Citation

Numazawa M, Mutsumi A, Tachibana M, Yoshimura A. Biol. Pharm. Bull. 2003; 26(6): 890-892.

Copyright

(Copyright © 2003, Pharmaceutical Society of Japan)

DOI

10.1248/bpb.26.890

PMID

12808307

Abstract

To gain insight into the catalytic function of aromatase and its substrate specificity, we studied reversible inhibition of 16alpha-hydroxyandrostenedione (16alpha-OHAD) aromatization in human placental microsomes by several suicide substrates of androstenedione (AD) aromatization, including 4-hydroxyAD (1), 6-oxoAD (2) and its 19-hydroxy analogue 3, androst-5-ene-4,7,17-trione (4), and 10beta-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a suicide inactivation of 16alpha-OHAD aromatization. All inhibitors examined blocked 16alpha-OHAD aromatization in a competitive manner with apparent K(i) values ranging from 0.50 to 980 nM. The relative K(i) values between inhibitors 1-5 obtained in the 16alpha-OHAD aromatization experiments were markedly different from those obtained in the AD aromatization experiments. The results predict that all inhibitors examined bind to the 16alpha-OHAD binding site in a manner that does not cause suicide inactivation of 16alpha-OHAD aromatization. These findings would be useful for understanding the active (binding) site structure as well as the catalytic function of aromatase.

Language: en

Keywords

Androstenedione; Aromatase; Aromatase Inhibitors; Binding Sites; Binding, Competitive; Catalysis; Enzyme Inhibitors; Humans; In Vitro Techniques; Kinetics; Microsomes; Placenta; Substrate Specificity