[Heterologous expression of functionally active human cytochrome P-450s. Cytochrome P-450IIIA4 catalyzes the biotransformation of the anabolic steroid hormone methandrostenolone].
The expression of the cytochrome P450IIIA4 gene in the Saccharomyces cerevisiae yeast using the shuttle vector pYeDP1-8/2 has been carried out. The microsomal fraction isolated from the transformed yeast cells was used for biotransformation of the anabolic steroid hormone-methandrostenolone (MA). The microsomal oxidation products were analyzed by HPLC and two-dimensional TLC. It was shown that microsomes of the yeasts expressing human cytochrome P450IIIA4 catalyze the MA conversion into its 6 beta-hydroxy derivative. An identical product is formed via a reaction catalyzed by human liver microsomes. The use of the heterological system of cytochrome P450IIIA4 expression has made it possible to establish its role in MA metabolism. The experimental system simulates the first phase of the drug biotransformation in liver cells.
Krynetskiĭ
E Iu
EIu
Kovaleva
I E
IE
Luzikov
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VN
D001711:Biotransformation; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008696:Methandrostenolone / Q000493:pharmacokinetics*; D008861:Microsomes / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000235:genetics
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D008696:Methandrostenolone
Geterologicheskaia ékspressiia funktsional'no-aktivnykh tsitokhromov P-450 cheloveka. Tsitokhrom P-450IIIA4 kataliziruet biotransformatsiiu anabolicheskogo steroidnogo gormona metandrostenolona.