Structural relationships among aldehyde dehydrogenases.

Abstract

Two functional regions of liver aldehyde dehydrogenase were characterized before; other structures of homologous parts from isoenzymes have now been determined to obtain further information on the isoenzyme relationships. In a 22-residue region from the horse cytoplasmic and mitochondrial isoenzymes, substitutions occur at 12 positions, including a continuous six-residue portion characterized by non-conservative changes. In contrast, the same structure from the cytoplasmic isoenzyme shows exchanges at only three positions when compared to its counterpart from human cytoplasm. A similar estimate of substitution frequency between species is obtained from a larger sampling at 236 positions. Thus, the isoenzyme difference between aldehyde dehydrogenases from the same species is about five-fold greater than the species difference between corresponding isoenzymes. Hence, the relationship between cytoplasmic and mitochondrial aldehyde dehydrogenases, while recognizable, is distant. This is compatible with the fact that a property such as high sensitivity to disulfiram is a characteristic of only the cytoplasmic isoenzyme.