Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients. Issue 169 (May 2017)

• Record Type: Journal Article
• Authors: Griffiths, William J.; Abdel-Khalik, Jonas; Crick, Peter J.; Ogundare, Michael; Shackleton, Cedric H.; Tuschl, Karin; Kwok, Mei Kwun; Bigger, Brian W.; Morris, Andrew A.; Honda, Akira; Xu, Libin; Porter, Ned A.; Björkhem, Ingemar; Clayton, Peter T.; Wang, Yuqin
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 169(2017)
• Page Start: 77
• Page End: 87
• Publication Date: 2017-05
• Subjects: Oxysterol -- Sterol -- 7-Dehydrocholesterol -- 8-Dehydrocholesterol -- 7-Dehydrocholesterol reductase -- Liquid chromatography– -- mass spectrometry; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2016.03.018
• Languages: English
• ISSNs: 0960-0760

Abstract

Graphical abstract: Highlights: 26-Hydroxy- and 24(or 25)-hydroxy-8-dehydrocholesterol identified in SLOS plasma. Enhanced concentrations of 7β-hydroxy- and 7-oxo-cholesterol in SLOS plasma. Free radical generated 3β, 5α-dihydroxycholest-7-en-6-one found in SLOS plasma Abstract: Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ 7 -sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-dehydrocholesterol, 3β, 5α-dihydroxycholest-7-en-6-one and 7α, 8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5 ng/mL).