Active site-directed irreversible inhibition of 3 beta-hydroxysteroid dehydrogenase from human placenta.
To obtain a placental microsome preparation able to convert androstenedione and testosterone specifically to estrogens, 3 beta-hydroxysteroid dehydrogenase must be eliminated. After solubilisation by Triton X-100, the remaining 3 beta-hydroxysteroid dehydrogenase activity is inhibited by 11 alpha-bromoacetoxyprogesterone, an alkylating analogue of progesterone, which behaves as an irreversible active site-directed inhibitor. The enzyme is protected against inactivation and alkylation by steroid and coenzyme substrates. The inhibition is specific to 3 beta-hydroxysteroid dehydrogenase and the estrogen synthetase (aromatase) activity contained in the preparation is not affected by this inhibitor.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000478:Alkylation; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D007700:Kinetics; D009243:NAD / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy
D006908:Hydroxyprogesterones; D009243:NAD; C005669:11 alpha-bromoacetoxyprogesterone; D003687:Dehydroepiandrosterone; D015096:3-Hydroxysteroid Dehydrogenases