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Dicarboxylic acid fluxes during gluconeogenesis. No channelling of mitochondrial oxalacetate

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Abstract

A rather complete model of the gluconeogenic pathway was used, with the known separate pools of mitochondrial and cytosolic oxalacetate, malate and aspartate. The fumarase, malate dehydrogenase and glutamate oxalacetate transaminase reactions were assumed to be isotopically actively reversible, but none at isotopic equilibrium. Malate was assumed to exchange actively between the mitochondrial and cytosol, while aspartate exchange was more limited, in agreement with the known electrogenic nature of aspartate export from the mitochondria. This model was fit to14C data obtained in hepatocyte studies, and to the whole rat14C data obtained by Heath and Rose (Biochem J. 227, 851–876, 1985). The latter data were easily fit to our model, when a single mitochondrial oxalacetate pool was assumed. However, invoking two mitochondrial oxalacetate pools, as proposed by Heath and Rose, with the oxalacetate formed via pyruvate carboxylase preferentially channelled to gluconeogenesis, could not be fit with the known differences in scrambling in glucose and glutamate produced from L[3-14C]lactate.

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References

  • Baranyai, J. M. and J. J. Blum. 1989. Quantitative analysis of intermediary metabolism in rat hepatocytes incubated in the presence and absence of ethanol with a substrate mixture including ketoleucine.Biochem. J. 258, 121–140.

    Google Scholar 

  • Burch, H. B., O. H. Lowry, A. M. Kuhlman, J. Skerjance, E. J. Diamant, S. R. Lowry and P. von Dieppe. 1963. Changes in patterns of enzymes of carbohydrate metabolism in the developing rat liver.B. biol. Chem. 238, 2267–2273.

    Google Scholar 

  • Clegg, J. S. 1984. Properties and metabolism of the aqueous cytoplasm and its boundaries.Am. J. Physiol. 246, R133-R151.

    Google Scholar 

  • Cohen, S. 1987a.13C NMR study of effects of fasting and diabetes on the metabolism of pyruvate in the tricarboxylic acid cycle and of the utilization of pyruvate and ethanol in lipogenesis in perfused rat liver.Biochemistry 26, 581–589.

    Article  Google Scholar 

  • Cohen, S. 1987b.13C and31P NMR study of gluconeogenesis: utilization of13C-labeled substrates by perfused liver from streptozotocin-diabetic and untreated rats.Biochemistry,26, 563–572.

    Article  Google Scholar 

  • de Haan, E. J. and A. B. Oestreicher. 1968. Abstr. FEBS 5th Meeting, Prague, p. 52.

  • Di Donata, L., C. Des Rosiers, J. A. Montgomery, F. David, M. Garneau and H. Brunengraber. 1993. Rates of gluconeogenesis and citric acid cycle in perfused livers, assessed from the mass spectrometric assay of the13C labelling pattern of glutamate.J. biol. Chem. 268, 4170–4180.

    Google Scholar 

  • Esenmo, E., V. Chandramouli, W. C. Schumann, K. Kumaran, J. Wahren and B. R. Landau. 1992. Use of14CO2 in estimating rates of hepatic gluconeogenesis.Am. J. Physiol. 262, E36-E41.

    Google Scholar 

  • Freedman, A. D. and S. Graff. 1958. The metabolism of pyruvate in the tricarboxylic acid cycle.J. biol. Chem. 233, 292–295.

    Google Scholar 

  • Grunnet, N. and J. Katz, 1978. Effects of ammonia and norvaline on lactate metabolism by hepatocytes from starved rats. The use of14C-labelled lactate in studies of hepatic gluconeogenesis.Biochem. J. 172, 595–603.

    Google Scholar 

  • Heath, D. F. and J. G. Rose. 1985. [14C]Bicarbonate fixation into glucose and other metabolites in the liver of the starved rat under halothane anaesthesia. Metabolic channelling of mitochondrial oxaloacetate.Biochem. J. 227, 851–876.

    Google Scholar 

  • Hetenyi, G. 1982. Corrections for the metabolic exchange of14C for12C-atoms in the pathways of gluconeogenesisin vivo.Fed. Proc. 41, 104–109.

    Google Scholar 

  • Katz, J. 1985. Determination of gluconeogenesis in vivo with14C-labeled substrates.Am. J. Physiol. 248, R391-R399.

    Google Scholar 

  • Kelleher, J. 1986. Gluconeogenesis from labeled carbon; estimating isotope dilution.Am. J. Physiol. 250, E296-E305.

    Google Scholar 

  • Koeppe, R. E., G. A. Mourkides and R. J. Hill. Some factors affecting routes of pyruvate metabolism in rats.J. biol. Chem. 234, 2219–2222.

  • Landau, B. R., G. E. Bartsch, J. Katz and H. G. Wood. 1964. Estimation of pathway contributions to glucose metabolism and of the rate of isomerization of hexose-6-phosphate.J. biol. Chem. 239, 686–696.

    Google Scholar 

  • La Noue, K. F., A. J. Meijer and A. Brower, 1974. Evidence for electrogenic aspartate transport in rat liver mitochondria.Arch. Biochem. Biophys. 161, 544–550.

    Article  Google Scholar 

  • Lardy, H. A., V. Paetkau and P. Walter. 1965. Paths of carbon in gluconeogenesis and lipogenesis; the role of mitochondria in supplying precursors of phosphoenol-pyruvate.Proc. Natl. Acad. Sci. U.S.A. 53, 1410–1415.

    Article  Google Scholar 

  • Magnusson, I., W. C. Schumann, G. E. Bartsch, V. Chandramouli, K. Kumaran, J. Wahren and B. R. Landau, 1991. Noninvasive tracing of Krebs cycle metabolism in liver.J. Biol. Chem. 266, 5975–5984.

    Google Scholar 

  • Rognstad, R. 1980. [14C]Distribution in glucose formed from pyruvate in rat hepatocytes.Int. J. Biochem. 13, 509–510.

    Article  Google Scholar 

  • Rognstad, R. 1981. Manganese effects on gluconeogenesis.J. biol. Chem. 256, 1608–1610.

    Google Scholar 

  • Rognstad, R. 1982.14CO2 fixation by phosphoenolpyruvate carboxykinase during gluconeogenesis in the intact rat liver cell.J. biol. Chem. 257, 11486–11488.

    Google Scholar 

  • Rognstad, R. 1988. Gluconeogenesis in vivo. Correction factors for interaction with the Krebs cycle.Med. Sci. Res. 16, 293–294.

    Google Scholar 

  • Rognstad, R. 1991. Evidence against tight channelling of NADH in hepatocytes.Arch. Biochem. Biophys. 286, 555–561.

    Article  Google Scholar 

  • Rognstad, R. 1992. Complete stepwise degradation of glutamic acid.Biochem. Arch. 8, 215–219.

    Google Scholar 

  • Rognstad, R. 1993. Difficulties in the use of14C models for the estimation of gluconeogenesisin vivo.Biochem. Arch. 9, 15–25.

    Google Scholar 

  • Rognstad, R. and J. Katz. 1970. Gluconeogenesis in the kidney cortex. Effects of D-malate and aminooxyacetate.Biochem. J. 116, 483–491.

    Google Scholar 

  • Rognstad, R. and J. Katz. 1973. Malate exchange between the cytosol and mitochondria.Biochem. J. 132, 349–352.

    Google Scholar 

  • Rognstad, R., D. G. Clark and J. Katz. 1974. Glucose synthesis in tritiated water.Eur. J. Biochem. 47, 383–388.

    Article  Google Scholar 

  • Rognstad, R., P. Wals and J. Katz. 1975. Metabolism of [5T]fructose by isolated liver cells.J. biol. Chem. 250, 8642–8646.

    Google Scholar 

  • Rose, I. A., R. Kellemeyer, R. Stjerholm and H. G. Wood. 1962. The distribution of14C in glycogen from deuterated glycerol-14C as a measure of the effectiveness of triosephosphate isomerasein vivo.J. biol. Chem. 237, 3325–3331.

    Google Scholar 

  • Schmidt, K., J. Genovese and J. Katz. 1970. Enzymic degradation of isotopically labelled compounds II. Glucose labelled with14C and tritium.Analyt. Biochem. 34, 170–179.

    Article  Google Scholar 

  • Spivey, H. O. and J. M. Merz. 1989. Metabolic compartmentation.BioEssays 10, 127–130.

    Article  Google Scholar 

  • Strisower, E. F., G. D. Kohler and I. L. Chaikoff. 1952. Incorporation of acetate carbon into glycose by liver slices from normal and alloxan-diabetic rats.J. biol. Chem. 198, 115–126.

    Google Scholar 

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  1. Whittier Diabetes Program, Department of Medicine, University of California, San Diego, 92093-0983, La Jolla, CA, U.S.A.

    Robert Rognstad

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  1. Robert Rognstad
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Rognstad, R. Dicarboxylic acid fluxes during gluconeogenesis. No channelling of mitochondrial oxalacetate. Bltn Mathcal Biology 57, 557–568 (1995). https://doi.org/10.1007/BF02460783

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  • DOI: https://doi.org/10.1007/BF02460783

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