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Nat Chem Biol. 2016 Jul;12(7):482-9. doi: 10.1038/nchembio.2077. Epub 2016 May 2.

Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.

Author information

1
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
2
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA.
3
Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
4
Department of Computer Science, Technion-Israel Institute of Technology, Haifa, Israel.

Abstract

In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative ΔG throughout. For each reaction, ΔG is log proportional both to a concentration ratio (reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). Here we use isotope labeling to measure absolute metabolite concentrations and fluxes in Escherichia coli, yeast and a mammalian cell line. We then integrate this information to obtain a unified set of concentrations and ΔG for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with ΔG near zero. Across metabolism, we observe that absolute metabolite concentrations and ΔG are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant (Km or Ki). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.

PMID:
27159581
PMCID:
PMC4912430
DOI:
10.1038/nchembio.2077
[Indexed for MEDLINE]
Free PMC Article

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