Connecting extracellular metabolomic measurements to intracellular flux states in yeast.

TitleConnecting extracellular metabolomic measurements to intracellular flux states in yeast.
Publication TypeJournal Article
Year of Publication2009
AuthorsMo ML, Palsson BØ, Herrgard MJ
JournalBMC systems biology
Volume3
Pagination37
PubMed Date2009
ISSN1752-0509
KeywordsAmino Acids, Extracellular Space, Gene Deletion, Genes, Fungal, Glutamate Dehydrogenase, Intracellular Space, Metabolic Networks and Pathways, Metabolomics, Models, Biological, Potassium, Quaternary Ammonium Compounds, Reproducibility of Results, Saccharomyces cerevisiae, Systems Biology
Abstract

BACKGROUND: Metabolomics has emerged as a powerful tool in the quantitative identification of physiological and disease-induced biological states. Extracellular metabolome or metabolic profiling data, in particular, can provide an insightful view of intracellular physiological states in a noninvasive manner.

RESULTS: We used an updated genome-scale metabolic network model of Saccharomyces cerevisiae, iMM904, to investigate how changes in the extracellular metabolome can be used to study systemic changes in intracellular metabolic states. The iMM904 metabolic network was reconstructed based on an existing genome-scale network, iND750, and includes 904 genes and 1,412 reactions. The network model was first validated by comparing 2,888 in silico single-gene deletion strain growth phenotype predictions to published experimental data. Extracellular metabolome data measured in response to environmental and genetic perturbations of ammonium assimilation pathways was then integrated with the iMM904 network in the form of relative overflow secretion constraints and a flux sampling approach was used to characterize candidate flux distributions allowed by these constraints. Predicted intracellular flux changes were consistent with published measurements on intracellular metabolite levels and fluxes. Patterns of predicted intracellular flux changes could also be used to correctly identify the regions of the metabolic network that were perturbed.

CONCLUSION: Our results indicate that integrating quantitative extracellular metabolomic profiles in a constraint-based framework enables inferring changes in intracellular metabolic flux states. Similar methods could potentially be applied towards analyzing biofluid metabolome variations related to human physiological and disease states.

Alternate JournalBMC Syst Biol
PubMed ID19321003

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