Possible Participation of Cytochrome P-450 in Cholesterol Synthesis

Abstract

Participation of cytochrome P-450 in cholesterol synthesis by rat liver postmito-chondrial fractions was examined since cholesterol is synthesized by a series of reactions, including certain microsomal ones, which require both NADPH and molecular oxygen.
Cholesterol synthesis from various precursors, namely acetate, mevalonate or squalene, was inhibited by carbon monoxide and was accelerated with liver preparations from the phenobarbital-treated rats as compared with those from the untreated rats. This dif-ference in rate was much more significant with mevalonate as precursor than with acetate, and greater with squalene than with mevalonate. The addition to the reaction mixture of drugs, which were metabolized by enzyme systems involving cytochrome P-450, in-hibited the cholesterol synthesis. From these results, it is probable that cytochrome P-450 is functional in cholesterol synthesis.