ArticleNature metabolism2022
Circulating metabolite homeostasis achieved through mass action.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 52 citations in OpenAlex.
- Association of handgrip strength with the plasma metabolomic profile: secondary analysis of a protein intervention study.Metabolomics : Official journal of the Metabolomic Society · 2026Trial
- Loss of TCA cycle turning promotes stem cell function.bioRxiv : the preprint server for biology · 2026Article
- HIF-1α drives distinct aspects of hypoxia-induced glucose metabolism in intestinal epithelial cells.The Journal of biological chemistry · 2026Article
- A metabolic basis for motor deficits in mice lacking BCKDK.The Journal of nutritional biochemistry · 2026Article
- Glucose is dynamically regulated by time of day in humans and Drosophila.PLoS biology · 2026Article
- Circadian clock gates diurnal glucose utilization.PLoS biology · 2026Article
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- Predicting metabolic preferences through transcriptomics: a data-driven approach to align metabolic signatures with gene expression profiles.Biochemistry and biophysics reports · 2025Article
- Overflow metabolism in bacterial, yeast, and mammalian cells: different names, same game.Molecular systems biology · 2025Review
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- The regulatory role of exercise in heart failure and myocardial energy metabolism: A review.Biomolecules & biomedicine · 2025Review
- Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.Molecular metabolism · 2025Article
- Unraveling the Relation of Parkinson's Disease and Metabolites: A Combined Analysis of Stool and Plasma Metabolites Based on Untargeted Metabolomics Technology.CNS neuroscience & therapeutics · 2025Article
- Lactate homeostasis is maintained through regulation of glycolysis and lipolysis.Cell metabolism · 2025Article
- Annotation of Metabolites in Stable Isotope Tracing Untargeted Metabolomics via Khipu-web.Journal of the American Society for Mass Spectrometry · 2024Article
- Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes.Cells · 2024Review
- Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer.Cancer research · 2024Article
- Glucose Challenge Uncovers Temporal Fungibility of Metabolic Homeostasis over a day:night cycle.bioRxiv : the preprint server for biology · 2024Article
- Metabolic adaptation pilots the differentiation of human hematopoietic cells.Life science alliance · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Homeostasis maintains serum metabolites within physiological ranges. For glucose, this requires insulin, which suppresses glucose production while accelerating its consumption. For other circulating metabolites, a comparable master regulator has yet to be discovered. Here we show that, in mice, many circulating metabolites are cleared via the tricarboxylic acid cycle (TCA) cycle in linear proportionality to their circulating concentration. Abundant circulating metabolites (essential amino acids, serine, alanine, citrate, 3-hydroxybutyrate) were administered intravenously in perturbative amounts and their fluxes were measured using isotope labelling. The increased circulating concentrations induced by the perturbative infusions hardly altered production fluxes while linearly enhancing consumption fluxes and TCA contributions. The same mass action relationship between concentration and consumption flux largely held across feeding, fasting and high- and low-protein diets, with amino acid homeostasis during fasting further supported by enhanced endogenous protein catabolism. Thus, despite the copious regulatory machinery in mammals, circulating metabolite homeostasis is achieved substantially through mass action-driven oxidation.
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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.