How do inhibitors and modifiers of individual enzymes affect steady-state fluxes and concentrations in metabolic systems?

Abstract By using metabolic control theory we show how one can calculate the effect on steady-state metabolite concentrations and steady-state fluxes of small amounts of inhibitors or activators of individual enzymes in a metabolic system of arbitrary complexity. It turns out that only limited knowledge of the kinetics of the enzymes in the systems, summarized in their “Elasticity Coefficients,” is needed. An example of an actual calculation is given.

[1]  Reinhart Heinrich,et al.  A Linear Steady-State Treatment of Enzymatic Chains Critique of the Crossover Theorem and a General Procedure to Identify Interaction Sites with an Effector , 1974 .

[2]  I. Verma Oncogenic intelligence: From c-fos to v-fos , 1984, Nature.

[3]  Reinhart Heinrich,et al.  A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. , 1974, European journal of biochemistry.

[4]  A. Cornish-Bowden,et al.  Control analysis of metabolic systems , 1985 .

[5]  M. Savageau Biochemical systems analysis. II. The steady-state solutions for an n-pool system using a power-law approximation. , 1969, Journal of theoretical biology.

[6]  John L. Wyatt,et al.  Network modelling of reaction-diffusion systems and their numerical solution using spice , 1980 .

[7]  H. Kung,et al.  Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein , 1984, Nature.

[8]  R Heinrich,et al.  Metabolic regulation and mathematical models. , 1977, Progress in biophysics and molecular biology.

[9]  J. Bishop Cellular oncogenes and retroviruses. , 1983, Annual review of biochemistry.

[10]  H. Westerhoff,et al.  Modern theories of metabolic control and their applications , 1984, Bioscience reports.

[11]  H. Westerhoff,et al.  Metabolic control and compartmentation in single living cells , 1983, Cell biochemistry and function.

[12]  M A Savageau,et al.  Concepts relating the behavior of biochemical systems to their underlying molecular properties. , 1971, Archives of biochemistry and biophysics.

[13]  H. Westerhoff,et al.  How do enzyme activities control metabolite concentrations? An additional theorem in the theory of metabolic control. , 1984, European journal of biochemistry.

[14]  Eberhard O. Voit,et al.  Power-Law Approach to Modeling Biological Systems : I. Theory , 1982 .