The formation and reduction of the 14,15-double bond in cholesterol biosynthesis

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Abstract
It was shown that 100μg quantities of 4,4′-dimethyl[2-3H2]cholesta-8,14-dien-3β-ol (IIIa), tritiated cholesta-8,14-dien-3β-ol, 4,4′-dimethyl[2-3H2]cholesta-7,14-dien-3β-ol, dihydro[2-3H2]lanosterol and [24-3H]lanosterol were converted by a 10000g supernatant of rat liver homogenate into cholesterol in 17%, 54%, 6%, 9.5% and 24% yields respectively. From an incubation of dihydro[3α-3H]lanosterol with a rat liver homogenate in the presence of a trap up to 38% of the radioactivity was found to be associated with a fraction that was unambiguously shown to be 4,4′-dimethylcholesta-8,14-dien-3β-ol. Another related compound, 4,4′-dimethylcholesta-7,14-dien-3β-ol was also shown to be equally effective in its ability to trap compound (IIIa) from an incubation of dihydro[3α-3H]lanosterol. The mechanism of the further conversion of the compound (IIIa) into cholesterol occurred by the reduction of the 14,15-double bond and involved the addition of a hydrogen atom from the medium to C-15 and another from the 4-position of NADPH to C-14. Two possible mechanisms for the removal of the 14α-methyl group in sterol biosynthesis are discussed.