tailieunhanh - Báo cáo khoa học: Modular metabolic control analysis of large responses The general case for two modules and one linking intermediate

Deciphering the laws that govern metabolic responses of complex systems is essential to understand physiological functioning, pathological conditions and the outcome of experimental manipulations of intact cells. To this aim, a theoretical and experimental sensitivity analysis, called modular meta-bolic control analysis (MMCA), was proposed. | ễFEBS Journal Modular metabolic control analysis of large responses The general case for two modules and one linking intermediate Luis Acerenza1 and Fernando Ortega2 1 Laboratorio de Biologia de Sistemas Facultad de Ciencias Universidad de la Republica Iguếỉ Montevideo Uruguay 2 Schoolof Biosciences The University of Birmingham UK Keywords metabolic control analysis metabolic control design metabolic responses modular control analysis top-down control analysis Correspondence L. Acerenza Laboratorio de Biologia de Sistemas Facultad de Ciencias Universidad de la Republica 4225 Montevideo 11400 Uruguay Fax 598 2 525 8629 Tel 598 2 525 8618-23 Ext. 139 E-mail aceren@ Note Dedicated to the memory of Reinhart Heinrich one of the fathers of Metabolic Control Theory Received 5 October 2006 accepted 7 November 2006 doi Deciphering the laws that govern metabolic responses of complex systems is essential to understand physiological functioning pathological conditions and the outcome of experimental manipulations of intact cells. To this aim a theoretical and experimental sensitivity analysis called modular metabolic control analysis MMCA was proposed. This field was previously developed under the assumptions of infinitesimal changes and or proportionality between parameters and rates which are usually not fulfilled in vivo. Here we develop a general MMCA for two modules not relying on those assumptions. Control coefficients and elasticity coefficients for large changes are defined. These are subject to constraints summation and response theorems and relationships that allow calculating control from elasticity coefficients. We show how to determine the coefficients from topdown experiments measuring the rates of the isolated modules as a function of the linking intermediate there is no need to change parameters inside the modules . The novel formalism is applied to data of two experimental studies from the literature. In one of .

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