Evidence for the contribution of a sterol 14-reductase to the 14 alpha-demethylation of lanosterol by yeast.
Lanosterol was converted to a 14-demethylated metabolite, 4,4-dimethylzymosterol by Saccharomyces cerevisiae microsomes. This metabolism was mediated by a cytochrome P-450 (P-450/14DM). However, a reconstituted system consisting of P-450/14DM and its reductase converted lanosterol to the 14-desaturated derivative of 4,4-dimethylzymosterol, 4,4-dimethyl-5 alpha-cholesta-8, 14,24-trien-3 beta-ol (trienol). When AY-9944 was added to the reaction system with the microsomes, the trienol was formed with corresponding decrease in 4,4-dimethylzymosterol. These observations indicate that the 14 alpha-demethylation of lanosterol by yeast microsomes occurs sequentially via the trienol. Reduction of the trienol to 4,4-dimethylzymosterol is mediated by an AY-9944-sensitive reductase.
Y
Y
Aoyama
Y
Y
Yoshida
D003510:Cyclohexanes / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007810:Lanosterol / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D010088:Oxidoreductases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride / Q000494:pharmacology*
D003510:Cyclohexanes; D007810:Lanosterol; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C022672:delta(14)-sterol reductase