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Kinetic constraints on the sensitivity of large metabolic responses
© Ortega and Acerenza; licensee BioMed Central Ltd. 2007
Published: 8 May 2007
The quantitative study of metabolic responses in intact cells is essential for predicting the phenotypic consequences of genetic manipulations. Metabolic responses have been described within the framework of metabolic control analysis (MCA) . One of the central goals of MCA is to determine how the responses of system variables, quantified by control coefficients, depend on the kinetic properties of the component reactions or groups of reactions (modules). Attempts to extend infinitesimal control analysis to large changes in the variables have been reviewed in previous publications [2, 3].
In the present contribution, we analyse how some kinetic features of the modules constraint the sensitivity of large metabolic responses. In particular, we explore the different kinds of flux control profile that can be achieved using modules that follow two different types of rate equations: Michaelis-Menten (M-M) and Hill.
Materials and methods
The mean control coefficient quantifies the sensitivity of a steady-state metabolic variable (W) to changes in a parameter (p). It is defined as . It represents the relative change in W divided by the relative change in p when the system goes from one initial (o) to one final steady state (x) .
We have analysed two different models to see if certain patterns of control for large changes could be, in principle, obtained using modules whose rates are governed by usual rate equations. We have shown that, if the rates of both modules obey hyperbolic kinetics, the flux control distribution is constrained, one module having the greatest control over all enzyme activity range. On the contrary, if the rate of the demand module follows a Hill kinetics, which module has the greatest control on the flux depends on the enzymatic activity change.
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