Enzymatic properties of a member (AKR1C20) of the aldo-keto reductase family

Abstract

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 Km values for testosterone and 5α-dihydrotestosterone were high (>0.2 mM), those for 3α-hydroxy- and 3-keto-steroids were low (0.3-5 μM), resulting in high catalytic efficiency for the substrates. Although no significant dehydrogenase activity towards nonsteroidal 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. © 2006 Pharmaceutical Society of Japan.