Interaction of 17 α-hydroxylase, 17(20)-lyase (CYP17A1) inhibitors - abiraterone and galeterone - with human sterol 14α-demethylase (CYP51A1).

Interaction of 17α-hydroxylase, 17(20)-lyase (CYP17A1) inhibitors - abiraterone and galeterone - with human sterol 14α-demethylase (CYP51A1).
J Inorg Biochem. 2018 May 21;186:24-33
Authors: Masamrekh R, Kuzikov A, Veselovsky A, Toropygin I, Shkel T, Strushkevich N, Gilep A, Usanov S, Archakov A, Shumyantseva V
Abstract
Abiraterone and galeterone induce type I differential spectral changes in human sterol 14α-demethylase (cytochrome P450 51A1, CYP51A1) with the sigmoidal shape of the binding curve. After approximation of the data by Hill model, the half-saturation concentrations (K0.5) were estimated as 22 ± 1 μM and 16 ± 1 μM and the Hill coefficients as 2.4 ± 0.2 and 1.97 ± 0.23 for abiraterone and galeterone, respectively. We analyzed the catalytic activity of CYP51A1 towards abiraterone and galeterone using an electrochemical system based on recombinant CYP51A1 immobilized on the screen-printed graphite electrode (SPE) modified by didodecyldimethylammonium bromide (DDAB) film. The study revealed the amperometric response of CYP51A1 upon addition of abiraterone, which may indicate the substrate properties of abiraterone towards CYP51A1. Galeterone caused negligible amperometric response of CYP51A1. Mass-spectrometric analysis of the products of CYP51A1-dependent electrocatalytic reaction at a controlled potential towards abiraterone and galeterone revealed products with m/z of 366.3 and 405.2, respectiv...

Source: Journal of Inorganic Biochemistry - May 21, 2018 Category: Biochemistry Authors: Masamrekh R, Kuzikov A, Veselovsky A, Toropygin I, Shkel T, Strushkevich N, Gilep A, Usanov S, Archakov A, Shumyantseva V Tags: J Inorg Biochem Source Type: research