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

Smallbone, Kieran, Messiha, Hanan L., Carroll, Kathleen M., Winder, Catherine L., Malys, Naglis, Dunn, Warwick B., Murabito, Ettore, Swainston, Neil, Dada, Joseph O., Khan, Farid, Pir, Pınar, Simeonidis, Evangelos, Spasic, Irena ORCID:, Wishart, Jill, Weichart, Dieter, Hayes, Neil W., Jameson, Daniel, Broomhead, David S., Oliver, Stephen G., Gaskell, Simon J., McCarthy, John E. G., Paton, Norman W., Westerhoff, Hans V., Kell, Douglas B. and Mendes, Pedro 2013. A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes. FEBS Letters 587 (17) , pp. 2832-2841. 10.1016/j.febslet.2013.06.043

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Computer Science & Informatics
Subjects: Q Science > QA Mathematics
Uncontrolled Keywords: Glycolysis; Systems biology; Enzyme kinetic; Isoenzyme; Modelling
Publisher: Elsevier
ISSN: 0014-5793
Funders: BBSRC BB/C008219/1, EPSRC
Last Modified: 24 Oct 2022 11:40

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