Baboon alcohol dehydrogenase isozymes: purification and properties of liver class I ADH. Moderate alcohol consumption reduces liver class I and class II ADH activities.
The major baboon liver isozyme of alcohol dehydrogenase (ADH-2) has been purified to homogeneity by affinity chromatography, and characterized as a "typical" Class I mammalian ADH isozyme. In contrast to human liver, which possesses three genetic isozymes (alpha 2, beta 2, and gamma 2) and three hybrid isozymes (alpha beta, alpha gamma, and beta gamma) of Class I ADH, baboon liver exhibits activity of a single major Class I isozyme (beta 2). Kinetic analyses, using alcohol substrates of differing chain lengths, and inhibition with pyrazole, support this classification. Agarose-IEF analyses, substrate specificity studies and immunochemical titrations of the major kidney ADH (ADH-1) also support the occurrence of a second Class I isozyme. The baboon was used as a model to study alcohol-induced changes in liver ADH phenotype following moderate and moderately high alcohol consumption. Four male and four female prepubertal baboons were fed nutritionally adequate liquid diets over a 40-week period, including control diets (weeks 1-8, 17-24, 32-40), moderate (12.5 percent of calories) alcohol diet (weeks 9-16), and a moderately high (25 percent of calories) alcohol diet (weeks 25-32). Liver ADH isozyme patterns and Class I ADH activities from biopsy samples, taken every 4 weeks, were monitored during the feeding study. Decreases in both Class I and Class II ADH activities were indicated in most animals, which may reflect adaptive mechanisms in the liver to continuing alcohol metabolism. Moreover, reversible changes were observed, with trends toward a recovery of ADH isozyme activities following return to the control liquid diets. These studies also have particular significance for human biomedical research work on alcohol, since most of the "drinking" population in typical drinking communities are moderate consumers of alcohol. This work, using the baboon as an animal model, has clearly indicated that alcohol consumption at such moderate levels, brings with it adaptations in the level of ADH isozymes in liver, which may play a protective role.
Holmes
R S
RS
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78284.
Meyer
J
J
VandeBerg
J L
JL
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000428:Alcohol Drinking / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D010215:Papio; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity
D007527:Isoenzymes; D000426:Alcohol Dehydrogenase