Alcohol dehydrogenases, aldehyde dehydrogenases, and related enzymes

Abstract

Several new structures have recently been determined for dehydrogenases which are involved in alcohol metabolism. These structures give new insight into catalytic properties, structure-function relationships, and evolutionary connections. They also explain the structural basis for known metabolic deviations. Among alcohol dehydrogenases, the first primary structures for human enzyme forms have been reported (the beta 1, gamma 1, and "atypical" beta-chains). These structures explained functional properties and enzymatic differences, showed separate and parallel events of isozyme divergence, and suggested differential gene activations. Similarly, for aldehyde dehydrogenases, the first cytoplasmic isozyme structures have been reported in man and horse. The data showed positions of functionally important residues, and established clear differences between the mitochondrial and cytoplasmic isozymes of aldehyde dehydrogenase. For sorbitol dehydrogenase, the first complete structure which establishes a relationship with other "long" alcohol dehydrogenases in a scheme exhibiting both structural divergence and functional convergence has also been reported. Finally, glucose dehydrogenase has been structurally linked with sorbitol dehydrogenase, extending the scheme and adding further enzymes to the group of "short" alcohol dehydrogenases.