Email updates

Keep up to date with the latest news and content from BMC Systems Biology and BioMed Central.

Open Access Highly Accessed Research article

Connecting extracellular metabolomic measurements to intracellular flux states in yeast

Monica L Mo1, Bernhard Ø Palsson1 and Markus J Herrgård12*

Author Affiliations

1 Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA

2 Current address: Synthetic Genomics, Inc, 11149 N Torrey Pines Rd, La Jolla, CA 92037, USA

For all author emails, please log on.

BMC Systems Biology 2009, 3:37  doi:10.1186/1752-0509-3-37

Published: 25 March 2009

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.