The ARG47HIS variant has been designated as R48H based on numbering which includes the translation initiation codon (Edenberg, 2007). The HIS variant is associated with more rapid ethanol oxidation to acetaldehyde compared to the ARG variant.
The arg48 and his48 variants of ADH1B are often referred to as ADH1B*1 and ADH1B*2, respectively. However, Osier et al. (2002) noted that ADH1B*1 and ADH1B*2 are alleles that also include the ADH1B R370C variant (103720.0002).
Jornvall et al. (1984) determined that the 'atypical' variant of ADH1B, commonly found in persons of Asian origin, results from an arg48-to-his (R48H) substitution in exon 3 of the gene, in a position that binds the pyrophosphate group of coenzyme NAD(H); this change explains the functional differences between the 2 isozymes, including both a lower pH optimum and higher turnover of the atypical variant.
Matsuo et al. (1989) also showed that the 'typical' and 'atypical' forms of ADH1B differ by only a single amino acid: R48H, resulting from a G-to-A transition. The ADH1B*1 typical allele has an arg48 (CGC), whereas the ADH1B*2 atypical allele has his48 (CAC). The kinetic properties of the 2 variants in the coenzyme binding site were found to differ considerably: the V(max) of ethanol oxidation to acetaldehyde was increased by 100-fold in homozygotes for the his48 allele compared to homozygotes for the arg48 allele.
Using site-directed mutagenesis, Hurley et al. (1990) studied the effects of substitution of lysine, histidine, glutamine, and glycine for arginine-48 in beta-1/beta-1. They expressed the enzymes in E. coli and compared their kinetics.
