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Metabolic control analysis to identify optimal drug targets

  • Chapter
Systems Biological Approaches in Infectious Diseases

Part of the book series: Progress in Drug Research ((PDR,volume 64))

Abstract

This chapter describes the basic principles of Metabolic Control Analysis (MCA) which is a quantitative methodology to evaluate the importance and relative contribution of individual metabolic steps in the overall functioning of a particular system. The control on the flux through a metabolic pathway or subsystem can be quantified by the control coefficients of the individual enzymes or components which reflects the extent to which the component is rate-limiting. The perturbation of an individual step is measured by its elasticity coefficient. The effect of perturbation of a single step on the entire pathway or subsystemis, in turn, measured by the response coefficient. Differential control analysis can be used to compare flux through a single metabolic pathway in a pathogen with the same pathway in its host to identify uniquely vulnerable steps with the greatest potential for specifically inhibiting flux through the pathogen metabolic pathway. The utility of this methodology is illustrated with the glycolysis in Trypanosomes and with oncogenic signaling.

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Author information

Authors and Affiliations

  1. Department of Molecular Cell Physiology, Institute for Molecular Cell Biology, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, The Netherlands

    Jorrit J. Hornberg, Frank J. Bruggeman, Barbara M. Bakker & Hans V. Westerhoff

  2. Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary BioCentre, Faculty of Engineering and Physical Sciences, University of Manchester, Manchester, UK

    Frank J. Bruggeman & Hans V. Westerhoff

  3. Department of Mathematical Biochemistry, University of Amsterdam, Amsterdam, The Netherlands

    Hans V. Westerhoff

  4. Molecular Parmacology Unit, NV Organon, Oss, The Netherlands

    Jorrit J. Hornberg

Authors
  1. Jorrit J. Hornberg
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  2. Frank J. Bruggeman
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  3. Barbara M. Bakker
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  4. Hans V. Westerhoff
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Editor information

Editors and Affiliations

  1. Tuberculosis Research Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20852, USA

    Helena I. Boshoff  & Clifton E. Barry III  & 

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Hornberg, J.J., Bruggeman, F.J., Bakker, B.M., Westerhoff, H.V. (2007). Metabolic control analysis to identify optimal drug targets. In: Boshoff, H.I., Barry, C.E. (eds) Systems Biological Approaches in Infectious Diseases. Progress in Drug Research, vol 64. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7567-6_7

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