STRUCTURAL FEATURES OF STOMACH ALDEHYDE DEHYDROGENASE DISTINGUISH DIMERIC ALDEHYDE DEHYDROGENASE AS A VARIABLE ENZYME - VARIABLE AND CONSTANT ENZYMES WITHIN THE ALCOHOL AND ALDEHYDE DEHYDROGENASE FAMILIES

Stomach aldehyde dehydrogenase was structurally evaluated by analysis of peptide fragments of the human enzyme and comparisons with corresponding parts from other characterized aldehyde dehydrogenases. The results establish a large part of the structure, confirming that the stomach enzyme is identical to the inducible or tumor-derived dimeric aldehyde dehydrogenase. In addition, species variations between identical sets of different aldehyde and alcohol dehydrogenases reveal that stomach aldehyde dehydrogenase exhibits a fairly rapid rate of evolutionary changes, similar to that for the likewise 'variable' classical alcohol dehydrogenase, sorbitol dehydrogenase, and cytosolic aldehyde dehydrogenase but in contrast to the 'constant' class III alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase. This establishes that rates of divergence in the aldehyde and alcohol dehydrogenases are unrelated to subunit size or quaternary structure, highlights the unique nature of class III alcohol dehydrogenase, and positions the stomach aldehyde dehydrogenase in a group with more ordinary features.