Rat genes, akr1c19 and RGD1564865, encode members (R1C19 and 20HSDL, respectively) of the aldo-keto reductase (AKR) 1C subfamily, whose functions, however, remain unknown. Here, we show that recombinant R1C19 and 20HSDL exhibit NAD⁺-dependent dehydrogenase activity for prostaglandins (PGs) with 9α-hydroxy group (PGF_2α, its 13,14-dihydro- and 15-keto derivatives, 9α,11β-PGF₂ and PGD₂). 20HSDL oxidized the PGs with much lower K_m (0.3–14 μM) and higher k_cat/K_m values (0.064–2.6 min⁻¹μM⁻¹) than those of R1C19. They also differed in other properties: R1C19, but not 20HSDL, oxidized some 17β-hydroxysteroids (5β-androstane-3α,17β-diol and 5β-androstan-17β-ol-3-one). 20HSDL was specifically inhibited by zomepirac, but not by R1C19-selective inhibitors (hexestrol, flavonoids, ibuprofen and flufenamic acid), although the two enzymes were sensitive to indomethacin and cis-unsaturated fatty acids. The mRNA for 20HSDL was expressed abundantly in rat kidney and at low levels in the liver, testis, brain, heart and colon, in contrast to ubiquitous expression of R1C19 mRNA. The comparison of enzymic features of R1C19 and 20HSDL with rat PG dehydrogenases and other AKRs suggests not only a close relationship of 20HSDL with 9-hydroxy-PG dehydrogenase in rat kidney, but also roles of R1C19 and rat AKRs (1C16 and 1C24) in the metabolism of PGF_2α, PGD₂ and 9α,11β-PGF₂ in other tissues.

大鼠基因akr1c19和RGD1564865编码醛基酮还原酶（AKR）1C亚家族的成员（分别为R1C19和20HSDL），但其功能尚不清楚。在这里，我们表明，重组R1C19和20HSDL展览NAD ⁺依赖的脱氢酶为前列腺素（PGs）合成具有9α-羟基（PGF活性_2α，其13,14-二氢-和15-酮衍生物，9α，11β-PGF ₂和PGD ₂）。20HSDL氧化具有低得多的PGS的ķ_米（0.3-14μM）和更高ķ_猫/ ķ_米值（0.064-2.6分钟^-1 μM ^-1），而不是R1C19。它们的其他性质也有所不同：R1C19而非20HSDL氧化了一些17β-羟基类固醇（5β-雄甾烷3α，17β-二醇和5β-雄甾烷17β-醇-3-酮）。尽管zomepirac对20HSDL有特异性抑制作用，但对R1C19选择性抑制剂（己烯雌酚，类黄酮，布洛芬和氟苯那酸）没有特异性抑制作用，尽管这两种酶对消炎痛和顺式敏感-不饱和脂肪酸。与R1C19 mRNA的普遍表达相反，20HSDL的mRNA在大鼠肾脏中大量表达，而在肝脏，睾丸，大脑，心脏和结肠中则低表达。R1C19和20HSDL与大鼠PG脱氢酶和其他AKR的酶学特征的比较不仅表明20HSDL与9-羟基-PG脱氢酶在大鼠肾脏中具有密切的关系，而且R1C19和大鼠AKR（1C16和1C24）在大鼠肾脏中的作用也很密切。 PGF的代谢_2α，PGD ₂和9α，11β-PGF ₂在其它组织中。