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Enzyme characterisation and kinetic modelling of the pentose phosphate pathway in yeast

, , , , , ,
1 Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom
2 Manchester Center for Integrative Systems Biology, The University of Manchester, Manchester, United Kingdom
3 Doctoral Training Centre for Integrative Systems Biology, The University of Manchester, Manchester, United Kingdom
4 School of Life Sciences, University of Warwick, Coventry, United Kingdom
5 School of Chemistry, The University of Manchester, Manchester, United Kingdom
6 School of Computer Science and Manchester Institute of Biotechnology, The University of Manchester, Manchester, United Kingdom
7 Center for Quantitative Medicine and Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut, USA
8 School of Computer Science, The University of Manchester, Manchester, United Kingdom
DOI
10.7287/peerj.preprints.146v4
Published
Accepted
Subject Areas
Biochemistry, Computational Biology, Mathematical Biology
Keywords
metabolism, modelling, simulation, systems biology, Saccharomyces cerevisiae, enzyme kinetics, pentose phosphate pathway, glycolysis, oxidative stress
Copyright
© 2014 Messiha et al.
Licence
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cite this article
Messiha HL, Kent E, Malys N, Carroll KM, Swainston N, Mendes P, Smallbone K. 2014. Enzyme characterisation and kinetic modelling of the pentose phosphate pathway in yeast. PeerJ PrePrints 2:e146v4

Abstract

We present the quantification and kinetic characterisation of the enzymes of the pentose phosphate pathway in Saccharomyces cerevisiae. The data are combined into a mathematical model that describes the dynamics of this system and allows us to predict changes in metabolite concentrations and fluxes in response to perturbations. We use the model to study the response of yeast to a glucose pulse. We then combine the model with an existing glycolysis model to study the effect of oxidative stress on carbohydrate metabolism. The combination of these two models was made possible by the standardised enzyme kinetic experiments carried out in both studies. This work demonstrates the feasibility of constructing larger network-scale models by merging smaller pathway-scale models.

Author Comment

Response to two reviewers. Added plots with data from enzyme kinetic experiments. Added one author, who was involved in data processing.

Additional Information

Competing Interests

The authors declare that they have no competing interests.

Author Contributions

Hanan L. Messiha conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Edward Kent performed the experiments, analyzed the data, wrote the paper.

Naglis Malys conceived and designed the experiments, performed the experiments, contributed reagents/materials/analysis tools, wrote the paper.

Kathleen M. Carroll performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper.

Neil Swainston analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.

Pedro Mendes conceived and designed the experiments, wrote the paper, reviewed drafts of the paper.

Kieran Smallbone conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.

Grant Disclosures

The following grant information was disclosed by the authors:

BBSRC and EPSRC grant BB/C008219, Pfizer and BBSRC grant BB/G529859,

EU FP7 grant 289434,

BBSRC grants BB/J019259 and BB/K019783,

NIH grant R01-GM080219

Data Deposition

The following information was supplied regarding the deposition of related data:

BioModels database, MODEL1311290000

BioModels database, MODEL1311290001

Funding

We thank the BBSRC and EPSRC for their financial support of this work (grant BB/C008219/1) through the Manchester Centre for Integrative Systems Biology. EK was funded by Pfizer Inc. and BBSRC (grant BB/G529859). KS and PM are grateful for the financial support of the EU FP7 project BioPreDyn (grant 289434). PM was also funded by BBSRC (grants BB/J019259 and BB/K019783) and NIH (R01-GM080219). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Enzyme characterisation and kinetic modelling of the pentose phosphate pathway in yeast
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