ADH is the primary enzyme that metabolizes alcohol. The human ADH gene family clusters on chromosome 4q21 in a region spanning ~370 kilobases (112, 113). Currently, seven human ADHs have been identified, of which six have been structurally and functionally characterized. However, the seventh (ADH6) has not been isolated as a protein in vivo, and its role in ethanol metabolism is still unknown (113) (Table 1). ADH accounts for about 3% of soluble protein in the liver. The Class I ADHs, ADH1A, ADH1B, and ADH1C, are responsible for most of the oxidation of ethanol in the liver and can form both homo- and heterodimeric forms of the three subunits, such as αα, αβ, ββ, βγ, γγ, among others. ADH4 is exclusively expressed in the liver, while ADH7 is the only ADH not expressed there (113). ADH5 is ubiquitously expressed in human tissues but has a low affinity for ethanol, so it does not significantly contribute to hepatic ethanol oxidation. As shown in Table 1, these isozymes have different kinetic properties, allowing for flexibility in the regulation of alcohol metabolism at different exposures.
