Journal article 915 views 119 downloads
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders
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William Griffiths ,
Eylan Yutuc,
Jonas Abdel-Khalik,
Peter J. Crick,
Thomas Hearn,
Alison Dickson,
Brian W. Bigger,
Teresa Hoi-Yee Wu,
Anu Goenka,
Arunabha Ghosh,
Simon A. Jones,
Douglas F. Covey,
Daniel S. Ory,
Yuqin Wang
Free Radical Biology and Medicine
Swansea University Authors:
Eylan Yutuc , William Griffiths
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DOI (Published version): 10.1016/j.freeradbiomed.2019.04.020
Abstract
Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed...
| Published in: | Free Radical Biology and Medicine |
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| ISSN: | 08915849 |
| Published: |
Elsevier B.V.
2019
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa50061 |
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| Abstract: |
Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3β,5α,6β-triol, 7-OC and 7β-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3β,5α,6β-triol, 7-OC and 7β-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3β,5α,6β-trihydroxycholanoic, 3β-hydroxy-7-oxochol-5-enoic and 3β,7β-dihydroxychol-5-enoic acids, respectively. The intermediates in these pathways may be causative of some phenotypical features of, and/or have diagnostic value for, the lysosomal storage diseases, Niemann Pick types C and B and lysosomal acid lipase deficiency. Free radical derived oxysterols are metabolised in human to unusual bile acids via novel branches of the acidic pathway, intermediates in these pathways are observed in plasma. |
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