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

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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 et al.
(2013) A model of yeast glycolysis based on a consistent kinetic characterisation of all its enzymes. FEBS Letters, Volume 587 (Number 17). pp. 2832-2841. doi:10.1016/j.febslet.2013.06.043

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Official URL: http://dx.doi.org/10.1016/j.febslet.2013.06.043

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Abstract

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: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Saccharomyces cerevisiae , Metabolism , Glycolysis , Enzyme kinetics
Journal or Publication Title: FEBS Letters
Publisher: Elsevier BV
ISSN: 0014-5793
Official Date: 2013
Dates:
DateEvent
2013Published
Volume: Volume 587
Number: Number 17
Page Range: pp. 2832-2841
DOI: 10.1016/j.febslet.2013.06.043
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Engineering and Physical Sciences Research Council (EPSRC), University of Manchester. Manchester Centre for Integrative Systems Biology (MCISB) , Seventh Framework Programme (European Commission) (FP7), National Institutes of Health (U.S.) (NIH)
Grant number: BB/C008219/1 (BBSRC/EPSRC) ; 289434 (FP7) ; BB/J019259/1 (BBSRC) ; R01GM080219 (NIH)

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