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Formation and metabolism of oxysterols and cholestenoic acids found in the mouse circulation: Lessons learnt from deuterium-enrichment experiments and the CYP46A1 transgenic mouse
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Peter J. Crick,
Eylan Yutuc,
Jonas Abdel-Khalik,
Ahmed Saeed,
Christer Betsholtz,
Guillem Genove,
Ingemar Björkhem,
Yuqin Wang,
William Griffiths
The Journal of Steroid Biochemistry and Molecular Biology, Volume: 195, Start page: 105475
Swansea University Authors:
Eylan Yutuc , William Griffiths
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DOI (Published version): 10.1016/j.jsbmb.2019.105475
Abstract
While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol in the...
| Published in: | The Journal of Steroid Biochemistry and Molecular Biology |
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| ISSN: | 09600760 |
| Published: |
2019
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa51994 |
| Abstract: |
While the presence and abundance of the major oxysterols and cholestenoic acids in the circulation is well established, minor cholesterol metabolites may also have biological importance and be of value to investigate. In this study by observing the metabolism of deuterium-labelled cholesterol in the pdgfbret/ret mouse, a mouse model with increased vascular permeability in brain, and by studying the sterol content of plasma from the CYP46A1 transgenic mouse overexpressing the human cholesterol 24S-hydroxylase enzyme we have been able to identify a number of minor cholesterol metabolites found in the circulation, make approximate-quantitative measurements and postulate pathways for their formation. These “proof of principle” data may have relevance when using mouse models to mimic human disease and in respect of the increasing possibility of treating human neurodegenerative diseases with pharmaceuticals designed to enhance the activity of CYP46A1 or by adeno-associated virus delivery of CYP46A1. |
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| Keywords: |
24S-hydroxycholesterol, 24S,25-epoxycholesterol, CYP46A1, bile acid biosynthesis, deuterium-enrichment, deuterium-isotope effect, liquid chromatography – mass spectrometry, derivatisation |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Start Page: |
105475 |