Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

David W. Crabb, Michinaga Matsumoto, David Chang, Min You

Research output: Contribution to journalArticle

300 Citations (Scopus)

Abstract

Alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of ethanol consumed as part of the diet and their activities contribute to 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 pathophysiological 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 expressed either in the cells generating it, or by delivery of acetaldehyde 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, fetal 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. It will be important to replicate other interesting associations between these variants and other cancers and heart disease, and to determine the biochemical mechanisms underlying the associations.

Original languageEnglish (US)
Pages (from-to)49-63
Number of pages15
JournalProceedings of the Nutrition Society
Volume63
Issue number1
DOIs
StatePublished - Feb 1 2004

Fingerprint

aldehyde dehydrogenase
Aldehyde Dehydrogenase
Acetaldehyde
Alcohol Dehydrogenase
alcohol dehydrogenase
acetaldehyde
Ethanol
alcohols
ethanol
Alcohols
Pathology
alcohol abuse
neoplasms
fetal alcohol syndrome
Pharyngeal Neoplasms
Genes
gout
Fetal Alcohol Spectrum Disorders
religion
Gene-Environment Interaction

Keywords

  • Alcohol dehydrogenase
  • Aldehyde dehydrogenase
  • Cancer
  • Liver

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. / Crabb, David W.; Matsumoto, Michinaga; Chang, David; You, Min.

In: Proceedings of the Nutrition Society, Vol. 63, No. 1, 01.02.2004, p. 49-63.

Research output: Contribution to journalArticle

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