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‘Why do tumour cells glycolyse?’: From glycolysis through citrate to lipogenesis

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Abstract

The re-emergence of interest in intermediary metabolism and the development of metabolomics in relation to cancer and other diseases provide a timely reason to revisit issues of tumour cell metabolism. In this review, we address the issue of the role of high aerobic glycolysis, which is commonly associated with the metabolism of many tumour cells. The concept presented emphasises the importance of the glycolysis-citrate-lipogenesis pathway in providing the synthetic and bioenergetic requirements that are essential for the growth and proliferation of tumour cells. We hope that our discussion will be informative and instructive, and will stimulate interest and research regarding the intermediary metabolism and its regulation in tumour cells. We express our appreciation to the many pioneering and contemporary researchers whose studies provide much of the basis for this presentation. (Mol Cell Biochem xxx: 1–8, 2005)

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References

  1. Racker E, Spector M: Warburg effect revisited: merger of biochemistry and molecular biology. Science 213: 303–307, 1981

    PubMed  CAS  Google Scholar 

  2. Warburg O, Wind F, Negelein E: Uber den Stoffwechsel von Tumouren im Korper. Klin Woch 5: 829–832, 1926

    CAS  Google Scholar 

  3. Chance B, Hess B: Spectroscopic evidence of metabolic control. Science 129: 700–708, 1959

    PubMed  CAS  Google Scholar 

  4. Dang CV, Samenza, GL: Oncogenic alterations of metabolism. Trends Bio Sci 24: 68–72, 1999

    CAS  Google Scholar 

  5. Baggetto, LG: Deviant energetic metabolism of glycolytic cancer cells. Biochimie 74: 959–974, 1992

    Google Scholar 

  6. Menendez JA, Colomer R, Lupu R: Why does tumour-associated fatty acid synthase (oncogenic antigen-519) ignore dietary fatty acids? Med Hypoth 64: 342–3499, 2005

    Google Scholar 

  7. Argiles JM, Lopez-Soriano FJ: Way do cells have such a high glycolytic rate. Med Hypoth 32: 151–155, 1990

    Article  CAS  Google Scholar 

  8. Parlo RA, Coleman PS: Enhanced rate of citrate export from cholesterol-rich hepatoma mitochondria. J Biol Chem 259: 997–10003, 1984

    Google Scholar 

  9. Pedersen, PL: Tumour mitochondria and the bioenergetics of cancer cells. Prog Exp Tumour Res 22: 190–274, 1978

    CAS  Google Scholar 

  10. Modica-Napolitano JS, Singh KK: Mitochondrial dysfunction in cancer. Mitochondrion 4: 755–762, 2004

    Article  PubMed  CAS  Google Scholar 

  11. Matsuno T: Bioenergetics of tumour cells: glutamine metabolism in tumour cell mitochondria. Int J Biochem 19(4): 303–307, 1987

    Article  PubMed  CAS  Google Scholar 

  12. Sauer LA, Stayman JW 3rd, Dauchy RT: Amino acid, glucose, and lactic acid utilization in vivo by rat tumours. Cancer Res 42: 4090–4097, 1982

    PubMed  CAS  Google Scholar 

  13. McKeechan WL: Glycolysis, glutaminolysis and cell proliferation. Cell Biol Int Rep 6: 635–650, 1982

    Google Scholar 

  14. Franklin RB, Costello LC: Glutamate dehydrogenase in rat ventral prostate and a proposed aspartate-glutamate pathway of citrate synthesis. J Urol 132: 1239–1243, 1984

    PubMed  CAS  Google Scholar 

  15. Costello LC, Franklin RB: Prostate epithelial cells utilize glucose and aspartate as the carbon sources for net citrate production. Prostate 15: 335–342, 1989

    PubMed  CAS  Google Scholar 

  16. Costello LC, Liu Y, Franklin RB, Kennedy MC: Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem 272: 28875–28881, 1997

    Article  PubMed  CAS  Google Scholar 

  17. Costello LC, Franklin RB: The intermediary metabolism of the prostate: a key to understanding the pathogenesis and progression of prostate malignancy. Oncology 59: 269–282, 2001

    Google Scholar 

  18. Costello LC, Franklin RB: The novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate 35: 285–296, 1998

    Article  PubMed  CAS  Google Scholar 

  19. Parlo RA, Coleman PS: Continuous pyruvate carbon flux to newly synthesized cholesterol and the suppressed evolution of pyruvate-generated CO2 in tumours: further evidence for a persistent truncated Krebs cycle in hepatomas. Biochim Biophys Acta 886: 169–176, 1986

    PubMed  CAS  Google Scholar 

  20. Reitzer LJ, Wice BM, Kennell D: Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J Biol Chem 254: 2669–2775, 1979

    PubMed  CAS  Google Scholar 

  21. Dietzen DJ, Davis EJ: Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria. Arch Biochem Biophys. 305: 91–102, 1993

    Article  PubMed  CAS  Google Scholar 

  22. Hernanz A, de la Fuente M: Characterization of aconitate hydratase from mitochondria and cytoplasm of ascites tumour cells. Biochem Cell Biol 66: 792–795, 1988

    Article  PubMed  CAS  Google Scholar 

  23. Costello LC, Franklin RB: Concepts of citrate production and secretion by prostate. 1. Metabolic relationships. Prostate 18: 25–46, 1991

    PubMed  CAS  Google Scholar 

  24. Franklin RB, Costello LC, Littleton G: Citrate uptake and oxidation by fragments of rat ventral prostate. Enzyme 22: 45–51, 1977

    PubMed  CAS  Google Scholar 

  25. Moreadith RW, Lehninger AL: The pathways of glutamate and glutamine oxidation by tumour cell mitochondria. Role of mitochondrial NAD(P)+-dependent malic enzyme. J Biol Chem 259: 6215–6221, 1984

    PubMed  CAS  Google Scholar 

  26. Loikkanen I, Haghighi S, Vainio S, Pajunen A: Expression of cytosolic acetyl-CoA synthetase gene is developmentally regulated. Mech Dev 115: 139–141, 2002

    Article  PubMed  CAS  Google Scholar 

  27. Sone H, Shimano H, Sakakura Y, Inoue N, Amemiya-Kudo M, Yahagi N, Osawa M, Suzuki H, Yokoo T, Takahashi A, Iida K, Toyoshima H, Iwama A, Yamada N: Acetyl-coenzyme A synthetase is a lipogenic enzyme controlled by SREBP-1 and energy status. Am J Physiol Endocrinol Metab 282: E222–230, 2002

    PubMed  CAS  Google Scholar 

  28. Oikawa E, Iijima H, Suzuki T, Sasano H, Sato H, Kamataki A, Nagura H, Kang MJ, Fujino T, Suzuki H, Yamamoto TT: A novel acyl-CoA synthetase, ACS5, expressed in intestinal epithelial cells and proliferating preadipocytes. J Biochem (Tokyo) 124: 679–685, 1998

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Sciences, Dental School/University of Maryland, Baltimore, Maryland

    Leslie C. Costello & Renty B. Franklin

  2. Department of Biomedical Sciences, Dental School/University of Maryland, 666 West Baltimore Street, Baltimore, Maryland, 21201

    Leslie C. Costello

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  1. Leslie C. Costello
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  2. Renty B. Franklin
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Costello, L.C., Franklin, R.B. ‘Why do tumour cells glycolyse?’: From glycolysis through citrate to lipogenesis. Mol Cell Biochem 280, 1–8 (2005). https://doi.org/10.1007/s11010-005-8841-8

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  • DOI: https://doi.org/10.1007/s11010-005-8841-8

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