Metabolism of 32-hydroxylated 24,25-dihydrolanosterols by partially purified cytochrome P-45014DM from rat liver microsomes.
- 1 January 1988
- journal article
- research article
- Published by Pharmaceutical Society of Japan in CHEMICAL & PHARMACEUTICAL BULLETIN
- Vol. 36 (8), 3049-3054
- https://doi.org/10.1248/cpb.36.3049
Abstract
Metabolism of 32-hydroxylated 24,25-dihydrolanosterols (1-3), including the intermediate of lanosterol and 24,25-dihydrolanosterol (4, DHL) demethylation, were studied in a reconstituted system consisting of rat liver partially purified cytochrome P-450, which catalyzes lanosterol 14-demethylation (cytochrome P-45014DM), and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase. The reconstituted system converted lanost-8-en-3.beta.,32-diol (1) to 4,4-dimethyl-5.alpha.-cholesta-8,14-dien-3.beta.-ol (5), the 14-dehydroxymethylated product, in the same way as 4. Lanost-7-ene-3.beta.,32-diol (2) and lanost-6-ene-3.beta.,32-diol (3), the isomers of 1, were not converted to the corresponding 14-dehydroxymethylated products. The apparent Km value of cytochrome P-45014DM for 1 was about 1/6 of that for 4. The metabolism of 4 was inhibited by 7-oxo-24,25-dihydrolanosterol (6, 7-oxo-DHL), which is a potent inhibitor of cholesterol biosynthesis from lanosterol or 4. However, the metabolism of 1 was less inhibited by 6 than that of 4.This publication has 11 references indexed in Scilit:
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