Journal
NATURE CHEMICAL BIOLOGY
Volume 12, Issue 7, Pages 482-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2077
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Funding
- Howard Hughes Medical Institute international student research fellowship
- US Department of Energy [DE-SC0012461]
- US National Institutes of Health R01grant [1R01CA163591]
- DRC [2P30DK019525-37]
- U.S. Department of Energy (DOE) [DE-SC0012461] Funding Source: U.S. Department of Energy (DOE)
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In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative Delta G throughout. For each reaction, Delta G 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 Delta G for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with Delta G near zero. Across metabolism, we observe that absolute metabolite concentrations and Delta 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). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints.
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