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

doi:https://doi.org/10.1007/s00018-007-6449-8

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

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

19 Citations (Scopus)

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 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. © 2007 Birkhäuser Verlag.

Original language	English
Pages (from-to)	498-505
Journal	Cellular and Molecular Life Sciences
Volume	64
DOIs	https://doi.org/10.1007/s00018-007-6449-8
Publication status	Published - 1 Feb 2007

Keywords

Alcohol dehydrogenase
Computer modeling
Kinetic constant
Retinaldehyde
Retinol
Substrate docking

Access to Document

https://doi.org/10.1007/s00018-007-6449-8

Fingerprint Dive into the research topics of 'Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism'. Together they form a unique fingerprint.

Cite this

@article{062ebed4030f43849f564be9152d7873,

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 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 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. {\textcopyright} 2007 Birkh{\"a}user Verlag.",

keywords = "Alcohol dehydrogenase, Computer modeling, Kinetic constant, Retinaldehyde, Retinol, Substrate docking",

author = "M. Hellgren and P. Str{\"o}mberg and O. Gallego and S. Martras and J. Farr{\'e}s and B. Persson and X. Par{\'e}s and H{\"o}{\"o}g, {J. O.}",

year = "2007",

month = feb,

day = "1",

doi = "https://doi.org/10.1007/s00018-007-6449-8",

language = "English",

volume = "64",

pages = "498--505",

}

TY - JOUR

T1 - Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism

AU - Hellgren, M.

AU - Strömberg, P.

AU - Gallego, O.

AU - Martras, S.

AU - Farrés, J.

AU - Persson, B.

AU - Parés, X.

AU - Höög, J. O.

PY - 2007/2/1

Y1 - 2007/2/1

N2 - 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 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. © 2007 Birkhäuser Verlag.

AB - 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 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. © 2007 Birkhäuser Verlag.

KW - Alcohol dehydrogenase

KW - Computer modeling

KW - Kinetic constant

KW - Retinaldehyde

KW - Retinol

KW - Substrate docking

U2 - https://doi.org/10.1007/s00018-007-6449-8

DO - https://doi.org/10.1007/s00018-007-6449-8

M3 - Article

VL - 64

SP - 498

EP - 505

ER -