Metabolism of 32-oxo-24,25-dihydrolanosterols by partially purified cytochrome P-450(14DM) from rat liver microsomes.
Metabolism of 32-oxo-24,25-dihydrolanosterols (3 beta-hydroxylanost-8-en-32- al (4,delta 8-CHO) and 3 beta-hydroxylanost-7-en-32-al (5,delta 7-CHO)) was studied in a reconstituted system consisting of rat liver partially purified cytochrome P-450, which catalyzes lanosterol 14-demethylation (P-450(14DM)), and reduced nicotineamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase. The reconstituted system converted delta 8-CHO to 4,4-dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol (2, 8, 14-Diene), which corresponds to the 14-deformylated product. delta 7-CHO, the isomer of delta 8-CHO, was not converted to the corresponding 14-deformylated product. The apparent Km value of cytochrome P-450(14DM) for delta 8-CHO was about 1/20 of that for 24,25-dihydrolanosterol (1, DHL). The metabolism of delta 8-CHO was inhibited by 7-oxo-24,25-dihydrolanosterol (6, 7-oxo-DHL), which is a potent inhibitor of cholesterol biosynthesis from lanosterol or DHL. However, the metabolism of delta 8-CHO was less inhibited by 7-oxo-DHL than that of DHL.
Sonoda
Y
Y
Sekigawa
Y
Y
Sato
Y
Y
D000818:Animals; 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
C062857:3-hydroxylanost-7-en-32-al; D007810:Lanosterol; C032444:lanosten-3-ol-32-al; D003577:Cytochrome P-450 Enzyme System