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Control of metabolic pathways by time-scale separation

J Delgado1, J C Liao

  • 1Department of Chemical Engineering, Texas A & M University, College Station 77843-3122, USA.

Bio Systems
|January 1, 1995
PubMed
Summary

Metabolic control is localized to a few enzymes using time-scale separation. Overproducing most enzymes allows control over a few, simplifying metabolic modeling and control coefficient determination.

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Area of Science:

  • Biochemistry
  • Systems Biology
  • Enzyme Kinetics

Background:

  • The distribution of metabolic control is not fully understood, despite intuitive explanations.
  • Analyzing control coefficients in complex biological systems remains a challenge.

Purpose of the Study:

  • To investigate the underlying principles of metabolic control distribution.
  • To identify strategies for localizing metabolic control to specific enzymes.

Main Methods:

  • Application of control coefficient properties to systems with time-scale separation (widely separated Jacobian eigenvalues).
  • Analysis of 'fast' versus 'slow' reactions based on enzyme overproduction and expression levels.
  • Theoretical derivation under assumptions of stable steady-state and linear kinetics.

Main Results:

  • Time-scale separation effectively localizes metabolic control to a few enzymes.
  • Overproducing enzymes creates 'fast' reactions with small control coefficients for metabolite concentrations.
  • 'Fast' reactions have limited control over overall flux but can influence branch point fluxes.

Conclusions:

  • Time-scale separation provides a framework for understanding metabolic control localization.
  • Results justify simplifying 'fast' reactions in mathematical models and experimental analyses.
  • Strategies for enzyme overproduction can be employed to manage metabolic control.

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