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

TitleMetabolite concentrations, fluxes and free energies imply efficient enzyme usage.
Publication TypeJournal Article
Year of Publication2016
AuthorsPark, JO, Rubin, SA, Xu, Y-F, Amador-Noguez, D, Fan, J, Shlomi, T, Rabinowitz, JD
JournalNat Chem Biol
Volume12
Issue7
Pagination482-9
Date Published2016 Jul 01
ISSN1552-4469
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.

DOI10.1038/nchembio.2077
Alternate JournalNat. Chem. Biol.
PubMed ID27159581
PubMed Central IDPMC4912430
Grant ListR01 CA163591 / CA / NCI NIH HHS / United States