ArticleNature chemical biology2016
Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
234 citing papers in PubMed.
- Apparent Saturation of Branched-Chain Amino Acid Catabolism After High Dietary Milk Protein Intake in Healthy Adults.The Journal of clinical endocrinology and metabolism · 2025Trial
- Global proteolysis during starvation governs proteome remodeling and a survival-regrowth trade-off in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Gibbs free energy landscape based on liver metabolome revealed thermodynamic robustness against fasting and obesity.iScience · 2026Article
- Trade-off between flux efficiency and metabolic control shapes enzyme allocation.Molecular systems biology · 2026Article
- Bacterial growth under confinement requires transcriptional adaptation to resist turgor pressure build-up.Nature communications · 2026Article
- Selective Redox Tuning Enables Potent Intracellular Reduction of Nicotinamide Cytosine Dinucleotide.Biomolecules · 2026Article
- Article
- Control theory analysis of dynamic metabolic response elucidates mitochondrial-cytoplasmic coupling and nutrient partitioning.bioRxiv : the preprint server for biology · 2026Article
- Discovery of 5' NAD capped viral RNAs reveals evolutionary divergent 5' metabolite capping across hepaciviruses.Nature communications · 2026Article
- Hemin Recapitulates the Labile Iron Pool in the Cellular Fenton Reaction with DNA.Chemical research in toxicology · 2026Article
- The total mass, copy number, and distribution of hormones in the human bloodstream.PLoS biology · 2026Article
- Machine Learning-Guided Synthetic Microbial Communities Enable Functional and Sustainable Degradation of Persistent Environmental Pollutants.Environmental science & technology · 2026Article
- Newcastle disease virus hijacks mitophagy to reprogram amino acid metabolism for enhanced replication.Autophagy · 2026Article
- Mimetics of in-cell and subcellular crowding and solvation for protein folding.Biochemical Society transactions · 2026Review
- Beyond Correlation: Constraint Architecture Explains Proteome-Metabolome Decoupling.International journal of molecular sciences · 2026Review
- Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Discovery of metabolites produced by reactions between central carbon metabolites and cysteine that mark inflammatory macrophages.bioRxiv : the preprint server for biology · 2026Article
- Malic enzyme-based system for transhydrogenation between nicotinamide cofactors.Synthetic and systems biotechnology · 2026Article
- Glutaredoxin 2 is essential for AML survival through mitochondrial permeability transition pore regulation.Blood · 2026Article
174 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.