Studies on the 14α‐Demethylation Mechanism in Cholesterol Biosynthesis

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Abstract
Identification of radioactive 5α-cholest-8(14)-ene-3β,7α-diol in extracts obtained from incubations of 3β-hydroxy-5α-[7-3H]cholest-7-ene-14α-carbaldehyde with rat liver microsomes is reported. Levels of this diol in incubations of the 14α-[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. 5α-cholesta-7,14-dien-3β-ol, 5α-cholest-7-en-3β-ol and from 5α-cholest-8(14)-en-3β-ol. Functionalization at position 7 in the metabolism of 3β-hydroxy-5α-cholest-7-ene-14α-carbaldehyde suggests the direct involvement of the double bond in the elimination of the 14α-formyl group in the biosynthetic pathway from lanosterol to cholesterol. 5α-Cholest-8(14)-en-3β-ol appears not to be involved in the metabolism of the 14α-carbaldehyde.