The Role of Liver Cytosolic Aldehyde Dehydrogenase in Ethanol Metabolism in DBA and C57Bl Mice
Cytosolic aldehyde dehydrogenase (A1DH) activity was increased in DBA and C57B1 mice following phenobarbital (Pb) treatment. The kinetic constants for the control and induced enzymes were similar in both inbred strains. The DBA mice showed enhanced rates of ethanol and acetaldehyde metabolism after Pb treatment, whereas the C57B1 mice did not. It was concluded that the cytosolic enzyme is more important for acetaldehyde metabolism in the DBA than in the C57B1 mice.
The role of the cytoplasmic aldehyde dehydrogenase (A1DH) in acetaldehyde (AcH) elimination following ethanol administration is a matter of some controversy. In rats the majority of hepatic A1DH activity is localized in the mitochondria (Horton and Barrett, 1975), and a “low Km” A1DH is thought to be responsible for the majority of AcH oxidation in vivo (Parilla et al., 1974). Redmond and Cohen (1971) showed that A1DH activity could be increased in mouse liver by phenobarbital (Pb) administration. The increase in liver A1DH activity was shown to be limited to the cytoplasmic fraction by Deitrich (1971) who also reported that the induction of the enzyme activity was controlled by an autosomal co-cominant gene.
The importance of the Pb induced AlDH activity in the metabolism of AcH following ethanol administration was examined by Eriksson et al., (1975) in rats. They concluded that the Pb induced A1DH played a minor role in AcH elimination. Petersen et al., (1977), however, showed that rats which had previously been selected for their high responsiveness to Pb induction of A1DH (RR line) eliminated ethanol and AcH at greater rates after Pb treatment than did the unresponsive (rr) line. Thus, the genotype of the animal used in the study was shown to be an important experimental parameter.
In this paper we report that DBA and C57B1 mice respond differently to Pb with respect to A1DH induction and ethanol and AcH metabolism.
KeywordsAldehyde Dehydrogenase C57Bl Mouse Ethanol Metabolism Acetaldehyde Metabolism C57B1 Mouse
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