17-n-n-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one has been researched along with trilostane* in 2 studies
2 other study(ies) available for 17-n-n-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one and trilostane
| Article | Year |
|---|---|
Evidence for distinct dehydrogenase and isomerase sites within a single 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase protein.
Complementary DNA encoding human 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) has been expressed in transfected GH4C1 with use of the cytomegalovirus promoter. The activity of the expressed protein clearly shows that both dehydrogenase and isomerase enzymatic activities are present within a single protein. However, such findings do not indicate whether the two activities reside within one or two closely related catalytic sites. With use of [3H]-5-androstenedione, the intermediate compound in dehydroepiandrosterone (DHEA) transformation into 4-androstenedione by 3 beta-HSD, the present study shows that 4MA (N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide) and its analogues inhibit DHEA oxidation competitively while they exert a noncompetitive inhibition of the isomerization of 5-androstenedione to 4-androstenedione with an approximately 1000-fold higher Ki value. The present results thus strongly suggest that dehydrogenase and isomerase activities are present at separate sites on the 3 beta-HSD protein. In addition, using 5 alpha-dihydrotestosterone (DHT) and 5 alpha-androstane-3 beta, 17 beta-diol as substrates for dehydrogenase activity only, we have found that dehydrogenase activity is reversibly and competitively inhibited by 4MA. Such data suggest that the irreversible step in the transformation of DHEA to 4-androstenedione is due to a separate site possessing isomerase activity that converts the 5-ene-3-keto to a much more stable 4-ene-3-keto configuration. Topics: Androgen Antagonists; Androstane-3,17-diol; Azasteroids; Binding Sites; Binding, Competitive; Cell Line; Dehydroepiandrosterone; Dihydrotestosterone; Humans; Kinetics; Multienzyme Complexes; Placenta; Progesterone Reductase; Protein Conformation; Steroid Isomerases; Substrate Specificity; Tumor Cells, Cultured | 1991 |
Differential inhibition of dehydrogenase and 5-ene----4-ene isomerase activities of purified 3 beta-hydroxysteroid dehydrogenase. Evidence for two distinct sites.
The success in synthesis of [3H]5-androstene-3,17-dione, the intermediate product in the transformation of DHEA to 4-androstenedione by 3 beta-hydroxysteroid dehydrogenase/5-ene----4-ene isomerase (3 beta-HSD) offers the opportunity to determine whether or not the two activities reside in one active site or in two closely related active sites. The finding that N,N-dimethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) inhibits competitively and specifically the dehydrogenase activity whereas a non-competitive inhibition type with a Ki value 1000 fold higher was observed for the isomerase activity, indicated that dehydrogenase and isomerase activities belong to separate sites. Using 5 alpha-dihydro-testosterone and 5 alpha-androstane-3 beta, 17 beta-diol, exclusive substrates for dehydrogenase activity, it was shown that dehydrogenase is reversible and strongly inhibited by 4-MA and that thus the irreversible step in the transformation of DHEA to 4-androstenedione is due to the isomerase activity. Topics: 3-Hydroxysteroid Dehydrogenases; Androstenedione; Azasteroids; Binding Sites; Dehydroepiandrosterone; Dihydrotestosterone; Humans; In Vitro Techniques; Kinetics | 1991 |