Article abstract
Nature Chemical Biology 5, 593 - 599 (2009)
Published online: 28 June 2009 | doi:10.1038/nchembio.186
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli
Bryson D Bennett1, Elizabeth H Kimball1, Melissa Gao1, Robin Osterhout2, Stephen J Van Dien2 & Joshua D Rabinowitz1
Abstract
Absolute metabolite concentrations are critical to a quantitative understanding of cellular metabolism, as concentrations impact both the free energies and rates of metabolic reactions. Here we use LC-MS/MS to quantify more than 100 metabolite concentrations in aerobic, exponentially growing Escherichia coli with glucose, glycerol or acetate as the carbon source. The total observed intracellular metabolite pool was approximately 300 mM. A small number of metabolites dominate the metabolome on a molar basis, with glutamate being the most abundant. Metabolite concentration exceeds Km for most substrate-enzyme pairs. An exception is lower glycolysis, where concentrations of intermediates are near the Km of their consuming enzymes and all reactions are near equilibrium. This may facilitate efficient flux reversibility given thermodynamic and osmotic constraints. The data and analyses presented here highlight the ability to identify organizing metabolic principles from systems-level absolute metabolite concentration data.
- Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
- Genomatica, Inc., San Diego, California, USA.
Correspondence to: Joshua D Rabinowitz1 e-mail: joshr@princeton.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
A metabolic network described in absolute termsNature Chemical Biology News and Views (01 Aug 2009)
RESEARCH
Site-specific DNA binding using a variation of the double stranded RNA binding motifNature Structural Biology Letter (01 Jul 1998)
Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapyNature Biotechnology Research (01 Oct 2008)
Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome dataMolecular Systems Biology Article (20 Jun 2006)
See all 18 matches for Research
