Biosynthesis of Skin Sterols. Vi. Enzymatic Demethylation of Lanosterol and Lanosta-7,24-dien-3beta-ol by Homogenates of Rat Liver.

Lanosterol and lanosta-7,24-dien-3P-011 are biosynthesized by slices of rat skin (2). Lanosta-7,24-dien-30-01 was more highly labeled than lanosterol after a a-minute aerobic incubation of skin slices with labeled squalene (3). More labeled mevalonate was incorporated into the A7zt4 isomer than into the As,24 isomer when skin slices were incubated with arsenite (I). Lanosta7,24-dien-30-01 is not present in detectable amounts in the skin of normal rats; however, Clayton, Nelson, and Frantz (4) reported that more than 2 times as much lanosta-7,24-dien-3P-ol as lanosterol was isolated from rat skin when the later stages of sterol biosynthesis were inhibited with dietary triparanol. The relative amounts of the A7824 and A*J4 isomers that accumulate during various treatments may indicate the relative contribution of each sterol to the biosynthesis of skin sterols. However, the relative amounts of these sterol intermediates may be influenced markedly by their rates of subsequent conversion to products (CST-sterols). Accordingly, the rates of conversion of lanosterol and lanosta-7,24-dien-30-01 to Cz7-sterols were investigated. Homogenates of rat skin, which convert substantial amounts of labeled precursors to cholesterol, have not been obtained. However, homogenates of rat liver convert lanosterol (5) and lanosta-7,24-dien-3/3-ol (2) to C&sterols. This report describes the rate of enzymatic demethylationz of the two isomers by homogenates of rat liver.