Studies on the 14 alpha-demethylation mechanism in cholesterol biosynthesis

Eur J Biochem. 1980 Sep;110(1):93-105. doi: 10.1111/j.1432-1033.1980.tb04844.x.

Abstract

Identification of radioactive 5 alpha-cholest-8(14)-ene-3 beta,7 alpha-diol in extracts obtained from incubations of 3 beta-hydroxy-5 alpha-[7-3H]cholest-7-ene-14 alpha-carbaldehyde with rat liver microsomes is reported. Levels of this diol in incubations of the 14 alpha-[32-3H]carbaldehyde were measured by multiple selected ion monitoring and were found to be of the same order of those of [3H]formate released from the substrate during the removal of the C-32 atom. The results demonstrate that the diol does not originate from known intermediates of cholesterol biosynthesis, i.e. 5 alpha-cholesta-7,14-dien-3 beta-ol, 5 alpha-cholest-7-en-3 beta-ol and from 5 alpha-cholest-8(14)-en-3 beta-ol. Functionalization at position 7 in the metabolism of 3 beta-hydroxy-5 alpha-cholest-7-ene-14 alpha-carbaldehyde suggests the direct involvement of the double bond in the elimination of the 14 alpha-formyl group in the biosynthetic pathway from lanosterol to cholesterol. 5 alpha-Cholest-8(14)-en-3 beta-ol appears not to be involved in the metabolism of the 14 alpha-carbaldehyde.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Animals
  • Chemical Phenomena
  • Chemistry
  • Cholestenes / metabolism
  • Cholesterol / biosynthesis*
  • Dealkylation
  • Gas Chromatography-Mass Spectrometry
  • Microsomes, Liver / metabolism*
  • Rats

Substances

  • Cholestenes
  • 3-hydroxycholest-7-ene-14-carbaldehyde
  • cholest-8(14)-ene-3,7-diol
  • Cholesterol