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

  • M. Hellgren
  • P. Strömberg
  • O. Gallego
  • S. Martras
  • J. Farrés
  • B. Persson
  • X. Parés
  • J. -O. Höög
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

Copyright information

© Birkhäuser Verlag, Basel 2007

Authors and Affiliations

  • M. Hellgren
    • 1
  • P. Strömberg
    • 1
    • 5
  • O. Gallego
    • 2
    • 6
  • S. Martras
    • 2
  • J. Farrés
    • 2
  • B. Persson
    • 3
    • 4
  • X. Parés
    • 2
  • J. -O. Höög
    • 1
  1. 1.Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden
  2. 2.Department of Biochemistry and Molecular BiologyUniversitat Autònoma de BarcelonaBellaterra, BarcelonaSpain
  3. 3.IFM BioinformaticsLinköping UniversityLinköpingSweden
  4. 4.Department of Cell and Molecular BiologyKarolinska InstitutetStockholmSweden
  5. 5.AstraZeneca R&DSödertäljeSweden
  6. 6.EMBLHeidelbergGermany