Quantitative modelling of amino acid transport and homeostasis in mammalian cells.
A549 Cells
Amino Acid Transport Systems
/ chemistry
Amino Acids
/ metabolism
Animals
Biological Transport
Cell Line, Tumor
Cell Membrane
/ metabolism
Computer Simulation
Gene Expression
Homeostasis
/ genetics
Humans
Kinetics
Metabolomics
/ methods
Models, Statistical
Neuroglia
/ cytology
Oocytes
/ cytology
Xenopus laevis
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 09 2021
06 09 2021
Historique:
received:
08
12
2020
accepted:
13
08
2021
entrez:
7
9
2021
pubmed:
8
9
2021
medline:
6
10
2021
Statut:
epublish
Résumé
Homeostasis is one of the fundamental concepts in physiology. Despite remarkable progress in our molecular understanding of amino acid transport, metabolism and signaling, it remains unclear by what mechanisms cytosolic amino acid concentrations are maintained. We propose that amino acid transporters are the primary determinants of intracellular amino acid levels. We show that a cell's endowment with amino acid transporters can be deconvoluted experimentally and used this data to computationally simulate amino acid translocation across the plasma membrane. Transport simulation generates cytosolic amino acid concentrations that are close to those observed in vitro. Perturbations of the system are replicated in silico and can be applied to systems where only transcriptomic data are available. This work explains amino acid homeostasis at the systems-level, through a combination of secondary active transporters, functionally acting as loaders, harmonizers and controller transporters to generate a stable equilibrium of all amino acid concentrations.
Identifiants
pubmed: 34489418
doi: 10.1038/s41467-021-25563-x
pii: 10.1038/s41467-021-25563-x
pmc: PMC8421413
doi:
Substances chimiques
Amino Acid Transport Systems
0
Amino Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5282Informations de copyright
© 2021. The Author(s).
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