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. 1987 Oct 1;247(1):47–51. doi: 10.1042/bj2470047

Interaction of metabolism of aspartate and inosine and energy state of malignant cells.

Z Kovacević 1, J Popović 1, O Brkljac 1, S Lelas 1
PMCID: PMC1148367  PMID: 3689353

Abstract

1. Oxidation of glutamine in Ehrlich ascites-carcinoma cells results in a large accumulation of aspartate. 2.The addition of inosine causes a marked decrease in aspartate production from glutamine. This may be related to the resynthesis of AMP from aspartate and IMP, the latter being produced from inosine via the salvage pathway for purine nucleotides. In accordance with this assumption, a significant production of lactate was observed, which comes probably from the ribose moiety of inosine. Since lactate is known to inhibit production of aspartate from glutamine, this may explain the effect of inosine. 3. Addition of glutamine together with inosine increased cellular ATP content. This was not the case if glutamine or inosine was present separately or if inosine was added together with lactate, pyruvate or glucose. The effect did not occur if amino-oxyacetate, an inhibitor of transaminases, was added. These findings suggested again that production of aspartate is important for resynthesis of ATP from IMP via the purine nucleotide cycle. 4.If the cells were exposed to prolonged anaerobic incubation, addition of glutamine and inosine markedly increased O2 uptake and [ATP], suggesting the crucial importance of aspartate production by glutamine oxidation for the recovery of energy metabolism in the cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bush L. R., Warren S., Mesh C. L., Lucchesi B. R. Comparative effects of aspartate and glutamate during myocardial ischemia. Pharmacology. 1981;23(6):297–304. doi: 10.1159/000137565. [DOI] [PubMed] [Google Scholar]
  2. HEINZ E., LOEWE U., DESPOPOULOS A., PFEIFFER B. TRANSPORT AND METABOLISM OF GLUTAMATE IN EHRLICH ASCITES CARCINOMA CELLS. Biochem Z. 1964 Nov 6;340:487–502. [PubMed] [Google Scholar]
  3. Hoek J. B., Njogu R. M. The role of glutamate transport in the regulation of the pathway of proline oxidation in rat liver mitochondria. J Biol Chem. 1980 Sep 25;255(18):8711–8718. [PubMed] [Google Scholar]
  4. Kirsch W. M., Schulz Q., Van Buskirk J., Nakane P. Anaerobic energy metabolism in brain tumors. Prog Exp Tumor Res. 1972;17:163–191. doi: 10.1159/000393673. [DOI] [PubMed] [Google Scholar]
  5. Kovacevic Z., McGivan J. D. Mitochondrial metabolism of glutamine and glutamate and its physiological significance. Physiol Rev. 1983 Apr;63(2):547–605. doi: 10.1152/physrev.1983.63.2.547. [DOI] [PubMed] [Google Scholar]
  6. Kovacević Z., Morris H. P. The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res. 1972 Feb;32(2):326–333. [PubMed] [Google Scholar]
  7. Kovacević Z. Possibility for the transfer of reducing equivalents from the cytosol to the mitochondrial compartment in Ehrlich ascites tumor cells by the malate-aspartate shuttle. Eur J Biochem. 1972 Feb 15;25(2):372–378. doi: 10.1111/j.1432-1033.1972.tb01706.x. [DOI] [PubMed] [Google Scholar]
  8. Kovacević Z. The pathway of glutamine and glutamate oxidation in isolated mitochondria from mammalian cells. Biochem J. 1971 Dec;125(3):757–763. doi: 10.1042/bj1250757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krebs H. A., Lund P. Aspects of the regulation of the metabolism of branched-chain amino acids. Adv Enzyme Regul. 1976;15:375–394. doi: 10.1016/0065-2571(77)90026-7. [DOI] [PubMed] [Google Scholar]
  10. Lowenstein J. M. Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev. 1972 Apr;52(2):382–414. doi: 10.1152/physrev.1972.52.2.382. [DOI] [PubMed] [Google Scholar]
  11. Lund P. Glutamine metabolism in the rat. FEBS Lett. 1980 Aug 25;117 (Suppl):K86–K92. doi: 10.1016/0014-5793(80)80573-4. [DOI] [PubMed] [Google Scholar]
  12. Moreadith R. W., Lehninger A. L. The pathways of glutamate and glutamine oxidation by tumor cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme. J Biol Chem. 1984 May 25;259(10):6215–6221. [PubMed] [Google Scholar]
  13. Newsholme E. A., Crabtree B., Ardawi M. S. The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep. 1985 May;5(5):393–400. doi: 10.1007/BF01116556. [DOI] [PubMed] [Google Scholar]
  14. Sauer L. A., Dauchy R. T., Nagel W. O., Morris H. P. Mitochondrial malic enzymes. Mitochondrial NAD(P)+-dependent malic enzyme activity and malate-dependent pyruvate formation are progression-linked in Morris hepatomas. J Biol Chem. 1980 May 10;255(9):3844–3848. [PubMed] [Google Scholar]
  15. Watford M., Vinay P., Lemieux G., Gougoux A. The regulation of glucose and pyruvate formation from glutamine and citric-acid-cycle intermediates in the kidney cortex of rats, dogs, rabbits and guinea pigs. Biochem J. 1980 Jun 15;188(3):741–748. doi: 10.1042/bj1880741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Weber G. Biochemical strategy of cancer cells and the design of chemotherapy: G. H. A. Clowes Memorial Lecture. Cancer Res. 1983 Aug;43(8):3466–3492. [PubMed] [Google Scholar]
  17. Weber G., Prajda N., Jackson R. C. Key enzymes of IMP metabolism: transformation and proliferation-linked alterations in gene expression. Adv Enzyme Regul. 1976;14:3–24. doi: 10.1016/0065-2571(76)90005-4. [DOI] [PubMed] [Google Scholar]
  18. Windmueller H. G., Spaeth A. E. Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate. J Biol Chem. 1980 Jan 10;255(1):107–112. [PubMed] [Google Scholar]
  19. Zielke H. R., Sumbilla C. M., Sevdalian D. A., Hawkins R. L., Ozand P. T. Lactate: a major product of glutamine metabolism by human diploid fibroblasts. J Cell Physiol. 1980 Sep;104(3):433–441. doi: 10.1002/jcp.1041040316. [DOI] [PubMed] [Google Scholar]

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