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Title: Metabolite concentrations, fluxes and free energies imply efficient enzyme usage

In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative Δ G throughout. For each reaction, Δ G is log proportional both to a concentration ratio (reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). In this paper, 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 Δ G for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with Δ G near zero. Across metabolism, we observe that absolute metabolite concentrations and Δ G are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant ( K m or K i). Finally, the observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.
Authors:
ORCiD logo [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Princeton Univ., Princeton, NJ (United States)
  2. Technion-Israel Institute of Technology, Haifa (Israel)
Publication Date:
Grant/Contract Number:
SC0012461
Type:
Accepted Manuscript
Journal Name:
Nature Chemical Biology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 7; Journal ID: ISSN 1552-4450
Publisher:
Nature Publishing Group
Research Org:
Princeton Univ., NJ (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biochemical reaction networks; mass spectrometry; metabolomics; systems biology
OSTI Identifier:
1347119