tailieunhanh - Báo cáo khoa học: Kinetic hybrid models composed of mechanistic and simplified enzymatic rate laws – a promising method for speeding up the kinetic modelling of complex metabolic networks

Kinetic modelling of complex metabolic networks – a central goal of com-putational systems biology – is currently hampered by the lack of reliable rate equations for the majority of the underlying biochemical reactions and membrane transporters. | Kinetic hybrid models composed of mechanistic and simplified enzymatic rate laws - a promising method for speeding up the kinetic modelling of complex metabolic networks Sascha Bulik1 Sergio Grimbs2 Carola Huthmacher1 Joachim Selbig2 3 and Hermann G. Holzhutter1 1 Institute of Biochemistry Charite - University Medicine Berlin Germany 2 Department of Bioinformatics Max-Planck-Institute for Molecular Plant Physiology Potsdam-Golm Germany 3 Institute of Biochemistry and Biology University of Potsdam Germany Keywords kinetic modelling LinLog metabolic network Michaelis-Menten power law Correspondence S. Bulik University Medicine Berlin -Charite Institute of Biochemistry Monbijoustr. 2 10117 Berlin Germany Fax 49 30 450 528 937 Tel 49 30 450 528 466 E-mail These authors contributed equally to this work Note The mathematical models described here have been submitted to the Online Cellular Systems Modelling Database and can be accessed free of charge at http . database bulik doi Kinetic modelling of complex metabolic networks - a central goal of computational systems biology - is currently hampered by the lack of reliable rate equations for the majority of the underlying biochemical reactions and membrane transporters. On the basis of biochemically substantiated evidence that metabolic control is exerted by a narrow set of key regulatory enzymes we propose here a hybrid modelling approach in which only the central regulatory enzymes are described by detailed mechanistic rate equations and the majority of enzymes are approximated by simplified nonmechanistic rate equations . mass action LinLog Michaelis-Menten and power law capturing only a few basic kinetic features and hence containing only a small number of parameters to be experimentally determined. To check the reliability of this approach we have applied it to two different metabolic networks the energy and redox metabolism of