Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

[en] Acetaldehyde, the first product of ethanol metabolism, has been speculated to be involved in many pharmacological and behavioral effects of ethanol. In particular, acetaldehyde has been suggested to contribute to alcohol abuse and alcoholism. In the present paper, we review current data on the role of acetaldehyde and ethanol metabolism in alcohol consumption and abuse. Ethanol metabolism involves several enzymes. Whereas alcohol dehydrogenase metabolizes the bulk of ethanol within the liver, other enzymes, such as cytochrome P4502E1 and catalase, also contributes to the production of acetaldehyde from ethanol oxidation. In turn, acetaldehyde is metabolized by the enzyme aldehyde dehydrogenase. In animal studies, acetaldehyde is mainly reinforcing particularly when injected directly into the brain. In humans, genetic polymorphisms of the enzymes alcohol dehydrogenase and aldehyde dehydrogenase are also associated with alcohol drinking habits and the incidence of alcohol abuse. From these human genetic studies, it has been concluded that blood acetaldehyde accumulation induces unpleasant effects that prevent further alcohol drinking. It is therefore speculated that acetaldehyde exerts opposite hedonic effects depending on the localization of its accumulation. In the periphery, acetaldehyde is primarily aversive, whereas brain acetaldehyde is mainly reinforcing. However, the peripheral effects of acetaldehyde might also be dependent upon its peak blood concentrations and its rate of accumulation, with a narrow range of blood acetaldehyde concentrations being reinforcing.

Research Center/Unit :

Centre de Neurosciences Cognitives et Comportementales - ULiège

Disciplines :

Neurosciences & behavior
Psychiatry
Biochemistry, biophysics & molecular biology

Author, co-author :

Quertemont, Etienne ; Université de Liège - ULiège > Département des sciences cognitives > Psychologie quantitative

Language :

English

Title :

Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

Publication date :

2004

Journal title :

Molecular Psychiatry

ISSN :

1359-4184

eISSN :

1476-5578

Publisher :

Nature Publishing Group, Houndmills, United Kingdom

Volume :

Issue :

Pages :

570-581

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

since 27 November 2008

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