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Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders
Eylan Yutuc 
,
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
,
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 |
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Elsevier B.V.
2019
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa50061 |
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| spelling |
2020-06-16T15:31:53.4558424 v2 50061 2019-04-23 Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2019-04-23 BMS 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. Journal Article Free Radical Biology and Medicine Elsevier B.V. 08915849 31 12 2019 2019-12-31 10.1016/j.freeradbiomed.2019.04.020 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University UKRI, BB/N015932/1, BB/I001735/1 2020-06-16T15:31:53.4558424 2019-04-23T13:34:50.7462462 Eylan Yutuc 0000-0001-9971-1950 1 William Griffiths 0000-0002-4129-6616 2 Eylan Yutuc 3 Jonas Abdel-Khalik 4 Peter J. Crick 5 Thomas Hearn 6 Alison Dickson 7 Brian W. Bigger 8 Teresa Hoi-Yee Wu 9 Anu Goenka 10 Arunabha Ghosh 11 Simon A. Jones 12 Douglas F. Covey 13 Daniel S. Ory 14 Yuqin Wang 15 0050061-28052019113432.pdf 50061.pdf 2019-05-28T11:34:32.9500000 Output 2303054 application/pdf Version of Record true 2019-05-28T00:00:00.0000000 This is an open access article distributed under a Creative Commons Attribution 4.0 (CC BY) license. true eng |
| title |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| spellingShingle |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders Eylan Yutuc William Griffiths |
| title_short |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| title_full |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| title_fullStr |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| title_full_unstemmed |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| title_sort |
Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders |
| author_id_str_mv |
99332f073ce913a9b7d8b6441b17516d 3316b1d1b524be1831790933eed1c26e |
| author_id_fullname_str_mv |
99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc 3316b1d1b524be1831790933eed1c26e_***_William Griffiths |
| author |
Eylan Yutuc William Griffiths |
| author2 |
Eylan Yutuc 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 |
| format |
Journal article |
| container_title |
Free Radical Biology and Medicine |
| publishDate |
2019 |
| institution |
Swansea University |
| issn |
08915849 |
| doi_str_mv |
10.1016/j.freeradbiomed.2019.04.020 |
| publisher |
Elsevier B.V. |
| document_store_str |
1 |
| active_str |
0 |
| description |
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. |
| published_date |
2019-12-31T04:01:21Z |
| _version_ |
1763753152194019328 |
| score |
11.013148 |