Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in Xenopus oocytes
Abstract
The System L transporter facilitates cellular import of large neutral amino acids (AAs) such as Leu, a potent activator of the intracellular target of rapamycin (TOR) pathway, which signals for cell growth. System L is an AA exchanger, proposed to accumulate certain AAs by coupling to dissipation of concentration gradient(s) of exchange substrates generated by secondary active AA transporters such as System A (SNAT2). We addressed the hypothesis that this type of coupling (termed tertiary active transport) acts as an indirect mechanism to extend the range of AA stimulating TOR to those transported by both Systems A and L (e.g., Gln) through downstream enhancement of Leu accumulation. System A overexpression enabled Xenopus oocytes to accumulate substrate AAs (notably Ser, Gln, Ala, Pro, Met; totaling 2.6 nmol/oocyte) from medium containing a physiological AA mixture at plasma concentrations. Net accumulation of System L (4F2hc-xLAT1) substrates from this medium by System L-overexpressing oocytes was increased by 90% (from 0.7 to 1.35 nmol/oocyte; mainly Leu, Ile) when Systems A and L were coexpressed, coincident with a decline in accumulation of specific System A substrates (Gln, Ser, Met), as expected if the latter were also System L substrates and functional coupling of the transport Systems occurred. AA flux coupling was confirmed as trans-stimulation of Leu influx in System L-expressing oocytes by Gln injection (0.5 nmol/oocyte). The observed changes in Leu accumulation are sufficient to activate the TOR pathway in oocytes, although intracellular AA metabolism limits the potential for AA accumulation by tertiary active transport in this system.
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The increase in glutamine can help drive leucine uptake because LAT1 transports glutamine out of the muscle as it transports leucine into the muscle in tertiary active transport.
“Interestingly, the increase in glutamine can help drive leucine uptake since LAT1 transports glutamine out of the muscle as it transports leucine into the muscle in a process called tertiary active transport [18].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [18]
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“Interestingly, the increase in glutamine can help drive leucine uptake since LAT1 transports glutamine out of the muscle as it transports leucine into the muscle in a process called tertiary active transport [18].”
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- Authors
- Baird, F. E., Bett, K. J., MacLean, C., Tee, A. R., Hundal, H. S., & Taylor, P. M.
- Affiliations
- University of Dundee (GB)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-09
- Volume
- 297
- Issue
- 3
- Pages
- E822-E829
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2116133379
- Cited by
- 83
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 12 · 2014: 7 · 2013: 6 · 2012: 8
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Funders
- Research Councils UK
- National Institutes of Health
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (C19477)
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant nutrient uptake and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- system L, system A, SNAT2, LAT1, amino acid transport, amino acid substitutions, TOR signaling, glutamine, Xenopus oocytes, amino acid metabolism
- MeSH terms
- Amino Acids, Animals, Biological Transport, Female, Models, Biological, Oocytes, Time Factors, Transfection, Xenopus, beta-Alanine, Gene Expression, Amino Acid Transport System A, Amino Acid Transport System L
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