Simeonidis, Vangelis[University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > > ; University of Manchester > Manchester Centre for Integrative Systems Biology]
[en] We present an experimental and computational pipeline for the generation of kinetic models of metabolism, and demonstrate its application to glycolysis in Saccharomyces cerevisiae. Starting from an approximate mathematical model, we employ a ‘‘cycle of knowledge’’ strategy, identifying the steps with most control over flux. Kinetic parameters of the individual isoenzymes within these steps are measured experimentally under a standardised set of conditions. Experimental strategies are applied to establish a set of in vivo concentrations for isoenzymes and metabolites. The data are integrated into a mathematical model that is used to predict a new set of metabolite concentrations and reevaluate the control properties of the system. This bottom-up modelling study reveals that control over the metabolic network most directly involved in yeast glycolysis is more widely distributed than previously thought.
Manchester Centre for Integrative Systems Biology ; Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
BBSRC / EPSRC
The Manchester Centre for Integrative Systems Biology
The final model, as available on the BioModels database. Other version also available form BioModels and from the JWS Online, where they can be simulated online at http://http://jjj.mib.ac.uk/