Humans have seven different genes, called ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, and ADH7, that encode medium-chain ADHs (see Table 1).2 These genes all are aligned along a small region of chromosome 4 (Figure 1). The ADH enzymes they encode function as dimers—that is, the active forms are composed of two subunits. Based on similarities in their amino acid sequences and kinetic properties (e.g., the rate at which ethanol is oxidized), the seven ADH types have been divided into five classes (see Table 1). The three class I genes, ADH1A, ADH1B, and ADH1C, are very closely related; they encode the α, β, and γ subunits, which can form homodimers or heterodimers3 that account for most of the ethanol-oxidizing capacity in the liver (Hurley et al. 2002; Lee et al. 2006). ADH4 encodes π-ADH, which contributes significantly to ethanol oxidation at higher concentrations (Table 2). ADH5 encodes χ-ADH, a ubiquitously expressed formaldehyde dehydrogenase with very low affinity for ethanol. ADH6 mRNA is present in fetal and adult liver, but the enzyme has not been isolated from tissue and little is known about it. ADH7 encodes σ-ADH, which contributes to both ethanol and retinol oxidation.
