange in the oxaloacetate pool calculated from the model agreed with the actual dilution of enrichment between liver pyruvate and phosphoenolpyruvate. The present results support the validity of this approach to trace liver metabolism.
    • Grant Information:
      DK-35543 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Enzyme Inhibitors)
      0 (Picolinic Acids)
      33X04XA5AT (Lactic Acid)
      3KX376GY7L (Glutamic Acid)
      7XW1R5R974 (3-mercaptopicolinic acid)
      8558G7RUTR (Pyruvic Acid)
      9007-92-5 (Glucagon)
      9LSH52S3LQ (Dichloroacetic Acid)
      EC 2.7.1.40 (Pyruvate Kinase)
    • Publication Date:
      Date Created: 19970101 Date Completed: 19970328 Latest Revision: 20171213
    • Publication Date:
      20221213
    • Accession Number:
      10.1152/ajpendo.1997.272.1.E51
    • Accession Number:
      9038851