Regulation of Amino Acid Transport in Saccharomyces cerevisiae

Microbiology and Molecular Biology Reviews, Journal Year: 2019, Volume and Issue: 83(4)

Published: Oct. 15, 2019

We review the mechanisms responsible for amino acid homeostasis in Saccharomyces cerevisiae and other fungi. Amino is essential cell growth survival. Hence, de novo synthesis reactions, metabolic conversions, transport of acids are tightly regulated.

Language: Английский

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The Central Role of Amino Acids in Cancer Redox Homeostasis: Vulnerability Points of the Cancer Redox Code

Frontiers in Oncology, Journal Year: 2017, Volume and Issue: 7

Published: Dec. 21, 2017

A fine balance in reactive oxygen species (ROS) production and removal is of utmost importance for homeostasis all cells especially highly proliferating that encounter increased ROS due to enhanced metabolism. Consequently, these molecules requires coupling with antioxidant defense (AOD) within cells. This observed cancer allocate significant energy reserves maintain their intracellular redox balance. Glutathione (GSH), as a first line defense, represents the most important, non-enzymatic component together NADPH/NADP+ couple, which ensures maintenance pool reduced GSH. In this review, central role amino acids cancer, through GSH synthesis (cysteine, glutamate, glycine), NAD(P)H (serine, glutamine/glutamate) are illustrated. Special emphasis placed on acid transporters known be up-regulated cancers (such xCT ASCT2) homeostasis, thus indirectly, The varies (often described 'two-edged sword') during processes carcinogenesis, metastasis cancer-treatment. Therefore context-dependent specific initiation, progression dissemination well redox-dependent sensitivity/resistance neoplastic chemotherapy highlighted.

Language: Английский

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ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d -serine and neurodevelopment

Proceedings of the National Academy of Sciences, Journal Year: 2018, Volume and Issue: 115(38), P. 9628 - 9633

Published: Sept. 5, 2018

d -serine is a physiologic coagonist of NMDA receptors, but little known about the regulation its synthesis and synaptic turnover. The amino acid exchangers ASCT1 (Slc1a4) ASCT2 (Slc1a5) are candidates for regulating levels. Using KO mice, we report that ASCT1, rather than ASCT2, regulator metabolism. major uptake system in astrocytes can also export l via heteroexchange, supplying neurons with substrate synthesis. ASCT1-KO mice display lower levels brain along higher -alanine, -threonine, glycine. Deletion was associated neurodevelopmental alterations including hippocampal striatal volumes changes expression neurodevelopmental-relevant genes. Furthermore, exhibited deficits motor function, spatial learning, affective behavior, relative contributions vs. glycine mediating receptor activity. In vivo microdialysis demonstrated extracellular confirming altered These reminiscent some phenotypes by patients mutations. provide useful model potential therapeutic interventions aimed at correcting metabolic impairments

Language: Английский

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Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: July 19, 2018

The glutamine transporter ASCT2 (SLC1A5) is actively investigated as an oncological target, but the field lacks efficient inhibitors. A new group of inhibitors, 2-Amino-4-bis(aryloxybenzyl)aminobutanoic acids (AABA) were developed recently and shown to suppress tumor growth in preclinical vivo models. To test its specificity, we deleted two human cancer cell lines. Surprisingly, parental ASCT2-knockout cells was equally sensitive AABA compounds. compounds inhibited transport lacking ASCT2, not cells. Deletion amino acid depletion induced expression SNAT2 (SLC38A2), activity which by They also potently isoleucine uptake via LAT1 (SLC7A5), a that upregulated together with ASCT2. Inhibition confirmed recombinant Xenopus laevis oocytes. reported reduction pre-clinical models may be explained significant disruption homeostasis.

Language: Английский

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Quantitative modelling of amino acid transport and homeostasis in mammalian cells

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 6, 2021

Abstract Homeostasis is one of the fundamental concepts in physiology. Despite remarkable progress our molecular understanding amino acid transport, metabolism and signaling, it remains unclear by what mechanisms cytosolic concentrations are maintained. We propose that transporters primary determinants intracellular levels. show a cell’s endowment with can be deconvoluted experimentally used this data to computationally simulate translocation across plasma membrane. Transport simulation generates close those observed vitro. Perturbations system replicated silico applied systems where only transcriptomic available. This work explains homeostasis at systems-level, through combination secondary active transporters, functionally acting as loaders, harmonizers controller generate stable equilibrium all concentrations.

Language: Английский

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