title: Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.|Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey, USA.
authors.forename: Junyoung O
authors.identifier: 0000-0001-9869-8993
authors.initials: JO
authors.lastname: Park
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Rubin
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.|Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Amador-Noguez
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.|Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Computer Science, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Shlomi
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.|Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
mesh_terms: D000818:Animals; D002460:Cell Line; D004798:Enzymes / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D004798:Enzymes