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Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation

William Griffiths Orcid Logo, Ian Gilmore, Eylan Yutuc Orcid Logo, Jonas Abdel-Khalik, Peter J. Crick, Thomas Hearn, Alison Dickson, Brian W. Bigger, Teresa Hoi-Yee Wu, Anu Goenka, Arunabha Ghosh, Simon A. Jones, Yuqin Wang Orcid Logo

Journal of Lipid Research, Volume: 59, Issue: 6, Pages: 1058 - 1070

Swansea University Authors: William Griffiths Orcid Logo, Eylan Yutuc Orcid Logo, Yuqin Wang Orcid Logo

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DOI (Published version): 10.1194/jlr.d083246

Abstract

7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC) and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples, however, in disease their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosoma...

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Published in: Journal of Lipid Research
ISSN: 0022-2275 1539-7262
Published: American Society for Biochemistry & Molecular Biology (ASBMB) 2018
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URI: https://cronfa.swan.ac.uk/Record/cronfa39367
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This is the case in plasma from patients suffering from some lysosomal storage disorders e.g. Niemann Pick disease type C, or the inborn errors of sterol metabolism e.g. Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis. A complication in the analysis of 7-OC and 5,6-EC is that they can also be formed ex vivo from cholesterol during sample handling in air causing confusion with molecules formed in vivo. When formed endogenously 7-OC, 5,6-EC and 3&#x3B2;,5&#x3B1;,6&#x3B2;-triol can be converted to bile acids. Here, we describe methodology based on chemical derivatisation and liquid chromatography &#x2013; mass spectrometry with multistage fragmentation (MSn) to identify the necessary intermediates in the conversion of 7-OC to 3&#x3B2;-hydroxy-7-oxochol-5-enoic acid and 5,6-EC and 3&#x3B2;,5&#x3B1;,6&#x3B2;-triol to 3&#x3B2;,5&#x3B1;,6&#x3B2;-trihydroxycholanoic acid. Identification of intermediate metabolites is facilitated by their unusual MSn fragmentation patterns. 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spelling 2020-11-02T17:05:12.6902538 v2 39367 2018-04-11 Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation 3316b1d1b524be1831790933eed1c26e 0000-0002-4129-6616 William Griffiths William Griffiths true false 99332f073ce913a9b7d8b6441b17516d 0000-0001-9971-1950 Eylan Yutuc Eylan Yutuc true false c92729b58622f9fdf6a0e7d8f4ce5081 0000-0002-3063-3066 Yuqin Wang Yuqin Wang true false 2018-04-11 BMS 7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC) and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples, however, in disease their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosomal storage disorders e.g. Niemann Pick disease type C, or the inborn errors of sterol metabolism e.g. Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis. A complication in the analysis of 7-OC and 5,6-EC is that they can also be formed ex vivo from cholesterol during sample handling in air causing confusion with molecules formed in vivo. When formed endogenously 7-OC, 5,6-EC and 3β,5α,6β-triol can be converted to bile acids. Here, we describe methodology based on chemical derivatisation and liquid chromatography – mass spectrometry with multistage fragmentation (MSn) to identify the necessary intermediates in the conversion of 7-OC to 3β-hydroxy-7-oxochol-5-enoic acid and 5,6-EC and 3β,5α,6β-triol to 3β,5α,6β-trihydroxycholanoic acid. Identification of intermediate metabolites is facilitated by their unusual MSn fragmentation patterns. Semi-quantitative measurements are possible, but absolute values await the synthesis of isotope-labelled standards. Journal Article Journal of Lipid Research 59 6 1058 1070 American Society for Biochemistry & Molecular Biology (ASBMB) 0022-2275 1539-7262 1 6 2018 2018-06-01 10.1194/jlr.d083246 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University RCUK, BB/N015932/1 2020-11-02T17:05:12.6902538 2018-04-11T11:14:32.8600419 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine William Griffiths 0000-0002-4129-6616 1 Ian Gilmore 2 Eylan Yutuc 0000-0001-9971-1950 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 Yuqin Wang 0000-0002-3063-3066 13 0039367-26042018124245.pdf 39367.pdf 2018-04-26T12:42:45.5830000 Output 2065642 application/pdf Version of Record true Released under the terms of the Creative Commons CC-BY license. true eng http://creativecommons.org/licenses/by/4.0/
title Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
spellingShingle Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
William Griffiths
Eylan Yutuc
Yuqin Wang
title_short Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
title_full Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
title_fullStr Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
title_full_unstemmed Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
title_sort Identification of unusual oxysterols and bile acids with 7-oxo or 3β,5α,6β-trihydroxy functions in human plasma by charge-tagging mass spectrometry with multistage fragmentation
author_id_str_mv 3316b1d1b524be1831790933eed1c26e
99332f073ce913a9b7d8b6441b17516d
c92729b58622f9fdf6a0e7d8f4ce5081
author_id_fullname_str_mv 3316b1d1b524be1831790933eed1c26e_***_William Griffiths
99332f073ce913a9b7d8b6441b17516d_***_Eylan Yutuc
c92729b58622f9fdf6a0e7d8f4ce5081_***_Yuqin Wang
author William Griffiths
Eylan Yutuc
Yuqin Wang
author2 William Griffiths
Ian Gilmore
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
Yuqin Wang
format Journal article
container_title Journal of Lipid Research
container_volume 59
container_issue 6
container_start_page 1058
publishDate 2018
institution Swansea University
issn 0022-2275
1539-7262
doi_str_mv 10.1194/jlr.d083246
publisher American Society for Biochemistry & Molecular Biology (ASBMB)
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
active_str 0
description 7-Oxocholesterol (7-OC), 5,6-epoxycholesterol (5,6-EC) and its hydrolysis product cholestane-3β,5α,6β-triol (3β,5α,6β-triol) are normally minor oxysterols in human samples, however, in disease their levels may be greatly elevated. This is the case in plasma from patients suffering from some lysosomal storage disorders e.g. Niemann Pick disease type C, or the inborn errors of sterol metabolism e.g. Smith-Lemli-Opitz syndrome and cerebrotendinous xanthomatosis. A complication in the analysis of 7-OC and 5,6-EC is that they can also be formed ex vivo from cholesterol during sample handling in air causing confusion with molecules formed in vivo. When formed endogenously 7-OC, 5,6-EC and 3β,5α,6β-triol can be converted to bile acids. Here, we describe methodology based on chemical derivatisation and liquid chromatography – mass spectrometry with multistage fragmentation (MSn) to identify the necessary intermediates in the conversion of 7-OC to 3β-hydroxy-7-oxochol-5-enoic acid and 5,6-EC and 3β,5α,6β-triol to 3β,5α,6β-trihydroxycholanoic acid. Identification of intermediate metabolites is facilitated by their unusual MSn fragmentation patterns. Semi-quantitative measurements are possible, but absolute values await the synthesis of isotope-labelled standards.
published_date 2018-06-01T03:49:59Z
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score 11.013148

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