Ethanol oxidizing enzymes: roles in alcohol metabolism and alcoholic liver disease

The elucidation of nucleotide and amino acid sequences of the genes and enzymes involved in the metabolism of ethanol has led to the ability to genotype individuals simply and rapidly. Although the different isozymes were once thought to be a likely explanation for between individual differences in alcohol elimination rates, this has not been found to be the case. Other explanations that remain to be investigated include potential regulatory variants in the genes that alter the level of expression of the enzymes, and genetic influences on activity of the malateaspartate shuttle and rates of mitochondrial NADH reoxidation. However, the isozymes encoded by ADH2*2 and ALDH2*2 have been found to influence alcohol drinking behavior or alcoholism substantially. This supports the original premise that the metabolic disposition of ethanol affects individuals' responses to it. The results suggest that any additional variants might also contribute to the spectrum of individual drinking preferences. Among heavy drinkers, the influence of the isozymes on risk of alcoholic liver disease has not been found to be great, suggesting that many other factors, perhaps interacting with the enzyme polymorphisms, are involved in determining susceptibility.