tailieunhanh - Báo cáo khoa học: Something from nothing ) bridging the gap between constraint-based and kinetic modelling

Two divergent modelling methodologies have been adopted to increase our understanding of metabolism and its regulation. Constraint-based modelling highlights the optimal path through a stoichiometric network within certain physicochemical constraints. | ễFEBS Journal Something from nothing - bridging the gap between constraint-based and kinetic modelling Kieran Smallbone1 2 Evangelos Simeonidis1 3 David S. Broomhead1 2 and Douglas B. Kell1 4 1 Manchester Centre for Integrative Systems Biology The University of Manchester UK 2 Schoolof Mathematics The University of Manchester UK 3 Schoolof ChemicalEngineering and AnalyticalScience The University of Manchester UK 4 Schoolof Chemistry The University of Manchester UK Keywords flux balance analysis linlog kinetics Saccharomyces cerevisiae Correspondence K. Smallbone Manchester Centre for Integrative Systems Biology Manchester Interdisciplinary Biocentre 131 Princess Street Manchester M1 7 DN UK Fax 44 161 30 65201 Tel 44 161 30 65146 E-mail Website http Received 29 June 2007 revised 17 August 2007 accepted 29 August 2007 doi Two divergent modelling methodologies have been adopted to increase our understanding of metabolism and its regulation. Constraint-based modelling highlights the optimal path through a stoichiometric network within certain physicochemical constraints. Such an approach requires minimal biological data to make quantitative inferences about network behaviour however constraint-based modelling is unable to give an insight into cellular substrate concentrations. In contrast kinetic modelling aims to characterize fully the mechanics of each enzymatic reaction. This approach suffers because parameterizing mechanistic models is both costly and time-consuming. In this paper we outline a method for developing a kinetic model for a metabolic network based solely on the knowledge of reaction stoichiometries. Fluxes through the system estimated by flux balance analysis are allowed to vary dynamically according to linlog kinetics. Elasticities are estimated from stoichiometric considerations. When compared to a popular branched model of yeast glycolysis we observe an excellent .