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J Lipid Res. 2014 Jun;55(6):1165-72. doi: 10.1194/jlr.P048603. Epub 2014 Apr 25.

On the formation of 7-ketocholesterol from 7-dehydrocholesterol in patients with CTX and SLO.

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Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
Sachs' Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Östersund Hospital, Östersund, Sweden.
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN.
Department of Clinical Medicine, Faculty of Health Science, University of Tromsö and Division of Cardiothoracic and Respiratory Medicine, University Hospital North Norway, Tromsö, Norway.
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Institute of Mass Spectrometry, College of Medicine, Swansea University, Singleton Park, Swansea, UK.


A new mechanism for formation of 7-ketocholesterol was recently described involving cytochrome P-450 (CYP)7A1-catalyzed conversion of 7-dehydrocholesterol into 7-ketocholesterol with cholesterol-7,8-epoxide as a side product. Some patients with cerebrotendinous xanthomatosis (CTX) and all patients with Smith-Lemli-Opitz syndrome (SLO) have markedly increased levels of 7-dehydrocholesterol in plasma and tissues. In addition, the former patients have markedly upregulated CYP7A1. We hypothesized that these patients may produce 7-ketocholesterol from 7-dehydrocholesterol with formation of cholesterol-7,8-epoxide as a side product. In accord with this hypothesis, two patients with CTX were found to have increased levels of 7-ketocholesterol and 7-dehydrocholesterol, as well as a significant level of cholesterol-7,8-epoxide. The latter steroid was not detectable in plasma from healthy volunteers. Downregulation of CYP7A1 activity by treatment with chenodeoxycholic acid reduced the levels of 7-ketocholesterol in parallel with decreased levels of 7-dehydrocholesterol and cholesterol-7,8-epoxide. Three patients with SLO were found to have markedly elevated levels of 7-ketocholesterol as well as high levels of cholesterol-7,8-epoxide. The results support the hypothesis that 7-dehydrocholesterol is a precursor to 7-ketocholesterol in SLO and some patients with CTX.


Smith-Lemli-Opitz syndrome; cerebrotendinous xanthomatosis; cholesterol 7,8-epoxide; cytochrome P-450 7A1; liquid chromatography-mass spectrometryn

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