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Subtleties in control by metabolic channelling and enzyme organization

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Bioenergetics of the Cell: Quantitative Aspects

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 25))

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Abstract

Because of its importance to cell function, the free-energy metabolism of the living cell is subtly and homeostatically controlled. Metabolic control analysis enables a quantitative determination of what controls the relevant fluxes. However, the original metabolic control analysis was developed for idealized metabolic systems, which were assumed to lack enzyme-enzyme association and direct metabolite transfer between enzymes (channelling). We here review the recently developed molecular control analysis, which makes it possible to study non-ideal (channelled, organized) systems quantitatively in terms of what controls the fluxes, concentrations, and transit times. We show that in real, non-ideal pathways, the central control laws, such as the summation theorem for flux control, are richer than in ideal systems: the sum of the control of the enzymes participating in a non-ideal pathway may well exceed one (the number expected in the ideal pathways), but may also drop to values below one. Precise expressions indicate how total control is determined by non-ideal phenomena such as ternary complex formation (two enzymes, one metabolite), and enzyme sequestration. The bacterial phosphotransferase system (PTS), which catalyses the uptake and concomitant phosphorylation of glucose (and also regulates catabolite repression) is analyzed as an experimental example of a non-ideal pathway. Here, the phosphoryl group is channelled between enzymes, which could increase the sum of the enzyme control coefficients to two, whereas the formation of ternary complexes could decrease the sum of the enzyme control coefficients to below one. Experimental studies have recently confirmed this identification, as well as theoretically predicted values for the total control. Macromolecular crowding was shown to be a major candidate for the factor that modulates the non-ideal behaviour of the PTS pathway and the sum of the enzyme control coefficients. (Mol Cell Biochem 184: 311–320, 1998)

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Author information

Authors and Affiliations

  1. A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119899, Moscow, Russia

    Boris N. Kholodenko

  2. Departmento de Bioquímica i Biología Molecular, Universitat de Barcelona, Martí i Franqués 1, E-08028, Barcelona, Spain

    Boris N. Kholodenko & Marta Cascante

  3. E.C. Slater Institute, BioCentrum, University of Amsterdam, Plantage Muidergracht 12, NL-1018 TV, Amsterdam, The Netherlands

    Johann M. Rohwer & Hans V. Westerhoff

  4. Department of Microbial Physiology, BioCentrum, Faculty of Biology, Free University, De Boelelaan 1087, NL-1081, HV Amsterdam, The Netherlands

    Hans V. Westerhoff

Authors
  1. Boris N. Kholodenko
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  2. Johann M. Rohwer
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  3. Marta Cascante
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  4. Hans V. Westerhoff
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Editor information

Editors and Affiliations

  1. Laboratories of Bioenergetics, Institute of Chemical and Biological Physics, Tallinn, Estonia

    Valdur A. Saks

  2. Cellular and Molecular Cardiology, U 446 INSERM, Chatenay-Malabry, France

    Renée Ventura-Clapier

  3. Laboratory of Bioenergetics, Joseph Fourier University, Grenoble, France

    Valdur A. Saks , Xavier Leverve  & André Rossi ,  & 

  4. Laboratory of Bioenergetics, Institute of Biochemistry and Cellular Genetics CNRS, Bordeaux, France

    Michel Rigoulet

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© 1998 Springer Science+Business Media Dordrecht

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Kholodenko, B.N., Rohwer, J.M., Cascante, M., Westerhoff, H.V. (1998). Subtleties in control by metabolic channelling and enzyme organization. In: Saks, V.A., Ventura-Clapier, R., Leverve, X., Rossi, A., Rigoulet, M. (eds) Bioenergetics of the Cell: Quantitative Aspects. Developments in Molecular and Cellular Biochemistry, vol 25. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5653-4_20

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  • DOI: https://doi.org/10.1007/978-1-4615-5653-4_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7587-6

  • Online ISBN: 978-1-4615-5653-4

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