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This study compared metabolic kinetics between free Trp and protein-bound Trp from soy protein isolate (SPI) and sheep whey protein (SWP). A novel UPLC-TQ\/MS assay was built to quantify Trp and its metabolites simultaneously: 5-hydroxytryptophan (5-HTP), kynurenic acid (Kyna), indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA). Pharmacokinetic profiling showed free Trp peaked rapidly in rats. Tissue distribution exhibited distinct enrichment: Trp in heart and adipose, 5-HTP in kidney and epididymal fat, Kyna in kidney and brown fat, and IAA\/IPA in brain. Relative to free Trp, SPI and SWP delayed metabolite release and boosted microbial Trp conversion to IAA and IPA. SPI activated the 5-hydroxytryptamine pathway, raising plasma 5-HTP and fecal IAA; SWP favored the kynurenine pathway, elevating plasma Kyna and fecal IPA. These findings highlight differential outcomes of free versus protein-bound Trp supplementation.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05239","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:04:47Z","timestamp":1785949487000},"page":"25717-25732","source":"Crossref","is-referenced-by-count":0,"title":["Kinetic Profiling of Tryptophan and Its Metabolites\nfrom Sheep Whey and Soy Protein Isolate in Rats: Toward Personalized\nTryptophan Supplementation"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8535-1620","authenticated-orcid":true,"given":"Haoyan","family":"Zhu","sequence":"first","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]},{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2045-9611","authenticated-orcid":true,"given":"Xinwei","family":"Tian","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiheng","family":"Niu","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Han","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8039-0525","authenticated-orcid":true,"given":"Xingbin","family":"Yang","sequence":"additional","affiliation":[{"name":"Shaanxi Normal University , , ,","place":["Xi\u2019an, China, 710119"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"6","key":"2026081910171162100_cit1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan\nMetabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host\nMicrobe"},{"issue":"13","key":"2026081910171162100_cit2","doi-asserted-by":"publisher","first-page":"6787","DOI":"10.1021\/acs.jafc.3c06419","article-title":"Recent Advances in Current Uptake\nSituation, Metabolic and Nutritional Characteristics, Health, and\nSafety of Dietary Tryptophan","volume":"72","author":"Zhu","year":"2024","journal-title":"J. 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Agric.\nFood Chem."},{"issue":"21","key":"2026081910171162100_cit43","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022112963","article-title":"A Tryptophan\nMetabolite Made by a Gut Microbiome Eukaryote Induces Pro-Inflammatory\nT Cells","volume":"42","author":"Wojciech","year":"2023","journal-title":"EMBO J."}],"container-title":["Journal of Agricultural and Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c05239","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/32\/25717\/66418288\/acs.jafc.6c05239.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/32\/25717\/66418288\/acs.jafc.6c05239.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:41:01Z","timestamp":1787150461000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/32\/25717\/5246489\/Kinetic-Profiling-of-Tryptophan-and-Its"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":43,"journal-issue":{"issue":"32","published-online":{"date-parts":[[2026,8,5]]},"published-print":{"date-parts":[[2026,8,19]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c05239","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}