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 Km values ranged from 0.05 to 0.3 μM and kcat 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 Km 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.
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Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007
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Hellgren, M., Strömberg, P., Gallego, O. et al. Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism. Cell. Mol. Life Sci. 64, 498 (2007). https://doi.org/10.1007/s00018-007-6449-8
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DOI: https://doi.org/10.1007/s00018-007-6449-8