cDNA structures of class I human liver alcohol dehydrogenases.

We have determined cDNA structures coding for class I subunits of human liver alcohol dehydrogenase. Two clones have been identified which contain the cDNA sequence coding for the alpha subunit. One of the clones had a 139-nucleotide internal deletion of interest in relation to intron/exon splice junctions, domain borders and evolutionary connections with other dehydrogenases. Different size classes of cDNA clones coding for the beta subunit were characterized with 3' non-coding regions of 213, 590 and 1331 nucleotides. In addition, two unused polyadenylation signals were found, indicating that signals other than AATAAA, are required for 3' end formation. Determination of cDNA structures corresponding to the gamma 1 and gamma 2 subunits makes it possible to explain the kinetic differences between the two allelic subunits in terms of two amino acid replacements. In total, 35 of 374 amino acid residues differ between the class I subunits. Only in the beta pleated sheet region of the coenzyme-binding domain is an almost complete lack of substitutions noted, illustrating the importance of this region. The class II, with pi subunits, has also been determined and shows a much lower extent of homology.