Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders.
Biotransformation
Cholestanols
/ blood
Cholesterol
/ blood
Cholic Acids
/ biosynthesis
Chromatography, Liquid
Epoxide Hydrolases
/ blood
Free Radicals
/ blood
Humans
Hydroxycholesterols
/ blood
Hydroxylation
Ketocholesterols
/ blood
Lysosomal Storage Diseases
/ blood
Mass Spectrometry
Niemann-Pick Diseases
/ blood
Oxidation-Reduction
Wolman Disease
/ blood
Wolman Disease
Bile acid and salts/biosynthesis
Cholesterol/metabolism
Free radical
Inborn errors of metabolism
Lipidomics
Mass spectrometry
Niemann-Pick disease
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
20 11 2019
20 11 2019
Historique:
received:
28
02
2019
revised:
12
04
2019
accepted:
16
04
2019
pubmed:
23
4
2019
medline:
8
9
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31009661
pii: S0891-5849(19)30330-2
doi: 10.1016/j.freeradbiomed.2019.04.020
pmc: PMC6863434
pii:
doi:
Substances chimiques
Cholestanols
0
Cholic Acids
0
Free Radicals
0
Hydroxycholesterols
0
Ketocholesterols
0
cholestane-3,5,6-triol
115510-05-9
cholest-5-en-3 beta,7 alpha-diol
566-26-7
Cholesterol
97C5T2UQ7J
Epoxide Hydrolases
EC 3.3.2.-
cholesterol-5 alpha,6 alpha-epoxide hydrase
EC 3.3.2.-
7-ketocholesterol
O7676FE78M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-133Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : Medical Research Council
ID : MR/N001427/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N015932/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/I001735/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL067773
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS081985
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Références
J Biol Chem. 2011 Sep 23;286(38):33021-8
pubmed: 21813643
Biochem Pharmacol. 2013 Jul 1;86(1):146-53
pubmed: 23415904
J Lipid Res. 2011 Jul;52(7):1435-45
pubmed: 21518695
Annu Rev Biochem. 2003;72:137-74
pubmed: 12543708
Curr Opin Pharmacol. 2012 Dec;12(6):696-703
pubmed: 22917620
J Biol Chem. 2000 Sep 8;275(36):27627-33
pubmed: 10869358
Vitam Horm. 1999;57:249-324
pubmed: 10232052
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):E9346-E9355
pubmed: 29078321
Sci Transl Med. 2016 May 4;8(337):337ra63
pubmed: 27147587
Anal Bioanal Chem. 2015 Jul;407(17):5235-9
pubmed: 25796527
Curr Opin Clin Nutr Metab Care. 2018 Mar;21(2):90-96
pubmed: 29227331
Clin Chim Acta. 2016 Apr 1;455:39-45
pubmed: 26790753
J Lipid Res. 2016 Mar;57(3):361-7
pubmed: 26733147
Lipids. 2001 Jul;36(7):701-11
pubmed: 11521968
FEBS Lett. 2016 Jun;590(11):1651-62
pubmed: 27139891
Sci Transl Med. 2010 Nov 3;2(56):56ra81
pubmed: 21048217
J Lipid Res. 2001 Oct;42(10):1571-7
pubmed: 11590212
Clin Biochem. 2015 Jun;48(9):596-602
pubmed: 25819840
Physiol Rev. 2000 Jan;80(1):361-554
pubmed: 10617772
J Lipid Res. 2015 Oct;56(10):1926-35
pubmed: 26239048
Mol Biosyst. 2009 May;5(5):529-41
pubmed: 19381367
Free Radic Biol Med. 2007 Sep 1;43(5):695-701
pubmed: 17664133
J Clin Invest. 1998 Nov 1;102(9):1690-703
pubmed: 9802883
J Biol Chem. 2002 Jan 11;277(2):1128-38
pubmed: 11673457
Dev Cell. 2013 Aug 26;26(4):346-57
pubmed: 23954590
Biochem Pharmacol. 1968 Jul;17(7):1189-96
pubmed: 5659768
J Steroid Biochem Mol Biol. 2019 Jun;190:19-28
pubmed: 30902677
Biochem Biophys Res Commun. 2014 Apr 11;446(3):681-6
pubmed: 24406163
J Lipid Res. 2014 Feb;55(2):338-43
pubmed: 24190732
Biochimie. 2013 Mar;95(3):448-54
pubmed: 23111110
Cell Mol Life Sci. 2004 Apr;61(7-8):992-9
pubmed: 15095019
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12163-8
pubmed: 25092323
Biochem Pharmacol. 2013 Jul 1;86(1):3-14
pubmed: 23395696
J Lipid Res. 2005 Sep;46(9):2029-32
pubmed: 16103133
J Am Chem Soc. 2016 Jun 8;138(22):6932-5
pubmed: 27210001
J Pharmacol Exp Ther. 1968 Feb;159(2):399-408
pubmed: 4966293
J Biol Chem. 2004 Apr 30;279(18):18415-24
pubmed: 14973125
Chem Phys Lipids. 2017 Oct;207(Pt B):69-80
pubmed: 28411018
Nat Commun. 2013;4:1840
pubmed: 23673625
J Biol Chem. 2008 Jun 6;283(23):15521-5
pubmed: 18285330
J Lipid Res. 2018 Jun;59(6):1058-1070
pubmed: 29626102
Atherosclerosis. 1999 Jan;142(1):1-28
pubmed: 9920502
J Lipid Res. 2011 Jun;52(6):1117-27
pubmed: 21411718
J Lipid Res. 2010 Nov;51(11):3299-305
pubmed: 20671299
J Lipid Res. 2014 Jun;55(6):1165-72
pubmed: 24771866
Clin Chem. 2015 Feb;61(2):400-11
pubmed: 25512642
Mol Cell. 2018 Oct 18;72(2):316-327.e5
pubmed: 30340023