title: Substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase.
abstract: In this study, we examined the substrate specificity and inhibitor sensitivity of rabbit 20α-hydroxysteroid dehydrogenase (AKR1C5), which plays a role in the termination of pregnancy by progesterone inactivation. AKR1C5 moderately reduced the 3-keto group of only 5α-dihydrosteroids with 17β- or 20α/β-hydroxy group among 3-ketosteroids. In contrast, the enzyme reversibly and efficiently catalyzed the reduction of various 17- and 20-ketosteroids, including estrogen precursors (dehydroepiandrosterone, estrone and 5α-androstan-3β-ol-17-one) and tocolytic 5β-pregnane-3,20-dione. In addition to the progesterone inactivation, the formation of estrogens and metabolism of the tocolytic steroid by AKR1C5 may be related to its role in rabbit parturition. AKR1C5 also reduced various non-steroidal carbonyl compounds, including isatin, an antagonist of the C-type natriuretic peptide receptor, and 4-oxo-2-nonenal, suggesting its roles in controlling the bioactive isatin and detoxification of cytotoxic aldehydes. AKR1C5 was potently and competitively inhibited by flavonoids such as kaempferol and quercetin, suggesting that its activity is affected by ingested flavonoids.
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.forename: Yuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kitade
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Bunai
authors.forename: Ossama
authors.initials: O
authors.lastname: El-Kabbani
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006914:Hydroxysteroids / Q000378:metabolism; D007510:Isatin / Q000378:metabolism; D007659:Ketones / Q000378:metabolism; D007664:Ketosteroids / Q000378:metabolism; D011809:Quinones / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D000447:Aldehydes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006914:Hydroxysteroids; D007659:Ketones; D007664:Ketosteroids; D011809:Quinones; D011994:Recombinant Proteins; D015262:Xenobiotics; D007510:Isatin; D043607:20-alpha-Hydroxysteroid Dehydrogenase