Kinetic Analysis of Reversible Inhibition of 16α-Hydroxyandrostenedione Aromatization in Human Placental Microsomes by Suicide Substrates of Androstenedione Aromatization
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概要
- 論文の詳細を見る
To gain insight into the catalytic function of aromatase and its substrate specificity, we studied reversible inhibition of 16α-hydroxyandrostenedione (16α-OHAD) aromatization in human piacental 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 10β-acetoxyandrost-5-en-7,17-dione (5) that, in contrast, do not cause a suicide inactivation of 16α-OHAD aromatization. All inhibitors examined blocked 16α-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 16α-OHAD aromatization experiments were markedly different from those obtained in the AD aromatization experiments. The results predict that all inhibitors examined bind to the 16α-OHAD binding site in a manner that does not cause suicide inactivation of 16α-OHAD aromatization. These findings would be useful for understanding the active (binding) site structure as well as the catalytic function of aromatase.
- 社団法人日本薬学会の論文
- 2003-06-01
著者
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Yoshimura A
Tohoku Pharmaceutical University
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Yoshimura Akiko
Tohoku Pharmaceutical University
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Yoshimura Akiko
Tohoku College Of Pharmacy
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NUMAZAWA Mitsuteru
Tohoku College of Pharmacy
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MUTSUMI Ayako
Tohoku Pharmaceutical University
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TACHIBANA Mii
Tohoku Pharmaceutical University
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Tachibana M
Tohoku Pharmaceutical University
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Tachibana Mii
Tohoku College Of Pharmacy
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Mutsumi A
Tohoku Pharmaceutical University
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Numazawa Mitsuteru
Tohoku Pharmaceutical University
関連論文
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