Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolismShow others and affiliations
2007 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 64, no 4, p. 498-505Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Springer, 2007. Vol. 64, no 4, p. 498-505
Keywords [en]
Alcohol dehydrogenase, computer modeling, kinetic constant, retinaldehyde, retinol, substrate docking
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-109973DOI: 10.1007/s00018-007-6449-8ISI: 000244565100010PubMedID: 17279314Scopus ID: 2-s2.0-33847322975OAI: oai:DiVA.org:oru-109973DiVA, id: diva2:1815975
2023-11-302023-11-302023-12-01Bibliographically approved