Cellular and Molecular Life Sciences

, 64:498

Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism

Authors

  • M. Hellgren
    • Department of Medical Biochemistry and BiophysicsKarolinska Institutet
  • P. Strömberg
    • Department of Medical Biochemistry and BiophysicsKarolinska Institutet
    • AstraZeneca R&D
  • O. Gallego
    • Department of Biochemistry and Molecular BiologyUniversitat Autònoma de Barcelona
    • EMBL
  • S. Martras
    • Department of Biochemistry and Molecular BiologyUniversitat Autònoma de Barcelona
  • J. Farrés
    • Department of Biochemistry and Molecular BiologyUniversitat Autònoma de Barcelona
  • B. Persson
    • IFM BioinformaticsLinköping University
    • Department of Cell and Molecular BiologyKarolinska Institutet
  • X. Parés
    • Department of Biochemistry and Molecular BiologyUniversitat Autònoma de Barcelona
    • Department of Medical Biochemistry and BiophysicsKarolinska Institutet
Research Article

DOI: 10.1007/s00018-007-6449-8

Cite this article as:
Hellgren, M., Strömberg, P., Gallego, O. et al. Cell. Mol. Life Sci. (2007) 64: 498. doi:10.1007/s00018-007-6449-8

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.

Keywords.

Alcohol dehydrogenasecomputer modelingkinetic constantretinaldehyderetinolsubstrate docking
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Copyright information

© Birkhäuser Verlag, Basel 2007