Aldehyde Dehydrogenase and Ethanol Preference in Mice

Abstract

Abstract The aldehyde dehydrogenases from livers of the inbred mouse strains C57BL/6J, DBA/2J, and the F1 generation of the cross between these strains (C57BL/6J x DBA/2J) have been purified over 60-fold. Alcohol dehydrogenase activity is not present in the purified enzyme preparation. Enzyme preparations from both strains and from the F1 cross specifically require NAD but can oxidize a variety of aldehyde substrates. Results obtained previously, using a crude liver homogenate as enzyme source and indoleacetaldehyde as substrate, demonstrate a 2- to 3-fold greater aldehyde-oxidizing capacity in the liver extracts of the C57BL/6J strain compared to similar extracts from the DBA/2J mice. Mice of the former strain prefer a 10% solution of alcohol to water, whereas DBA/2J mice avoid alcohol in this preference test. F1 generation mice are intermediate to the parents with regard to alcohol preference and aldehyde-oxidizing capacity. The purified enzymes from the two inbred sources are indistinguishable as determined by disc gel electrophoresis, ion exchange chromatography, and gel filtration criteria. Nevertheless, the aldehyde dehydrogenases of C57BL/6J and DBA/2J mice exhibit 2- to 3-fold differences in the Michaelis constants of aldehyde substrates. Reaction velocity differences between the two enzyme preparations are particularly apparent when acetaldehyde is the substrate. The C57BL/6J aldehyde dehydrogenase is activated by 10-6 m acetaldehyde to a reaction velocity greater than 2 times its original value, whereas the DBA/2J aldehyde dehydrogenase exhibits substrate activation only above 10-3 m acetaldehyde. Finally, it has been demonstrated by chromatographic analysis that, following intraperitoneal ethanol injection, acetaldehyde accumulates in the blood of DBA/2J mice to a greater extent than it does in C57BL/6J mice. This observation lends support to the possibility that the lower aldehyde dehydrogenase activity of the DBA/2J mice results in an acetaldehyde-induced avoidance of ethanol.