Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases

Abstract

Usual human livers contain two major ALDH isozymes, i.e., cytosolic ALDH 1 and mitochondrial ALDH 2, while approximately 50% of Orientals are “atypical” and have only the ALDH 1 and are missing the ALDH 2. Instead, the atypical livers contain an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH 2 component. Some Orientals are found to be atypical also in the ALDH 1 locus, i.e., they are missing the enzymatically active ALDH 1 but contain a large amount of CRM corresponding to the ALDH 1 component. cDNA for ALDH 1 and that for ALDH 2 were cloned and their nucleotide sequences were determined. The amino acid sequences of ALDH 1 and ALDH 2 were deduced from their cDNA sequences. The molecular abnormality of the inactive ALDH 2 2 is found to be the substitution of Glu at the 14th position from the COOH-terminal of the protein by Lys which resulted from G → A transition in the gene.