{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T01:05:46Z","timestamp":1776215146819,"version":"3.50.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Support for Pioneering Research Initiated"},{"name":"Next Generation","award":["JPMJSP2109"],"award-info":[{"award-number":["JPMJSP2109"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Grants-in-Aid for Scientific Research on Innovative Areas","award":["19H05772"],"award-info":[{"award-number":["19H05772"]}]},{"name":"Scientific Research","award":["21H04920"],"award-info":[{"award-number":["21H04920"]}]},{"name":"Scientific Research","award":["24H00749"],"award-info":[{"award-number":["24H00749"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\u03b3-Glutamyl-\u03b2-cyanoalanylglycine (gEcnAG) is a glutathione analog in which the cysteine moiety in glutathione is replaced with \u03b2-cyanoalanine, a known plant cyanide metabolite. Previously, gEcnAG was detected in the liver of rats and chicks exposed to \u03b2-cyanoalanine. We reported the detection of gEcnAG in na\u00efve mammalian cells using liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). LC-QTOF-MS analysis enabled high-resolution confirmation (exact mass determination and MS\/MS fragmentation) of the gEcnAG structure. The detection of gEcnAG in rat pheochromocytoma (PC12) cells that were not exposed to \u03b2-cyanoalanine suggests its endogenous production. Furthermore, the inhibition of myeloperoxidase, an enzyme potentially required for endogenous cyanide generation, decreased gEcnAG levels in PC12 cells. This supports the notion that PC12 cells intrinsically produce cyanide, unlike HepG2 cells, which exhibited lower intracellular gEcnAG levels. Notably, \u03b2-cyanoalanine was undetectable in PC12 cells. Moreover, depleting glutathione with buthionine sulfoximine reduced intracellular gEcnAG levels, whereas supplementation with glutathione reduced ethyl ester increased them. These observations suggest that endogenous gEcnAG may be generated from glutathione, potentially through its reaction with endogenous cyanide. Our findings implicate gEcnAG as a possible metabolite of endogenous cyanide.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae107","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T18:57:20Z","timestamp":1723921040000},"page":"19-24","source":"Crossref","is-referenced-by-count":1,"title":["Elucidation of \u03b3-glutamyl-\u03b2-cyanoalanylglycine biosynthesis in mammalian cells by LC-QTOF-MS"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1724-9293","authenticated-orcid":false,"given":"Ryu","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University , Chiba 260-8675,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-5186","authenticated-orcid":false,"given":"Yoshikazu","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, Chiba University , Chiba 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-1828","authenticated-orcid":false,"given":"Yasumitsu","family":"Ogra","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Chiba University , Chiba 260-8675,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"issue":"26","key":"2026041420131212800_kfae107-B1","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1007\/s00216-023-04939-6","article-title":"Concurrent determination of cyanide and thiocyanate in human and swine antemortem and postmortem blood by high-performance liquid chromatography\u2013tandem mass spectrometry","volume":"415","author":"Alluhayb","year":"2023","journal-title":"Anal Bioanal 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