{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:02:32Z","timestamp":1789243352979,"version":"build-2803163510"},"reference-count":95,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009508","name":"Skaggs School of Pharmacy and Pharmaceutical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009508","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>\n                    Cystathionine \u03b2\u2010synthase\u2010deficient homocystinuria (HCU) is a poorly understood, life\u2010threatening inborn error of sulfur metabolism. Analysis of hepatic glutathione (GSH) metabolism in a mouse model of HCU demonstrated significant depletion of cysteine, GSH, and GSH disulfide independent of the block in trans\u2010 sulfuration compared with wild\u2010type controls. HCU induced the expression of the catalytic and regulatory subunits of \u03b3\u2010glutamyl ligase, GSH synthase (GS), \u03b3\u2010glutamyl transpeptidase 1, 5\u2010oxoprolinase (OPLAH), and the GSH\u2010 dependent methylglyoxal detoxification enzyme, glyoxalase\u20101. Multiple components of the transcription factor nuclear factor (erythroid\u2010derived 2)\u2010like 2 (Nrf2)\u2010mediated antioxidant\u2010response regulatory axis were induced without any detectable activation of Nrf2. Metabolomic analysis revealed the accumulation of multiple \u03b3\u2010glutamyl amino acids and that plasma ophthalmate levels could serve as a noninvasive marker for hepatic redox stress. Neither cysteine, nor betaine treatment was able to reverse the observed enzyme inductions. Taurine treatment normalized the expression levels of \u03b3\u2010glutamyl ligase C\/M, GS, OPLAH, and glyoxalase\u20101, and reversed HCU\u2010 induced deficits in protein glutathionylation by acting to double GSH levels relative to controls. Collectively, our data indicate that the perturbation of the \u03b3\u2010glutamyl cycle could contribute to multiple sequelae in HCU and that taurine has significant therapeutic potential for both HCU and other diseases for which GSH depletion is a critical pathogenic factor.\u2014Maclean, K. N., Jiang, H., Aivazidis, S., Kim, E., Shearn, C. T., Harris, P. S., Petersen, D. R., Allen, R. H., Stabler, S. P., Roede, J. R. Taurine treatment prevents derangement of the hepatic \u03b3\u2010glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism. FASEB J. 32, 1265\u20101280 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700586r","type":"journal-article","created":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T10:05:54Z","timestamp":1509703554000},"page":"1265-1280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Taurine treatment prevents derangement of the hepatic \u03b3\u2010glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism"],"prefix":"10.1096","volume":"32","author":[{"given":"Kenneth N.","family":"Maclean","sequence":"first","affiliation":[{"name":"Department of Pediatrics Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos","family":"Aivazidis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin T.","family":"Shearn","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Health Sciences Center Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally P.","family":"Stabler","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Health Sciences Center Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Roede","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1","article-title":"The natural history of homocystinuria due to cystathionine \u03b2\u2010synthase deficiency","volume":"37","author":"Mudd S. H.","year":"1985","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77815-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(95)52007-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0311343"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.67.3.1248"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"7095","DOI":"10.1016\/S0021-9258(19)45858-4","article-title":"Partial reactions catalyzed by \u2010glutamylcysteine synthetase and evidence for an activated glutamate intermediate","volume":"246","author":"Orlowski M.","year":"1971","journal-title":"J. Biol. Chem."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.3.759"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(74)90206-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0021-9258(18)66212-X","article-title":"Synthesis of glutathione from gamma\u2010glutamylcysteine","volume":"201","author":"Snoke J. E.","year":"1953","journal-title":"J. Biol. Chem."},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.05.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10089"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.06.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.06.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.355172"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-253633"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.11.190"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.012"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.04.025"},{"key":"e_1_2_8_21_1","first-page":"283","volume-title":"Animal Nutrition","author":"Maynard L. A.","year":"1962"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.12.3404.3404"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601876200"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(98)00089-8"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.9715"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059653"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)02189-2"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(86)90590-7"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77041-1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(95)03928-P"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.01.018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80764-9"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)36569-X"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401947"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.46.120604.141046"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.47.33627"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1109"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050439"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.11.005"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3260167"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.25.15146"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050795"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115890"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1998.275.2.E359"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2007.04.004"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.149724"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-9006-9"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx200342b"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1515\/DMDI.2008.23.1-2.125"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.1865"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02576774"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a130387"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7923"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.11.5606"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi001088w"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-240770"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.013433"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470123195.ch7"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00176-8"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(96)00219-5"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(99)01094-0"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(96)01027-7"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00410-4"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3200321"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008382912096"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2010.10.013"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2015.1100730"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32082-3"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.11.018"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.263.6.C1181"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270123"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.08.006"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04644.x"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)56017-8"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0790475"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht402"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3088-5"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00550-0"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-015-9588-y"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.067"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015672625913"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.515155"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.10.014"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80374-8"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00442-X"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.07.021"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.4161\/cib.15654"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.077149"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.07.023"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4716"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules15031242"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)91909-0"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199208000-00008"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1996.88237.x"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.11.1444"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201700586R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201700586R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201700586R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:14:39Z","timestamp":1761693279000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201700586R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,3]]},"references-count":95,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1096\/fj.201700586R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201700586r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,3]]},"assertion":[{"value":"2007-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}