title: Human dehydrogenase/reductase (SDR family) member 11 is a novel type of 17β-hydroxysteroid dehydrogenase.
abstract: We report characterization of a member of the short-chain dehydrogenase/reductase superfamily encoded in a human gene, DHRS11. The recombinant protein (DHRS11) efficiently catalyzed the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5α-androstanes into their 17β-hydroxyl metabolites with NADPH as a coenzyme. In contrast, it exhibited reductive 3β-hydroxysteroid dehydrogenase activity toward 5β-androstanes, 5β-pregnanes, 4-pregnenes and bile acids. Additionally, DHRS11 reduced α-dicarbonyls (such as diacetyl and methylglyoxal) and alicyclic ketones (such as 1-indanone and loxoprofen). The enzyme activity was inhibited in a mixed-type manner by flavonoids, and competitively by carbenoxolone, glycyrrhetinic acid, zearalenone, curcumin and flufenamic acid. The expression of DHRS11 mRNA was observed widely in human tissues, most abundantly in testis, small intestine, colon, kidney and cancer cell lines. Thus, DHRS11 represents a novel type of 17β-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution.
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan. Electronic address: sendo@gifu-pu.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Namiki
authors.initials: N
authors.lastname: Miyagi
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Faculty of Engineering, Gifu University, Gifu 501-1193, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ikari
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D017398:Alternative Splicing; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007664:Ketosteroids / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007664:Ketosteroids; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009249:NADP; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; C000609588:DHRS11 protein, human
keywords: 17β-Hydroxysteroid dehydrogenase; 3β-Hydroxysteroid dehydrogenase; DHRS11; Dehydroepiandrosterone; Isolithocholic acid; Neurosteroid