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Control theory of metabolic channelling

  • Metabolic Regulation: Theoretical Basis
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Abstract

Various factors appear to control muscle energetics, often in conjunction. This calls for a quantitative approach of the type provided by Metabolic Control Analysis for intermediary metabolism and mitochondrial oxidative phosphorylation. To the extent that direct transfer of high energy phosphates and spatial organization plays a role in muscle energetics however, the standard Metabolic Control Theory does not apply, neither do its theorems regarding control.

This chapter develops the Control Theory that does apply to the muscle system. It shows that direct transfer of high energy phosphates bestows a system with enhanced control: the sum of the control exerted by the participating enzymes on the flux of free energy form the mitochondrial matrix to the actinomyosin may well exceed the 100% mandatory for ideal metabolic pathways. It is also shown how sequestration of high energy phosphates may allow for negative control on pathway flux. The new control theory gives methods functionally to diagnose the extent to which channelling and metabolite sequestration occur.

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Authors and Affiliations

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

    Boris N. Kholodenko

  2. Department de Bioquimica i Fisiologia, Universitat de Barcelona, Marti i Franques 1, Barcelona, Spain

    Marta Cascante

  3. E.C. Slater Institute, University of Amsterdam, Plantage Muidergracht 12, NL-1066 CX, The Netherlands

    Hans V. Westerhoff

  4. Department of Molecular Biology, H5, The Netherlands Cancer Institute, Plesmanlaan 121, NL-1066 CX, The Netherlands

    Hans V. Westerhoff

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  1. Boris N. Kholodenko
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  2. Marta Cascante
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  3. Hans V. Westerhoff
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Kholodenko, B.N., Cascante, M. & Westerhoff, H.V. Control theory of metabolic channelling. Mol Cell Biochem 133, 313–331 (1994). https://doi.org/10.1007/BF01267963

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