Sorbitol dehydrogenase: cDNA coding for the rat enzyme. Variations within the alcohol dehydrogenase family independent of quaternary structure and metal content.

Two separate cDNA-clones, together coding for rat sorbitol dehydrogenase, have been isolated from a liver cDNA library in lambda gt11 by screening with oligonucleotide probes. One clone contained a 1020-bp fragment starting at the codon for amino acid residue 104 and ending with a 261-bp 3' non-coding region, the second encompassed the entire 5' region and ended with a 3' truncation corresponding to amino acid residue 315. The coding region consists of 356 amino acid residues, one more than in the human and sheep enzymes. The presence of the extra residue at position 3, a proline, can be explained by a shifted splice point in the mRNA. The primary structure of rat sorbitol dehydrogenase allows triplet comparisons of three distinct rat-ungulate-human enzymes differing in quaternary structure and metal content within the zinc-containing alcohol dehydrogenase family. The variability of sorbitol dehydrogenase (tetramer with one zinc atom/subunit; no activity towards ethanol) is large (18%), exactly like that for the class I alcohol dehydrogenase (dimer with two zinc atoms/subunit; no activity towards sorbitol), differing threefold from that of the class III alcohol dehydrogenase/glutathione-dependent formaldehyde dehydrogenase (dimer with two zinc atoms/subunit; 6% variability) suggesting that the distinct extents of variability within this protein family are independent of substrate specificity, metal content and quaternary structure.