tailieunhanh - Báo cáo khoa học: An extension to the metabolic control theory taking into account correlations between enzyme concentrations

The classical metabolic control theory [Kacser, H. & Burns, . (1973). 27, 65–104; Heinrich, R. & Rapoport, T. (1974)Eur. J. , 89–95.] does not take into account experimental evidence for correlations between enzyme concentrations in the cell. We investigated the implications of two causes of linear correlations: competition between enzymes, which is a mere physical adaptation of the cell to the limitation of resources and space, and regulatory correlations, which result from the existence of regulatory networks | Eur. J. Biochem. 271 4375-4391 2004 FEBS 2004 doi An extension to the metabolic control theory taking into account correlations between enzyme concentrations Sébastien Lion 1 Frederic Gabriel1 Bruno Bost2 Julie Fievet1 Christine Dillmann1 and Dominique de Vienne1 1UMR de Génétique Végétale INRAịUPSịCNRSỊINAPG Ferme du Moulon Gif-sur-Yvette France 2Institut de Génétique et Microbiologie CNRS UMR 8621 Universite Paris Sud Orsay Cedex France The classical metabolic control theory Kacser H. Burns . 1973 Symp. Soc. Exp. Biol. 27 65-104 Heinrich R. Rapoport T. 1974 Eur. J. Biochem. 42 89-95. does not take into account experimental evidence for correlations between enzyme concentrations in the cell. We investigated the implications of two causes of linear correlations competition between enzymes which is a mere physical adaptation of the cell to the limitation of resources and space and regulatory correlations which result from the existence of regulatory networks. These correlations generate redistribution of enzyme concentrations when the concentration of an enzyme varies this may dramatically alter the flux and metabolite concentration curves. In particular negative correlations cause the flux to have a maximum value for a defined distribution of enzyme concentrations. Redistribution coefficients of enzyme concentrations allowed us to calculate the combined response coefficient that quantifies the response of flux or metabolite concentration to a perturbation of enzyme concentration. Keywords biochemical modelling cellular constraint flux metabolite response coefficient. The introduction of the metabolic control theory by Kacser Burns 1 and Heinrich Rapoport 2 was a great improvement in our understanding of the control of metabolism for a review see 3 . Numerous extensions to the classical theory have been proposed to get rid of some restrictive hypotheses of the initial theory. Extensions exist for example for nonproportionality of