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How constrained is metabolic control?

L Acerenza1

  • 1Sección Biofisica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. aceren@fcien.edu.uy

Journal of Theoretical Biology
|October 7, 1996
PubMed
Summary
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Metabolic control is highly constrained, with few independent control coefficients due to structural and kinetic limitations. This limited metabolic regulation is primarily caused by kinetic constraints, not evolutionary pressure for simpler systems.

Area of Science:

  • Biochemistry
  • Systems Biology
  • Metabolic Engineering

Background:

  • Metabolic control is quantified by control coefficients, which describe responses to rate changes.
  • Metabolic pathways exhibit structural and kinetic constraints, limiting the independence of these coefficients.

Purpose of the Study:

  • To define and evaluate the degree of constraint in metabolic control.
  • To introduce metrics: fraction of independent control coefficients (fw) and independent coefficients per variable [N(C/V)].

Main Methods:

  • Expressing fw using fractions of independent metabolite concentrations, fluxes, and metabolite effects on rates.
  • Defining N(C/V) as the average number of metabolites influencing each rate.

Main Results:

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  • A small fraction of control coefficients are independent in cellular metabolism.
  • The average number of rates independently controlling each variable is significantly below its theoretical maximum.
  • Kinetic constraints are identified as the primary driver for low fw and N(C/V) values.

Conclusions:

  • Cellular metabolic control is inherently constrained.
  • Kinetic factors, rather than evolutionary optimization for simplicity, explain the observed constraints.
  • Organisms do not evolve towards less constrained metabolic responses due to these fundamental limitations.