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Related Experiment Videos

Defining control coefficients in non-ideal metabolic pathways.

B N Kholodenko1, D Molenaar, S Schuster

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

Biophysical Chemistry
|November 1, 1995
PubMed
Summary

The traditional definition of enzyme control over metabolic flux is ambiguous in complex pathways. New "elemental control coefficients" offer a precise, modulation-independent measure for analyzing metabolic pathway regulation.

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Metabolic Engineering

Background:

  • Traditional metabolic control analysis defines enzyme control by flux modulation.
  • This definition becomes ambiguous in pathways with metabolic channeling or high enzyme concentrations.
  • Conserved moieties involving both enzymatic and non-enzymic species also introduce ambiguity.

Purpose of the Study:

  • To address the ambiguity in defining flux control coefficients in complex metabolic pathways.
  • To introduce a new, unambiguous method for quantifying enzyme control over metabolic flux.
  • To provide a framework for more accurate analysis of metabolic pathway regulation.

Main Methods:

  • Modeling biochemically relevant pathways, including those with dynamic metabolite channeling and moiety-conserved cycles.

Related Experiment Videos

  • Defining and applying 'elemental control coefficients' based on modulation of elemental step rate constants.
  • Developing the concept of 'impact control coefficients' as the sum of elemental control coefficients.

    • Main Results:

    • The traditional flux control coefficient is ambiguous in non-ideal metabolic pathways.
    • Elemental control coefficients provide an unambiguous measure of control, independent of modulation method.
    • Impact control coefficients quantify enzyme activation effects and relate to traditional coefficients in ideal pathways.

    Conclusions:

    • Ambiguity in traditional flux control coefficients arises from pathway non-idealities like channeling.
    • Elemental control coefficients offer a robust and precise alternative for metabolic control analysis.
    • Differences between impact and traditional coefficients highlight pathway non-idealities, guiding further research.