ArticleThe EMBO journal2002
Activation of system L heterodimeric amino acid exchangers by intracellular substrates.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 309 citations in OpenAlex.
- Resistance training partially restores age-related differences in skeletal muscle amino acid transporters - secondary analysis from two randomized controlled trials.The journal of nutrition, health & aging · 2026Trial
- Blocking mitochondrial leucine transamination enhances T-cell activation and improves T-cell immunity against OVA-producing EL4 lymphoma.British journal of cancer · 2026Article
- Aryl Sulfamoyl [Journal of medicinal chemistry · 2026Article
- The role of L-type amino acid transporter 1 in the pathogenicity ofMicrobiology spectrum · 2026Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Review
- Sustained reductions in valine and isoleucine mediate anti-cancer pharmacological effects of inhibiting amino acid transporter LAT1 in cancer cells.Cancer & metabolism · 2025Article
- The Saccharomyces cerevisiae amino acid transporter Lyp1 has a broad substrate spectrum.FEBS letters · 2025Article
- Structural basis of anticancer drug recognition and amino acid transport by LAT1.Nature communications · 2025Article
- The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.PNAS nexus · 2025Article
- Identification of Non-excitatory Amino Acids and Transporters Mediating the Irreversible Synaptic Silencing After Hypoxia.Translational stroke research · 2024Article
- High-level L-Gln compromises intestinal amino acid utilization efficiency and inhibits protein synthesis by GCN2/eIF2α/ATF4 signaling pathway in piglets fed low-crude protein diets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Trophoblast-specific overexpression of the LAT1 increases transplacental transport of essential amino acids and fetal growth in mice.PNAS nexus · 2024Article
- Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.Nature communications · 2024Article
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Overexpression of the LAT1 in primary human trophoblast cells increases the uptake of essential amino acids and activates mTOR signaling.Clinical science (London, England : 1979) · 2023Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging.Antioxidants (Basel, Switzerland) · 2023Review
- The Dysregulated MAD in Mad: A Neuro-theranostic Approach Through the Induction of Autophagic Biomarkers LC3B-II and ATG.Molecular neurobiology · 2023Review
- Novel Iron Chelator SK4 Drives Cytotoxicity through Inhibiting Mitochondrial Metabolism in Ovarian and Triple Negative Breast Cancer Cell Lines.Biomedicines · 2023Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
System L-type transport of large neutral amino acids is mediated by ubiquitous LAT1-4F2hc and epithelial LAT2-4F2hc. These heterodimers are thought to function as obligatory exchangers, but only influx properties have been studied in some detail up until now. Here we measured their intracellular substrate selectivity, affinity and exchange stoichiometry using the Xenopus oocyte expression system. Quantification of amino acid influx and efflux by HPLC demonstrated an obligatory amino acid exchange with 1:1 stoichiometry. Strong, differential trans-stimulations of amino acid influx by injected amino acids showed that the intracellular substrate availability limits the transport rate and that the efflux selectivity range resembles that of influx. Compared with high extracellular apparent affinities, LAT1- and LAT2-4F2hc displayed much lower intracellular apparent affinities (apparent K(m) in the millimolar range). Thus, the two system L amino acid transporters that are implicated in cell growth (LAT1-4F2hc) and transcellular transport (LAT2-4F2hc) are obligatory exchangers with relatively symmetrical substrate selectivities but strongly asymmetrical substrate affinities such that the intracellular amino acid concentration controls their activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.