tailieunhanh - Báo cáo khoa học:The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks

Cellular functions are ultimately linked to metabolic fluxes brought about by thousands of chemical reactions and transport processes. The synthesisof theunderlying enzymes and membrane transporters causes the cell a certain effort of energyandexternal that those cells should have had a selection advantage during natural evo-lution that enabled them to fulfil vital functions (such as growth, defence against toxic compounds, repair of DNA alterations, etc.) | Eur. J. Biochem. 271 2905-2922 2004 FEBS 2004 doi The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks Hermann-Georg Holzhiitter Humboldt-University Berlin Medical School Charite Institute of Biochemistry Berlin Germany Cellular functions are ultimately linked to metabolic fluxes brought about by thousands of chemical reactions and transport processes. The synthesis of the underlying enzymes and membrane transporters causes the cell a certain effort of energy and external resources. Considering that those cells should have had a selection advantage during natural evolution that enabled them to fulfil vital functions such as growth defence against toxic compounds repair of DNA alterations etc. with minimal effort one may postulate the principle of flux minimization as follows given the available external substrates and given a set of functionally important target fluxes required to accomplish a specific pattern of cellular functions the stationary metabolic fluxes have to become a minimum. To convert this principle into a mathematical method enabling the prediction of stationary metabolic fluxes the total flux in the network is measured by a weighted linear combination of all individual fluxes whereby the thermodynamic equilibrium constants are used as weighting factors . the more the thermodynamic equilibrium lies on the right-hand side of the reaction the larger the weighting factor for the backward reaction. A linear programming technique is applied to minimize the total flux at fixed values of the target fluxes and under the constraint of flux balance steady-state conditions with respect to all metabolites. The theoretical concept is applied to two metabolic schemes the energy and redox metabolism of erythrocytes and the central metabolism of Methylobac-terium extorquens AM1. The flux rates predicted by the fluxminimization method exhibit significant correlations with flux