Alcohol metabolism

Alcohol dehydrogenase (ADH) and mitochondria! aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of consumed ethanol . These enzymes also affect the rate of ethanol elimination from the blood. They are expressed at highest levels in liver, but at lower levels in many tissues. This pathway probably evolved as a detoxification mechanism for environmental alcohols.
However, with the consumption of large amounts of ethanol. the oxidation of ethanol can become a major energy source and. particularly in the liver, interferes with the metabolism of other nutrients. Polymorphic variants of the genes for these enzymes encode enzymes with altered kinetic properties.
The patho-physiological effects of these variants may be mediated by accumulation of acetaldehyde: High-activity ADH variants are predicted to increase the rate of acetaldehyde generation, while the low-activity ALDH2 variant is associated with an inability to metabolize this compound. The effects of acetaldehyde may be both in the cells, or by the acetaldehyde passing to various tissues by the bloodstream or even saliva.
Inheritance of the high-activity ADH β2. encoded by the ADH2*2 gene, and the inactive ALDH2*2 gene product have been conclusively associated with reduced risk of alcoholism. This association is influenced by gene-environment interactions, such as religion and national origin.
The variants have also been studied for association with alcoholic liver disease, cancer, foetal alcohol syndrome. CVD, gout, asthma and clearance of xenobiotics. The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus.
Crabb et al 2004, Proceedings of the Nutrition Society (2004) vol 63, 49-63

Martin Eastwood
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