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Unravelling new pathways of sterol metabolism

Yuqin Wang, William Griffiths Orcid Logo

Current Opinion in Clinical Nutrition and Metabolic Care, Start page: 1

Swansea University Author: William Griffiths Orcid Logo

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DOI (Published version): 10.1097/MCO.0000000000000442

Abstract

Purpose of reviewTo update researchers of recently discovered metabolites of cholesterol and of its precursors and to suggest relevant metabolic pathways.Recent findingsPatients suffering from inborn errors of sterol biosynthesis, transport and metabolism display unusual metabolic pathways, which ma...

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Published in: Current Opinion in Clinical Nutrition and Metabolic Care
ISSN: 1363-1950
Published: 2017
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URI: https://cronfa.swan.ac.uk/Record/cronfa37645
first_indexed 2017-12-18T13:52:01Z
last_indexed 2018-02-09T05:31:15Z
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spelling 2018-01-19T16:00:13.7726352 v2 37645 2017-12-18 Unravelling new pathways of sterol metabolism 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 2017-12-18 MEDS Purpose of reviewTo update researchers of recently discovered metabolites of cholesterol and of its precursors and to suggest relevant metabolic pathways.Recent findingsPatients suffering from inborn errors of sterol biosynthesis, transport and metabolism display unusual metabolic pathways, which may be major routes in the diseased state but minor in the healthy individual. Although quantitatively minor, these pathways may still be important in healthy individuals. Four inborn errors of metabolism, Smith-Lemli-Opitz syndrome, cerebrotendinous xanthomatosis and Niemann Pick disease types B (NPB) and C (NPC) result from mutations in different genes but can generate elevated levels of the same sterol metabolite, 7-oxocholesterol, in plasma. How this molecule is metabolized further is of great interest as its metabolites may have an important role in embryonic development. A second metabolite, abundant in NPC and NPB diseases, cholestane-3β,5α,6β-triol (3β,5α,6β-triol), has recently been shown to be metabolized to the corresponding bile acid, 3β,5α,6β-trihydroxycholanoic acid, providing a diagnostic marker in plasma. The origin of cholestane-3β,5α,6β-triol is likely to be 3β-hydroxycholestan-5,6-epoxide, which can alternatively be metabolized to the tumour suppressor dendrogenin A (DDA). In breast tumours, DDA levels are found to be decreased compared with normal tissues linking sterol metabolism to cancer.SummaryUnusual sterol metabolites and pathways may not only provide markers of disease, but also clues towards cause and treatment. Journal Article Current Opinion in Clinical Nutrition and Metabolic Care 1 1363-1950 bile acid, cholesterol, oxysterol 31 12 2017 2017-12-31 10.1097/MCO.0000000000000442 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University RCUK, BB/N015932/1 2018-01-19T16:00:13.7726352 2017-12-18T10:02:17.3522065 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Yuqin Wang 1 William Griffiths 0000-0002-4129-6616 2 0037645-18122017100415.pdf WangCurrentOpinion2017.pdf 2017-12-18T10:04:15.2170000 Output 496905 application/pdf Version of Record true 2017-12-18T00:00:00.0000000 Released under a Creative Commons Attribution License 4.0 (CC-BY). true eng
title Unravelling new pathways of sterol metabolism
spellingShingle Unravelling new pathways of sterol metabolism
William Griffiths
title_short Unravelling new pathways of sterol metabolism
title_full Unravelling new pathways of sterol metabolism
title_fullStr Unravelling new pathways of sterol metabolism
title_full_unstemmed Unravelling new pathways of sterol metabolism
title_sort Unravelling new pathways of sterol metabolism
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_William Griffiths
author William Griffiths
author2 Yuqin Wang
William Griffiths
format Journal article
container_title Current Opinion in Clinical Nutrition and Metabolic Care
container_start_page 1
publishDate 2017
institution Swansea University
issn 1363-1950
doi_str_mv 10.1097/MCO.0000000000000442
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
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description Purpose of reviewTo update researchers of recently discovered metabolites of cholesterol and of its precursors and to suggest relevant metabolic pathways.Recent findingsPatients suffering from inborn errors of sterol biosynthesis, transport and metabolism display unusual metabolic pathways, which may be major routes in the diseased state but minor in the healthy individual. Although quantitatively minor, these pathways may still be important in healthy individuals. Four inborn errors of metabolism, Smith-Lemli-Opitz syndrome, cerebrotendinous xanthomatosis and Niemann Pick disease types B (NPB) and C (NPC) result from mutations in different genes but can generate elevated levels of the same sterol metabolite, 7-oxocholesterol, in plasma. How this molecule is metabolized further is of great interest as its metabolites may have an important role in embryonic development. A second metabolite, abundant in NPC and NPB diseases, cholestane-3β,5α,6β-triol (3β,5α,6β-triol), has recently been shown to be metabolized to the corresponding bile acid, 3β,5α,6β-trihydroxycholanoic acid, providing a diagnostic marker in plasma. The origin of cholestane-3β,5α,6β-triol is likely to be 3β-hydroxycholestan-5,6-epoxide, which can alternatively be metabolized to the tumour suppressor dendrogenin A (DDA). In breast tumours, DDA levels are found to be decreased compared with normal tissues linking sterol metabolism to cancer.SummaryUnusual sterol metabolites and pathways may not only provide markers of disease, but also clues towards cause and treatment.
published_date 2017-12-31T07:20:14Z
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