tailieunhanh - Báo cáo khoa học: Modular metabolic control analysis of large responses in branched systems – application to aspartate metabolism

Organisms subject to changing environmental conditions or experimental protocols show complex patterns of responses. The design principles behind these patterns are still poorly understood. Here, modular metabolic control analysis is developed to deal with large changes in branched pathways. | IFEBS Journal Modular metabolic control analysis of large responses in branched systems - application to aspartate metabolism Fernando Ortega1 and Luis Acerenza2 1 ComputationalBiology Advanced Science and Technology Laboratory AstraZeneca Macclesfield UK 2 Systems Biology Laboratory Faculty of Sciences University of the Republic Montevideo Uruguay Keywords Asp metabolism large metabolic responses metabolic control analysis metabolic modeling modular analysis Correspondence L. Acerenza Igua 4225 Montevideo 11400 Uruguay Fax 598 2 5258629 Tel 598 2 5258618 E-mail aceren@ Received 17 February 2011 revised 16 April 2011 accepted 17 May 2011 doi Organisms subject to changing environmental conditions or experimental protocols show complex patterns of responses. The design principles behind these patterns are still poorly understood. Here modular metabolic control analysis is developed to deal with large changes in branched pathways. Modular aggregation of the system dramatically reduces the number of explicit variables and modulation sites. Thus the resulting number of control coefficients which describe system responses is small. Three properties determine the pattern for large changes in the variables the values of infinitesimal control coefficients the effect of large rate changes on the control coefficients and the range of rate changes preserving feasible intermediate concentrations. Importantly this pattern gives information about the possibility of obtaining large variable changes by changing parameters inside the module without the need to perform any parameter modulations. The framework is applied to a detailed model of Asp metabolism. The system is aggregated in one supply module producing Thr from Asp SM1 and two demand modules incorporating Thr DM2 and Ile DM3 into protein. Their fluxes are J1 J2 and J3 respectively. The analysis shows similar high infinitesimal control coefficients of J2 by the rates of .

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