A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes.

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TitleA model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes.
Publication TypeJournal Article
Year of Publication2013
AuthorsSmallbone, K, Messiha, HL, Carroll, KM, Winder, CL, Malys, N, Dunn, WB, Murabito, E, Swainston, N, Dada, JO, Khan, F, Pir, P, Simeonidis, E, Spasić, I, Wishart, J, Weichart, D, Hayes, NW, Jameson, D, Broomhead, DS, Oliver, SG, Gaskell, SJ, McCarthy, JEG, Paton, NW, Westerhoff, HV, Kell, DB, Mendes, P
JournalFEBS Lett
Volume587
Issue17
Pagination2832-41
Date Published2013 Sep 2
ISSN1873-3468
KeywordsComputer Simulation, Glycolysis, Isoenzymes, Kinetics, Metabolic Networks and Pathways, Models, Biological, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Systems Biology
Abstract

<p>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.</p>

DOI10.1016/j.febslet.2013.06.043
Alternate JournalFEBS Lett.
PubMed ID23831062
PubMed Central IDPMC3764422
Grant ListBB/E024181/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 GM080219 / GM / NIGMS NIH HHS / United States
BB/C008219/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/J019259/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom