{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:44:44Z","timestamp":1792122284722,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EB022015"],"award-info":[{"award-number":["EB022015"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Current theories regarding tryptophan's homeostatic regulation, which are derived from in vitro, post\u2010mortem, and cell\u2010culture studies, lack any direct evidence supporting their occurrence in living subjects. In response, here we have used 20\u00a0s resolution, multi\u2010hour plasma measurements to confirm, for the first time, that the cooperativity and tryptophan\u2010induced stabilization of tryptophan 2,3\u2010dioxygenase (TDO) seen in vitro and in cell culture hold in live, intact animals. For example, a model coupling these regulatory mechanisms with a constant tryptophan production rate from tissue reservoirs describes our in vivo measurements quantitatively, and provides high\u2010precision estimates of tryptophan flux and tryptophan\u2010induced TDO up\u2010regulation in individual subjects. In bridging a longstanding gap between ex vivo, post\u2010mortem, and cell culture investigations and the physiology of live, intact animals, an advance that had previously only been reported for glucose, our results highlight the transformative power of applying only\u2010recently\u2010available, seconds\u2010resolved metabolite measurements to the study of metabolic regulation.<\/jats:p>","DOI":"10.1002\/advs.77595","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:02:51Z","timestamp":1792119771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Highly\u2010Time\u2010Resolved Measurements of Tryptophan's Distribution and Homeostatic Regulation in Live, Intact Animals"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4263-725X","authenticated-orcid":false,"given":"Yuyang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea N.","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute of Collaborative Biotechnology University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1824-2007","authenticated-orcid":false,"given":"Zeki","family":"Duman","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3185-281X","authenticated-orcid":false,"given":"Rose Mery","family":"Bakestani","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-1534","authenticated-orcid":false,"given":"Carl M.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-4718","authenticated-orcid":false,"given":"Joao","family":"Hespanha","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3216-8863","authenticated-orcid":false,"given":"Tod","family":"Kippin","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences University of California Santa Barbara  Santa Barbara California USA"},{"name":"Neuroscience Research Institute University of California Santa Barbara  Santa Barbara California USA"},{"name":"Biological Engineering Graduate Program University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-8771","authenticated-orcid":false,"given":"Kevin W.","family":"Plaxco","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California Santa Barbara  Santa Barbara California USA"},{"name":"Biological Engineering Graduate Program University of California Santa Barbara  Santa Barbara California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"StatPearls","author":"Nakrani M. 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