DIFFERENT SUBSTRATE SPECIFICITIES OF LANOSTEROL 14-ALPHA-DEMETHYLASE (P-45014DM) OF SACCHAROMYCES-CEREVISIAE AND RAT-LIVER FOR 24-METHYLENE-24,25-DIHYDROLANOSTEROL AND 24,25-DIHYDROLANOSTEROL

The purified lanosterol 14α-demethylase (P-45014DM) of S. cerevisiae catalyzed the 14α-demethylation of 24-methylene-24,25-dihydrolanosterol (24-methylenelanost-8-en-3β-ol, 24-methylene-DHL), the natural substrate of the demethylase of filamentous fungi, as well as its natural substrate, lanosterol. Lanosterol 14α-demethylase of rat liver microsomes also catalyzed the 14α-demethylation of 24-methylene-DHL, but the activity was considerably lower than that for lanosterol. The activity of the rat liver enzyme for 24-methylene-DHL was also lower than that for 24,25-dihydrolanosterol (DHL), while the activity of yeast P-45014DM for 24-methylene-DHL was considerably higher than that for DHL. Since 24-substituted sterols are not found in mammals and DHL is not an intermediate of ergosterol biosynthesis by yeast, above-mentioned different substrate specificities between the yeast and the mammalian 14α-demethylases may reflect certain evolutional alteration in their active sites in relation to the difference in their sterol biosynthetic pathways. © 1991.