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We reported recently that radiolabeled 7K delivered to rodents in a modified lipoprotein or chylomicron remnantlike emulsion, both cleared predominantly by the liver, was rapidly excreted into the intestine as water\u2010soluble products, presumably bile acids. Herein, we aimed to elucidate the early or initial reactions in 7K metabolism. The hypothesis was tested that sterol 27\u2010hydroxylase, a mitochondrial cytochrome P450 and the first enzyme of the acidic bile acid pathway, is responsible for the initial metabolism of 7K by HepG2 cells, a human hepatoblastoma cell\u2010line. The 27\u2010hydroxylated product of 7K (27OH\u20107K) was shown to be the initial, lipid\u2010soluble product of 7K metabolism. It was produced in mitochondrial incubations and whole cells and was readily released into the media from cells. Intact cells generated metabolites of 7K that had undergone conversion from lipid\u2010soluble precusors to water\u2010soluble products rapidly and extensively. Their production was ablated with cyclosporin A, a sterol 27\u2010hydroxylase inhibitor. Furthermore, we demonstrated the effectiveness of two novel selective inhibitors of this enzyme, GW273297X and GI268267X. These inhibitors also ablated the production of water\u2010soluble products by cells; and the inhibitor of choice, GW273297X, decreased the production of 27OH\u20107K in mitochondrial preparations. This is the first study to demonstrate that sterol 27\u2010hydroxylase plays an important role in the metabolism of oxysterols such as 7K in liver cells.<\/jats:p>","DOI":"10.1007\/s11745-001-0775-8","type":"journal-article","created":{"date-parts":[[2006,11,13]],"date-time":"2006-11-13T15:03:30Z","timestamp":1163430210000},"page":"701-711","source":"Crossref","is-referenced-by-count":50,"title":["Metabolism of an oxysterol, 7\u2010ketocholesterol, by sterol 27\u2010hydroxylase in hepG2 cells"],"prefix":"10.1002","volume":"36","author":[{"given":"Malcolm A.","family":"Lyons","sequence":"first","affiliation":[{"name":"Cell Biology Group Heart Research Institute Sydney New South Wales 2050 Australia"},{"name":"The Jackson Laboratory Box 213, 600 Main St. Bar Harbor ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Cell Biology Group Heart Research Institute Sydney New South Wales 2050 Australia"},{"name":"Department of Molecular Genetics University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas TX 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,7]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118436"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00196-8"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02522641"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(98)00123-X"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(91)90051-4"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(89)90136-6"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37619-7"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37148-0"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-6915(95)00094-1"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022029900033719"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535656"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf970431"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.1993.tb03064.x"},{"key":"e_1_2_2_15_1","first-page":"71","volume-title":"Biological Effects of Cholesterol Oxides","author":"Addis P.B.","year":"1992"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsfa.2740550402"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000012737"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2621.1991.tb05396.x"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-997-0114-0"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02536627"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535405"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.3891\/acta.chem.scand.22-1595"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)63329-6"},{"key":"e_1_2_2_24_1","first-page":"153","article-title":"Metabolic Fate of Ingested and Injected 7\u2010Ketocholesterol in the Rabbit","volume":"2","author":"Sarma J.S.M.","year":"1976","journal-title":"Artery"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)34901-4"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(01)00083-X"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(81)90025-1"},{"key":"e_1_2_2_28_1","first-page":"103","article-title":"Formation and Metabolism of Chylomicrons","volume":"28","author":"Redgrave T.G.","year":"1983","journal-title":"Int. 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