Sterols and oxysterols in plasma from Smith-Lemli-Opitz syndrome patients
| Autor: | Jonas Abdel-Khalik, Michael Ogundare, Peter J. Crick, Brian W. Bigger, William J. Griffiths, Libin Xu, Ingemar Björkhem, Andrew A. M. Morris, Yuqin Wang, Mei Kwun Kwok, Ned A. Porter, Akira Honda, Cedric H.L. Shackleton, Peter E. Clayton, Karin Tuschl |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
medicine.medical_specialty 7-Dehydrocholesterol reductase Oxidoreductases Acting on CH-CH Group Donors congenital hereditary and neonatal diseases and abnormalities Oxysterol Free Radicals Endocrinology Diabetes and Metabolism Clinical Biochemistry Reductase Biochemistry Article 03 medical and health sciences 7-Dehydrocholesterol chemistry.chemical_compound Plasma Dehydrocholesterols Endocrinology Internal medicine Blood plasma medicine polycyclic compounds Humans Molecular Biology Liquid chromatography– Sterol mass spectrometry Cholesterol Cholestadienols nutritional and metabolic diseases Oxysterols Cell Biology medicine.disease 3. Good health Smith-Lemli-Opitz Syndrome Sterols 030104 developmental biology chemistry Smith–Lemli–Opitz syndrome Mutation 8-Dehydrocholesterol Molecular Medicine lipids (amino acids peptides and proteins) |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2016.03.018 |
| Popis: | Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-dehydrocholesterol reductase (Δ7-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 (0.5ng/mL). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|