摘要：AKR1C20, a member of the aldo-keto reductase (AKR) superfamily, found by mouse genomic analysis, exhibits the highest sequence identity (89%) with mouse liver 17β-hydroxysteroid dehydrogenase (HSD) type 5, but its function remains unknown. In this report, we have expressed the recombinant AKR1C20 from its cDNA, and examined its properties. The purified enzyme was a 36-kDa monomer, and showed both 17β-HSD and 3α-HSD activities in the presence of NADP(H) as the coenzymes. While the K m values for testosterone and 5α-dihydrotestosterone were high (>0.2 m M ), those for 3α-hydroxy- and 3-keto-steroids were low (0.3—5 μ M ), resulting in high catalytic efficiency for the substrates. Although no significant dehydrogenase activity towards non-steroidal alcohols was observed, the enzyme highly reduced α-dicarbonyl compounds such as 16-ketoestrone, 9,10-phenanthrenequinone, acenaphthenequinone, 1-phenylisatin and camphorquinone. The pH optima of the dehydrogenase and reductase activities were 10.5 and 6.5—7.5, respectively. The enzyme was inhibited by sulfobromophthalein, hexestrol, indomethacin and flufenamic acid. The properties of AKR1C20 are distinct from those of previously known mouse 17β-HSD type 5 (AKR1C6), 3α-HSD (AKR1C14) and other members of the AKR1C subfamily. Thus, AKR1C20 is a novel 3α(17β)-HSD, which may also function as a reductase for xenobiotic α-dicarbonyl compounds.
