Quantitative modelling of amino acid transport and homeostasis in mammalian cells
Gregory Gauthier-Coles,
Jade Vennitti,
Zhiduo Zhang,
William C. Comb,
Shuran Xing,
Kiran Javed,
Angelika Bröer and
Stefan Bröer ()
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Gregory Gauthier-Coles: Australian National University
Jade Vennitti: Australian National University
Zhiduo Zhang: Australian National University
William C. Comb: Axcella Health Inc.
Shuran Xing: Axcella Health Inc.
Kiran Javed: Australian National University
Angelika Bröer: Australian National University
Stefan Bröer: Australian National University
Nature Communications, 2021, vol. 12, issue 1, 1-18
Abstract:
Abstract 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.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25563-x
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DOI: 10.1038/s41467-021-25563-x
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