Structurally, the ADH1B protein presents three binding sites: two metal-binding sites for the catalytic zinc and the structural zinc, respectively; and a nucleotide biding site for the NAD (Nicotinamide Adenine Dinucleotide) coenzyme. Most studies of ADH1B enzymatic activities mainly focused on three alleles (which used to be designated ADH1B*1, ADH1B*2, and ADH1B*3) based on two missense substitutions (Arg48His, rs1229984; Arg370Cys, rs2066702 – the “*1” variant has neither of these two possible substitutions) commonly present in various human populations (Table 1). ADH1B*2 (Arg48His, rs1229984) occurs mostly in Asian and European-ancestry populations, while ADH1B*3 (Arg370His, rs2066702) is seen almost exclusive in African-ancestry populations. Both protein products of ADH1B rs1229984 and rs2066702 facilitate the release of the NAD coenzyme at the end of the reaction with a consequent 70- to 80-fold higher turnover rate than the protein product of ADH1B reference sequences [Edenberg 2007; Hurley and others 2003]. That is, the minor alleles are in both cases more active than the common alleles.
