title: Enzymatic properties of a member (AKR1C19) of the aldo-keto reductase family.
abstract: A member (AKR1C19) of the aldo-keto reductase (AKR) superfamily, found by mouse genomic analysis, was shown to be highly expressed in the liver and gastrointestinal tract, but its function remains unknown. In this study, the recombinant AKR1C19 was expressed and purified to homogeneity. The enzyme was a 36-kDa monomer, and reduced alpha-dicarbonyl compounds such as camphorquinone and isatin using both NADH and NADPH as the coenzymes. Although apparent kinetic constants for the two coenzymes were similar, the NADPH-linked activity was potently inhibited by submillimolar concentrations of NAD+, but the inhibition of the NADH-linked activity was not significant, suggesting that the enzyme exhibits the NADH-linked reductase activity in vivo. AKR1C19 slowly oxidized 3-hydroxyhexobarbital, S-indan-1-ol and cis-benzene dihydrodiol, but was inactive towards steroids, prostaglandins, monosaccharides, and other xenobiotic alcohols. In addition, the enzyme was inhibited only by dicumarol, lithocholic acid and genistein of various compounds tested. Thus, AKR1C19 possesses properties distinct from other members of the AKR superfamily, and may function as a reductase for endogenous isatin and xenobiotic alpha-dicarbonyl compounds in the liver and gastrointestinal tract.
authors.affiliation: Laboratory of Biochemistry, Gifu Pharmaceutical University, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Ishikura
authors.forename: Kenji
authors.initials: K
authors.lastname: Horie
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sanai
authors.forename: Kengo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D011994:Recombinant Proteins; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse