{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T19:58:39Z","timestamp":1760644719113},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,15]]},"abstract":"<jats:p>Several halogenated alkenes are metabolized in part to cysteine S-conjugates, which are mitochondrial toxicants of kidney and, to a lesser extent, other organs. Toxicity is due to cysteine S-conjugate \u03b2-lyases, which convert the cysteine S-conjugate into pyruvate, ammonia and a reactive sulphur-containing fragment. A section of the human population is exposed to halogenated alkenes. To understand the health effects of such exposure, it is important to identify cysteine S-conjugate \u03b2-lyases that contribute to mitochondrial damage. Mitochondrial aspartate aminotransferase [Cooper, Bruschi, Iriarte and Martinez-Carrion (2002) Biochem. J. 368, 253\u2013261] and mitochondrial branched-chain aminotransferase [Cooper, Bruschi, Conway and Hutson (2003) Biochem. Pharmacol. 65, 181\u2013192] exhibit \u03b2-lyase activity toward S-(1,2-dichlorovinyl)-l-cysteine (the cysteine S-conjugate of trichloroethylene) and S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (the cysteine S-conjugate of tetrafluoroethylene). Turnover leads to eventual inactivation of these enzymes. Here we report that mitochondrial l-alanine\u2013glyoxylate aminotransferase II, which, in the rat, is most active in kidney, catalyses cysteine S-conjugate \u03b2-lyase reactions with S-(1,1,2,2-tetrafluoroethyl)-l-cysteine, S-(1,2-dichlorovinyl)-l-cysteine and S-(benzothiazolyl-l-cysteine); turnover leads to inactivation. Previous workers showed that the reactive-sulphur-containing fragment released from S-(1,1,2,2-tetrafluoroethyl)-l-cysteine and S-(1,2-dichlorovinyl)-l-cysteine is toxic by acting as a thioacylating agent \u2013 particularly of lysine residues in nearby proteins. Toxicity, however, may also involve \u2018self-inactivation\u2019 of key enzymes. The present findings suggest that alanine\u2013glyoxylate aminotransferase II may be an important factor in the well-established targeting of rat kidney mitochondria by toxic halogenated cysteine S-conjugates. Previous reports suggest that alanine\u2013glyoxylate aminotransferase II is absent in some humans, but present in others. Alanine\u2013glyoxylate aminotransferase II may contribute to the bioactivation (toxification) of halogenated cysteine S-conjugates in a subset of individuals exposed to halogenated alkenes.<\/jats:p>","DOI":"10.1042\/bj20030988","type":"journal-article","created":{"date-parts":[[2003,11,11]],"date-time":"2003-11-11T15:45:26Z","timestamp":1068565526000},"page":"169-178","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["l-Alanine\u2013glyoxylate aminotransferase II of rat kidney and liver mitochondria possesses cysteine S-conjugate \u03b2-lyase activity: a contributing factor to the nephrotoxicity\/hepatotoxicity of halogenated alkenes?"],"prefix":"10.1042","volume":"376","author":[{"given":"Arthur J. L.","family":"COOPER","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Weill Medical College of Cornell University, 1600 York Avenue, New York, NY 10021, U.S.A."},{"name":"Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1600 York Avenue, New York, NY 10021, U.S.A."},{"name":"Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York, NY 10605, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris F.","family":"KRASNIKOV","sequence":"additional","affiliation":[{"name":"Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York, NY 10605, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etsuo","family":"OKUNO","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Wakayama Medical University, Wakayama 641-0012, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"JEITNER","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1600 York Avenue, New York, NY 10021, U.S.A."},{"name":"Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York, NY 10605, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/376\/1\/169\/712311\/bj3760169.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/376\/1\/169\/712311\/bj3760169.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T14:40:44Z","timestamp":1637592044000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/376\/1\/169\/43929\/l-Alanine-glyoxylate-aminotransferase-II-of-rat"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,11,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj20030988","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,15]]}}}