Chinese hamster monomeric carbonyl reductases of the short-chain dehydrogenase/reductase superfamily

Chinese hamster monomeric carbonyl reductases (CHCRs) belong to the short-chain dehydrogenase/reductase (SDR) superfamily, which is a family of enzymes that metabolize many endogenous and xenobiotic compounds. We previously cloned three carbonyl reductase cDNAs—Chcr1, Chcr2, and Chcr3. By performing spectrophotometric analyses, we indicated that the enzymes CHCR1, CHCR2, and CHCR3 had similar specificities toward steroids; only CHCR3 did not show any reactivity with prostaglandins (PGs). In the present study, we investigated the characteristics of CHCRs in detail, that is, the differences in their expression patterns, physicochemical properties, and enzymatic activities. CHCR1 exhibited sex-dependent expression patterns. CHCRs showed multiple surface potentials in the zeta potential analysis and CHCR3 exhibited an isatin reductase activity with a high Km value. By the present HPLC-analysis, all the three enzymes exhibited PGF2α dehydrogenase activity and could oxidize PGF2α to PGE2 and 15-keto-PGF2α, i.e., the three enzymes exhibited 9- and 15-hydroxy PG dehydrogenase activities. Moreover, 15-keto-PGE2 was detected in a comparatively higher amount in the dehydrogenase reaction products of CHCR2 than in those of CHCR1 and CHCR3, suggesting that CHCR2 can oxidize PGE2 and/or 15-keto-PGF2α to 15-keto-PGE2; however, these two PGs did not seem to be efficient substrates of CHCR1. Despite the differences in the dehydrogenase activities between CHCR1 and CHCR2, PGE2 reductase activities of the two enzymes were similar, and PGF2α was predominantly produced from PGE2 as a result of the PG 9-keto reductase activity. On the other hand, CHCR3 exhibited a reduced PGE2 reductase activity. In conclusion, although the CHCRs share a high degree of sequence identity (>70%), they clearly differed in their enzymatic characteristics.