Circulating metabolite homeostasis achieved through mass action.

Autor: Li X; Department of Molecular Biology, Princeton University, Princeton, NJ, USA., Hui S; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.; Department of Molecular Metabolism, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Mirek ET; Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA., Jonsson WO; Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA., Anthony TG; Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA., Lee WD; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.; Department of Chemistry, Princeton University, Princeton, NJ, USA., Zeng X; Department of Chemistry, Princeton University, Princeton, NJ, USA., Jang C; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. choljang@uci.edu.; Department of Biological Chemistry, University of California Irvine, Irvine, CA, USA. choljang@uci.edu., Rabinowitz JD; Department of Molecular Biology, Princeton University, Princeton, NJ, USA. joshr@princeton.edu.; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA. joshr@princeton.edu.; Department of Chemistry, Princeton University, Princeton, NJ, USA. joshr@princeton.edu.; Ludwig Institute for Cancer Research, Princeton Branch, Princeton, NJ, USA. joshr@princeton.edu.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2022 Jan; Vol. 4 (1), pp. 141-152. Date of Electronic Publication: 2022 Jan 20.
DOI: 10.1038/s42255-021-00517-1
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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