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Why and when channelling can decrease pool size at constant net flux in a simple dynamic channel

P Mendes1, D B Kell, H V Westerhoff

  • 1Institute of Biological Sciences, University of Wales, Aberystwyth, UK.

Biochimica Et Biophysica Acta
|March 15, 1996
PubMed
Summary
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Metabolic channeling can decrease intermediate metabolite concentrations, even at constant pathway flux. This study refutes claims that such effects are artifacts, demonstrating channeling

Area of Science:

  • Biochemistry
  • Metabolic Engineering
  • Systems Biology

Background:

  • Previous simulations suggested metabolic channeling can reduce intermediate pool sizes while increasing pathway flux.
  • Cornish-Bowden and Cárdenas contested these findings, proposing they were artifacts of minor flux changes or inappropriate enzyme alterations.

Purpose of the Study:

  • To investigate the co-response of intermediate metabolite concentration (pool) and channel flux to kinetic or thermodynamic parameter changes.
  • To analytically and numerically demonstrate whether metabolic channeling can decrease intermediate pool sizes at constant total flux.

Main Methods:

  • Analytical proofs and numerical simulations were employed.
  • Analysis involved examining the co-response of metabolite concentration and channel flux to parameter variations.

Related Experiment Videos

  • Specific attention was given to relaxing constraints imposed in previous analyses.

    • Main Results:

    • The co-response between intermediate metabolite concentration and channel flux can be positive, negative, or null, depending on the parameter change.
    • It was proven that intermediate metabolite concentration can decrease with increasing channel flux, irrespective of total flux variation.
    • Metabolic channeling was shown to significantly modulate pool size even at constant total flux, challenging prior assertions.

    Conclusions:

    • The assertion that channeling cannot affect intermediate concentration at constant flux is incorrect.
    • Metabolic channeling is a viable mechanism for reducing intermediate metabolite pools, even under conditions of constant pathway flux.
    • The co-response of metabolite concentration and channel flux to parameter changes is generally non-zero and significant.