{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:00Z","timestamp":1792790400023,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["724003"],"award-info":[{"award-number":["724003"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM145744\u201001"],"award-info":[{"award-number":["GM145744\u201001"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP220046"],"award-info":[{"award-number":["RP220046"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP250402"],"award-info":[{"award-number":["RP250402"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I\u20102058\u201020210327"],"award-info":[{"award-number":["I\u20102058\u201020210327"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["CA142543"],"award-info":[{"award-number":["CA142543"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA245548"],"award-info":[{"award-number":["R01CA245548"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Tryptophan (Trp) is the largest and most structurally complex amino acid, yet it is the least abundant in the proteome. Its distinct indole ring and high carbon content allow it to give rise to several biologically active metabolites, including serotonin, kynurenine (Kyn), and indole\u20103\u2010pyruvate (I3P). Dysregulation of Trp metabolism has been implicated in a range of diseases, from depression to cancer. Investigating Trp and its metabolites in healthy tissues provides insight into how disease\u2010associated disruptions may be targeted selectively while preserving essential physiological functions. Whereas previous studies have typically focused on individual organs or single metabolic branches, our analysis spans 12 peripheral organs, the central nervous system, and serum in male and female (C57BL\/6) mice across three life stages: young (3\u2009weeks), adult (54\u2009weeks), and aged (74\u2009weeks). We identified striking tissue\u2010, sex\u2010, and age\u2010specific differences in Trp metabolism, including elevated levels of I3P and Kyn, both linked to tumor growth, in aging males. We also compared Trp metabolite profiles in tissues from mice fed a control defined diet versus a Trp\u2010deficient diet for three weeks. This intervention led to a marked reduction in circulating Trp and its metabolites, with more modest effects observed in the liver and central nervous system. These findings underscore the importance of organ\u2010specific and diet\u2010sensitive analyses of Trp metabolism for understanding its role in both normal physiology and disease. Establishing baseline levels of Trp metabolites across tissues may also provide a foundation for identifying organ\u2010specific metabolic reprogramming in cancer and other illnesses.<\/jats:p>","DOI":"10.1002\/2211-5463.70123","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:21:41Z","timestamp":1758280901000},"page":"52-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tryptophan metabolite atlas uncovers organ, age, and sex\u2010specific variations"],"prefix":"10.1002","volume":"16","author":[{"given":"Lizbeth","family":"Perez\u2010Castro","sequence":"first","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshan F.","family":"Nawas","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Kilgore","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A. S.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.Carmen","family":"Lafita\u2010Navarro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Lyda Hill Department of Bioinformatics University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-5087","authenticated-orcid":false,"given":"Maralice","family":"Conacci\u2010Sorrell","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Texas Southwestern Medical Center  Dallas USA"},{"name":"Hamon Center for Regenerative Science and Medicine University of Texas Southwestern Medical Center  Dallas USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center  Dallas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228776"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16245"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.004"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104827"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf9794"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17109"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12617"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.313007.118"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009117"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00196-X"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260028"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136974"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0740-x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.038"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178646917691938"},{"key":"e_1_2_11_17_1","first-page":"15","article-title":"Role of NAD(+), oxidative stress, and tryptophan metabolism in autism Spectrum disorders","volume":"6","author":"Essa MM","year":"2013","journal-title":"Int J Tryptophan Res"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8952520"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0420"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47868-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02565"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-821565-4.00008-0"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.04.009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.190139"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17799"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.01.010"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010181"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01375"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(86)90583-8"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.47.253.442"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c02381"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00313-x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44324-025-00067-0"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2639"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1872"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10491"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112945"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1966"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6467"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.02.001"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.01.051"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.43.100901.135828"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx7001965"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.327056.119"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm934"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.07.027"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.04.037"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.074765"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)91048-4"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.70123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T17:42:55Z","timestamp":1767634975000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.70123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/2211-5463.70123"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.70123","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]},"assertion":[{"value":"2025-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}