{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:17:55Z","timestamp":1791299875942,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["INST 90\/1048\u20101 FUGG"],"award-info":[{"award-number":["INST 90\/1048\u20101 FUGG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>Amino acids are important for cellular metabolism. Their uptake across the plasma membrane is mediated by transport proteins. Despite the fact that the organic anion transporting polypeptide 4C1 (OATP4C1, Uniprot: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/Q6ZQN7\">Q6ZQN7<\/jats:ext-link>) mediates transport of <jats:sc>l<\/jats:sc>\u2010arginine and <jats:sc>l<\/jats:sc>\u2010arginine derivatives, other members of the OATP family have not been characterized as amino acid transporters. The OATP family member OATP3A1 (gene symbol <jats:italic>SLCO3A1<\/jats:italic>, Uniprot: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.uniprot.org\/uniprot\/Q9UIG8\">Q9UIG8<\/jats:ext-link>) is ubiquitously expressed in human cells and highly expressed in many cancer tissues and cell lines. However, only a few substrates are known for OATP3A1. Accordingly, knowledge about its biological relevance is restricted. Our aim was to identify new substrates of OATP3A1 to gain insights into its (patho\u2010)physiological function. In an LC\u2010MS\u2010based untargeted metabolomics assay using untreated OATP3A1\u2010overexpressing HEK293 cells and control cells, we identified several amino acids as potential substrates of OATP3A1. Subsequent uptake experiments using exogenously added substrates revealed OATP3A1\u2010mediated transport of <jats:sc>l<\/jats:sc>\u2010tryptophan, <jats:sc>l<\/jats:sc>\u2010tyrosine, and <jats:sc>l<\/jats:sc>\u2010phenylalanine with 194.8\u2009\u00b1\u200928.7% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05), 226.2\u2009\u00b1\u200918.7% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and 235.2\u2009\u00b1\u200913.5% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), respectively, in OATP3A1\u2010overexpressing cells compared to control cells. Furthermore, kinetic transport parameters (<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub> values) were determined (Trp\u2009=\u200961.5\u2009\u00b1\u200914.2\u2009\u03bc<jats:sc>m<\/jats:sc>, Tyr\u2009= 220.8\u2009\u00b1\u200954.5\u2009\u03bc<jats:sc>m<\/jats:sc>, Phe\u2009=\u2009234.7\u2009\u00b1\u200920.6\u2009\u03bc<jats:sc>m<\/jats:sc>). In summary, we identified the amino acids <jats:sc>l<\/jats:sc>\u2010tryptophan, <jats:sc>l<\/jats:sc>\u2010tyrosine, and <jats:sc>l<\/jats:sc>\u2010phenylalanine as new substrates of OATP3A1. These findings could be used for a better understanding of (patho\u2010)physiological processes involving increased demand of amino acids, where OATP3A1 should be considered as an important uptake transporter of <jats:sc>l<\/jats:sc>\u2010tryptophan, <jats:sc>l<\/jats:sc>\u2010tyrosine, and <jats:sc>l<\/jats:sc>\u2010phenylalanine.<\/jats:p>","DOI":"10.1111\/febs.17255","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T09:54:59Z","timestamp":1724925299000},"page":"4732-4743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transport of aromatic amino acids <scp>l<\/scp>\u2010tryptophan, <scp>l<\/scp>\u2010tyrosine, and <scp>l<\/scp>\u2010phenylalanine by the organic anion transporting polypeptide (<scp>OATP<\/scp>) <scp>3A1<\/scp>"],"prefix":"10.1111","volume":"291","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4041-0249","authenticated-orcid":false,"given":"Daniela 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