Differential inhibition of dehydrogenase and 5-ene----4-ene isomerase activities of purified 3 beta-hydroxysteroid dehydrogenase. Evidence for two distinct sites

J Steroid Biochem Mol Biol. 1991;40(4-6):545-8. doi: 10.1016/0960-0760(91)90275-a.


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.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
  • Androstenedione / metabolism
  • Azasteroids / pharmacology
  • Binding Sites
  • Dehydroepiandrosterone / metabolism
  • Dihydrotestosterone / analogs & derivatives
  • Dihydrotestosterone / pharmacology
  • Humans
  • In Vitro Techniques
  • Kinetics


  • Azasteroids
  • Dihydrotestosterone
  • Androstenedione
  • Dehydroepiandrosterone
  • 5-androstene-3,17-dione
  • 17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one
  • 3-Hydroxysteroid Dehydrogenases
  • trilostane