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Molecular and Cellular Biochemistry

, Volume 5, Issue 1–2, pp 17–23 | Cite as

History of the Pasteur effect and its pathobiology

  • Efraim Racker
Article

Summary

Long before the mechanism of fermentation was understood,Pasteur discovered an important regulatory phenomenon of carbohydrate metabolism. He observed that yeast consumes more sugar anaerobically than aerobically. This so-called Pasteur effect has been subject of many controversies and an analysis of the development of the concepts has been presented. Among the key errors made in the early evaluations was to emphasize the control of end product formation rather than of hexose utilization.

The Pasteur phenomenon as understood at present is a complex coordinated control mechanism which operates at several levels. The basic phenomenon is a competition between glycolysis and oxidative phosphorylation for the available ADP and inorganic phosphate. Superimposed are allosteric controls of hexokinase (glucose-6-phosphate) and of phosphofructokinase (ATP). However, in some cells glucose-6-phosphate is not an inhibitor of hexokinase and ATP levels do not change significantly during transition from aerobic to anaerobic conditions. It is therefore clear that other secondary allosteric effectors such as inorganic phosphate play a significant role. The major conclusion is that there are multiple and different control mechanisms participating in the Pasteur effect in different cells.

A loss of control in tumor cells gives rise to a high aerobic glycolysis. The history and possible significance of this in malignancy is described.

Keywords

Control Mechanism Oxidative Phosphorylation Hexose Carbohydrate Metabolism Hexokinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    L. Pasteur, C. R. Acad. Sci. 52, 1260–1264 (1861).Google Scholar
  2. 2.
    O. Warburg, Biochem. Z. 172, 432–441 (1926).Google Scholar
  3. 3.
    D. Burk, Cold Spring Harb. Symp. quant. Biol. 7, 420–459 (1939).Google Scholar
  4. 4.
    H. A. Krebs, in Essays in Biochemistry (P. N. Campbell and F. Dickens, eds.) Academic Press. Vol. 8, p. 1–34 (1972).Google Scholar
  5. 5.
    J. Fruton, “Molecules and Life”, John Wiley & Sons, Inc. New York (1972).Google Scholar
  6. 6.
    F. Kützing, J. Prakt. Chem. 11, 385–409 (1837).Google Scholar
  7. 7.
    L. Pasteur, Comp. Rend. 45, 913–916 (1857).Google Scholar
  8. 8.
    F. Lynen, Justus Liebigs Ann. Chem. 546, 120–141 (1941).Google Scholar
  9. 9.
    M. Johnson, Science, 94, 200–202 (1941).Google Scholar
  10. 10.
    R. Wu and E. Racker, J. Biol. Chem. 234, 1029–1035 (1959).Google Scholar
  11. 11.
    B. Chance, in Ciba Foundation Symposium on the Regulation of Cell Metabolism (G. E. W. Wolstenholme and C. M. O'Conner, eds.), J. & A. Churchill, London, pp. 91–121 (1959).Google Scholar
  12. 12.
    J. B. Alpers, R. Wu and E. Racker, J. Biol. Chem. 238, 2274–2280 (1963).Google Scholar
  13. 13.
    E. C. Dodds and G. D. Greville, Lancet I, 398–399 (1934).Google Scholar
  14. 14.
    W. F. Loomis and F. Lipmann, J. Biol. Chem. 173, 807–808 (1948).Google Scholar
  15. 15.
    S. Gatt and E. Racker, J. Biol. Chem. 234, 1024–1028 (1959).Google Scholar
  16. 16.
    E. Racker in Advances in Enzymology (F. F. Nord, ed.), Interscience Publishers, New York, Vol. XV, pp. 141–182 (1954).Google Scholar
  17. 17.
    F. Lynen and R. Königsberger, Justus Liebigs Ann. Chem. 573, 60 (1951).Google Scholar
  18. 18.
    V. A. Engelhardt and N. E. Sakov, Biokhimiya, 8, 9–36 (1943).Google Scholar
  19. 19.
    F. Lynen, G. Hartmann, K. F. Netter and A. Schuegraf, in Ciba Foundation Symposium on the Regulation of Cell Metabolism (G. E. W. Wolstenholme and C. M. O'Conner, eds.) J. & A. Churchill, London, pp. 256–237 (1959).Google Scholar
  20. 20.
    K. K. Lonberg-Holm, Biochim. Biophys. Acta, 35, 464–472 (1959).Google Scholar
  21. 21.
    H. A. Lardy and R. E. Parks, Jr., in Enzymes: Units of Biological Structure and Function (O. H. Gaebler, ed.), Academic Press, New York, p. 584 (1956).Google Scholar
  22. 22.
    K. Uyeda and E. Racker, J. Biol. Chem. 240, 4689–4693 (1965).Google Scholar
  23. 23.
    J. R. Williams, B. A. Herczeg, H. S. Coles and W. Y. Cheung, J. Biol. Chem. 242, 5119–5124 (1967).Google Scholar
  24. 24.
    E. Racker, “Mechanisms in Bioenergetics”, Academic Press, Inc., New York (1965).Google Scholar
  25. 25.
    J. V. Passonneau and O. H. Lowry, Biochim. Biophys. Res. Commun. 7, 10–15 (1962).Google Scholar
  26. 26.
    K. Uyeda and E. Racker, J. Biol. Chem. 240, 4682–4688 (1965).Google Scholar
  27. 27.
    I. A. Rose, J. V. B. Warms and O'Connel, E. L., Biochem. Biophys. Res. Commun. 15, 33 (1964).Google Scholar
  28. 28.
    J. Krzanowski and F. M. Matschinsky, Biochem. Biophys. Res. Commun. 34, 816–823 (1969).Google Scholar
  29. 29.
    P. J. Randle, R. M. Denton and P. J. England, in The Metabolic Roles of Citrate (T. W. Goodwin, ed.) Biochemical Society Symposium, 27, pp. 87–103 (1968).Google Scholar
  30. 30.
    Z. Dische, Bull. Soc. Chim. Biol. 23, 1140–1148 (1941).Google Scholar
  31. 31.
    S. Rapoport, personal communication.Google Scholar
  32. 32.
    R. Wu and E. Racker, J. Biol. Chem. 234, 1036–1041 (1959).Google Scholar
  33. 33.
    E. B. Goldberg, H. M. Nitowsky and S. P. Colowick, J. Biol. Chem. 240, 2791 (1965).Google Scholar
  34. 34.
    K. Tornheim and J. M. Lowenstein, J. Biol. Chem., 248, 2670–2677 (1973).Google Scholar
  35. 35.
    G. Acs, T. Garzo, G. Grosz, J. Molnar, O. Stephaneck, and F. B. Straub, Acta Physiol. Acad. Sci., Hung. 8, 269 (1955).Google Scholar
  36. 36.
    I. A. Rose and J. V. B. Warms, J. Biol. Chem. 242, 1635–1645 (1967).Google Scholar
  37. 37.
    H. R. Knull, W. J. Taylor and W. W. Wells, J. Biol. Chem. 248, 5414–5418 (1973).Google Scholar
  38. 38.
    O. Warburg, Über den Stoffwechsel der Tumoren, Springer Verlag, Berlin (1926).Google Scholar
  39. 39.
    C. F. Cori and G. T. Cori, J. Biol. Chem. 65, 397 (1925).Google Scholar
  40. 40.
    C. E. Wenner, in Advances in Enzymology (F. F. Nord, ed.), Interscience Publishers, New York, Vol. 29, pp. 321–390 (1967).Google Scholar
  41. 41.
    E. Racker, American Scientist, 60, 56–63 (1972).Google Scholar
  42. 42.
    S. Weinhouse, Science, 124, 267 (1956).Google Scholar
  43. 43.
    E. Racker, R. Wu and J. B. Alpers, in Amino Acids, Proteins and Cancer Biochemistry (J. T. Edsall, ed.) Academic Press, New York, pp. 175–189 (1960).Google Scholar
  44. 44.
    P. Scholnick, D. Lang and E. Racker, J. Biol. Chem. 248, 5175–5182 (1973).Google Scholar
  45. 45.
    P. Mitchell, Biol. Rev. (Cambridge) 41, 445 (1966).Google Scholar
  46. 46.
    E. Racker, Biochim. Biophys. Acta, in press (1973).Google Scholar
  47. 47.
    E. P. Wigner, Proc. Am. Phil. Soc. 133, 95–101 (1969).Google Scholar
  48. 48.
    M. Polanyi, Science, 160, 1308–1312 (1968).Google Scholar

Copyright information

© Dr. W. Junk b.v. Publishers 1974

Authors and Affiliations

  • Efraim Racker
    • 1
  1. 1.Section of BiochemistryMolecular & Cell Biology Cornell UniversityIthacaUSA

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