Humans have seven ADHs that can carry out the first step in alcohol metabolism. The genes encoding these enzymes all are localized on chromosome 4 in a head-to-tail array about 370 kb long. The enzymes produced from these genes all differ slightly in their activities (see table 1): The ADH1A, ADH1B, and ADH1C genes1 produce closely related proteins that function as homo- and heterodimers (Hurley et al. 2002); their kinetic properties, tissue localization, and developmental expression all support major roles in oxidative ethanol metabolism in the liver.The ADH4 gene is expressed almost exclusively in the liver (Hurley et al. 2002), where it contributes significantly to ethanol oxidation at higher levels of consumption.The product of the ubiquitously expressed ADH5 gene is the glutathione-dependent formaldehyde dehydrogenase (also known as nitrosoglutathione reductase [GSNOR]). The physiological substrates for ADH5 (α-ADH) are compounds (i.e., adducts) formed during the reaction between glutathione and formaldehyde and between glutathione and nitric oxide (Que et al. 2005; Sanghani et al. 2000). The main functions of this enzyme are to oxidize formaldehyde to formic acid and to terminate nitric oxide
