Metabolism of Non-Enzymatically Derived Oxysterols: Clues from sterol metabolic disorders

William J Griffiths, 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, Douglas F Covey, Daniel S Ory, Yuqin Wang

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)124-133
Number of pages10
JournalFree Radical Biology and Medicine
Publication statusPublished - 20 Nov 2019


  • 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


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