Metabolism of 24,25-dihydrolanosterol analogs by partially purified cytochrome P-450(14DM) from rat liver microsomes.
27-Nor-24,25-dihydrolanosterol (27-nor-DHL), 26,27-dinor-24,25- dihydrolanosterol (26,27-dinor-DHL), and 25,26,27-trinor-24,25-dihydrolanosterol (25,26,27-trinor-DHL), analogs of 24,25-dihydrolanosterol (DHL) which have no C-27 carbon, C-26,27 carbons and C-25,26,27 carbons, were converted to the corresponding 14-demethylated products using a reconstituted monooxygenase system from rat liver microsomes which contained cytochrome P-450(14DM) catalyzing lanosterol 14-demethylation and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase in the presence of NADPH and molecular oxygen. Each metabolite showed a relative retention time (RtR) of 0.72 with respect to each substrate in high-performance liquid chromatography (HPLC) on a reversed-phase column. Comparison of each gas chromatography-mass spectrum and RtR value with those of the metabolite of DHL, 4,4-dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol, indicated that the metabolites could be inferred to be 27-nor-4,4-dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol, 26,27-dinor-4,4- dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol, and 25,26,27-trinor-4,4-dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol. However, 24,25,26,27-tetranor- and 23,24,25,26,27-pentanor analogs of DHL and 20-iso-24,25-dihydrolanosterol were not metabolized by the reconstituted enzyme system.
Sonoda
Y
Y
Sekigawa
Y
Y
Sato
Y
Y
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D066298:In Vitro Techniques; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D007810:Lanosterol; C015316:lanostenol; D003577:Cytochrome P-450 Enzyme System