Journal of Bioenergetics and Biomembranes

, Volume 27, Issue 5, pp 479–490 | Cite as

Metabolic regulation: A control analytic perspective

  • Jan-Hendrik S. Hofmeyr


A possible basis for a quantitative theory of metabolic regulation is outlined. Regulation is defined here as the alteration of reaction properties to augment or counteract the mass-action trend in a network reactions. In living systems the enzymes that catalyze these reactions are the “handles” through which such alteration is effected. It is shown how the elasticity coefficients of an enzyme-catalyzed reaction with respect to substrates and products are the sum of a massaction term and a regulatory kinetic term; these coefficients therefore distinguish between massaction effects and regulatory effects and are recognized as the key to quantifying regulation. As elasticity coefficients are also basic ingredients of metabolic control analysis, it is possible to relate regulation to such concepts as control, signalling, stability, and homeostasis. The need for care in the choice of relative or absolute changes when considering questions of metabolic regulation is stressed. Although the concepts are illustrated in terms of a simple coupled reaction system, they apply equally to more complex systems. When such systems are divided into reaction blocks, co-response coefficients can be used to measure the elasticities of these blocks.

Key words

Metabolic regulation metabolic control analysis signals homeostasis co-response analysis 


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  1. Atkinson, D. E. (1977).Cellular Energy Metabolism and Its Regulation, Academic Press, New York.Google Scholar
  2. Brown, G. C. (1993). InModern Trends in BioThermoKinetics (Schuster, S., Rigoulet, M., Ouhabi, R., and Mazat, J.-P, eds.), Plenum Press, New York, pp. 461–489.Google Scholar
  3. Brown, G. C., Hafner, R. P., and Brand, M. D. (1990).Eur. J. Biochem. 188, 321–325.CrossRefPubMedGoogle Scholar
  4. Burns, J. A., Cornish-Bowden, A., Groen, A. K., Heinrich, R., Kacser, H., Porteous, J. W., Rapoport, S. M., Rapoport, T. A., Stucki, J. W., Tager, J. M., Wanders, R. J. A., and Westerhoff, H. V. (1985).Trends Biochem. Sci. 10, 16.CrossRefGoogle Scholar
  5. Chance, B. (1961).Cold Spring Harbor Symp. Quant. Biol. 26, 289–299.Google Scholar
  6. Chen, Y.-D., and Westerhoff, H. V. (1986).Math. Model. 7, 1173–1180.CrossRefGoogle Scholar
  7. Cornish-Bowden, A. (1981).Basic Mathematics for Biochemists. Chapman and Hall, London.Google Scholar
  8. Cornish-Bowden, A. (1995).Adv. Mol. Cell. Biol. 11, 21–64.Google Scholar
  9. Cornish-Bowden, A., and Hofmeyr, J.-H. S. (1991).Comp. Appl. Biosci. 7, 89–93.PubMedGoogle Scholar
  10. Cornish-Bowden, A., and Hofmeyr, J.-H. S. (1994).Biochem. J. 298, 367–375.PubMedGoogle Scholar
  11. Dawkins, R. (1986).The Blind Watchmaker, W. W. Norton, New York.Google Scholar
  12. Fell, D. A. (1992).Biochem. J. 286, 313–330.PubMedGoogle Scholar
  13. Heinrich, R., and Rapoport, T. A. (1974).Eur. J. Biochem. 42, 89–95.CrossRefPubMedGoogle Scholar
  14. Heinrich, R., Rapoport, S. M., and Rapoport, T. A. (1977).Prog. Biophys. Mol. Biol. 32, 1–82.CrossRefPubMedGoogle Scholar
  15. Higgins, J. (1967).Ind. Eng. Chem. 59, 19–62.CrossRefGoogle Scholar
  16. Hofmeyr, J.-H. S., and Cornish-Bowden, A. (1991).Eur. J. Biochem. 200, 223–236.CrossRefPubMedGoogle Scholar
  17. Hofmeyr, J.-H. S., Cornish-Bowden, A., and Rohwer, J. M. (1993).Eur. J. Biochem. 212, 833–837.CrossRefPubMedGoogle Scholar
  18. Jacob, F. (1983). InEvolution from Molecules to Men (Rondall, D., ed.), Cambridge University Press, Cambridge.Google Scholar
  19. Kacser, H., and Burns, J. A. (1973).Symp. Soc. Exp. Biol. 32, 65–104.Google Scholar
  20. Kauffman, S. A. (1993).The Origins of Order: Self-Organisation and Selection in Evolution, Oxford University Press, New York.Google Scholar
  21. Melendez-Hevia, E., Waddell, T. G., and Montero, F. (1994).J. Theor. Biol. 166, 201–220.CrossRefGoogle Scholar
  22. Monod, J., Wyman, J., and Changeux, J.-P. (1965).J. Mol. Biol. 12, 88–118.PubMedGoogle Scholar
  23. Nicolis, G., and Prigogine, I. (1977).Self-Organization in Non-Equilibrium Systems, Wiley, New York.Google Scholar
  24. Popova, S. V., and Sel'kov, E. E. (1975).FEBS Lett. 53, 269–273.CrossRefPubMedGoogle Scholar
  25. Popova, S. V., and Sel'kov, E. E. (1978).Mol. Biol. (Moskva) 13, 129–139.Google Scholar
  26. Reich, J. G., and Sel'kov, E. E. (1981).Energy Metabolism of the Cell, Academic Press, London.Google Scholar
  27. Schuster, S., and Heinrich, R. (1992).BioSystems 27, 1–15.CrossRefPubMedGoogle Scholar
  28. Stadtman, E. R. (1970). InThe Enzymes (Boyer, P., ed.), 3rd edn, Vol. 1, Academic Press, New York, pp. 397–459.Google Scholar
  29. Tyson, J. J. (1975).J. Chem. Phys. 62, 1010–1015.CrossRefGoogle Scholar
  30. Westerhoff, H. V., and van Dam, K. (1987).Thermodynamics and Control of Free-Energy Transduction, Elsevier, Amsterdam.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Jan-Hendrik S. Hofmeyr
    • 1
  1. 1.Department of BiochemistryUniversity of StellenboschStellenboschSouth Africa

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