Network thermodynamic curation of human and yeast genome-scale metabolic models

Martinez, Veronica S., Quek, Lake-Ee and Nielsen, Lars K. (2014) Network thermodynamic curation of human and yeast genome-scale metabolic models. Biophysical Journal, 107 2: 493-503. doi:10.1016/j.bpj.2014.05.029

Author Martinez, Veronica S.
Quek, Lake-Ee
Nielsen, Lars K.
Title Network thermodynamic curation of human and yeast genome-scale metabolic models
Journal name Biophysical Journal   Check publisher's open access policy
ISSN 1542-0086
Publication date 2014-07-15
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.bpj.2014.05.029
Open Access Status
Volume 107
Issue 2
Start page 493
End page 503
Total pages 11
Place of publication St Louis, MO United States
Publisher Cell Press
Collection year 2015
Language eng
Abstract Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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