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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 / William, Griffiths

The Journal of Steroid Biochemistry and Molecular Biology, Volume: 195, Start page: 105475

Swansea University Author: William, Griffiths

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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...

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Published in: The Journal of Steroid Biochemistry and Molecular Biology
ISSN: 09600760
Published: 2019
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa51994
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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.
Keywords: 24S-hydroxycholesterol, 24S,25-epoxycholesterol, CYP46A1, bile acid biosynthesis, deuterium-enrichment, deuterium-isotope effect, liquid chromatography – mass spectrometry, derivatisation
College: Swansea University Medical School
Start Page: 105475