title: Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism.
abstract: The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K(m) values ranged from 0.05 to 0.3 microM and k(cat) values from 2.3 to 17.6 min(-1), while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K(m) values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Hellgren
authors.forename: P
authors.initials: P
authors.lastname: Strömberg
authors.forename: O
authors.initials: O
authors.lastname: Gallego
authors.forename: S
authors.initials: S
authors.lastname: Martras
authors.forename: J
authors.initials: J
authors.lastname: Farrés
authors.forename: B
authors.initials: B
authors.lastname: Persson
authors.forename: X
authors.initials: X
authors.lastname: Parés
authors.forename: J-O
authors.initials: JO
authors.lastname: Höög
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D051381:Rats; D016415:Sequence Alignment; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D014801:Vitamin A; D000426:Alcohol Dehydrogenase