Effect of chronic ethanol or acetaldehyde on hepatic alcohol and aldehyde dehydrogenases, aminotransferases and glutamate dehydrogenase.
Ethanol or acetaldehyde orally administered (15% and 2% respectively in drinking water) to male Wistar rats for three months induced alterations in the main liver enzymes responsible for ethanol metabolism, aspartate and alanine aminotransferases and NAD glutamate dehydrogenase. Ethanol produced a significant decrease in the activity of soluble alcohol dehydrogenase, while acetaldehyde induced alterations both in soluble and mitochondrial aldehyde dehydrogenases: soluble activity was significantly higher than in the control and ethanol-treated groups, and mitochondrial activity was significantly diminished. Both soluble aspartate and alanine aminotransferases showed pronounced increases by the chronic effect of acetaldehyde, while mitochondrial activities were practically unchanged by the effect of ethanol or acetaldehyde. Mitochondrial NAD glutamate dehydrogenase showed a rise in its activity both by the effect of chronic ethanol and acetaldehyde consumption. The level of metabolites assayed in liver extracts showed marked differences between ethanol and acetaldehyde treatment which indicates that ethanol produced a remarkable increase in glutamate, aspartate and free ammonia together with marked decrease in pyruvate and 2-oxoglutarate concentrations. Acetaldehyde consumption induced a significant decrease in 2-oxoglutarate and pyruvate concentrations. These observations suggest that ethanol has an important effect on the urea cycle enzymes, while the effect of acetaldehyde contributes to the impairment of the citric acid cycle.
Cascales
C
C
Cascales
M
M
Santos-Ruiz
A
A
D000079:Acetaldehyde / Q000008:administration & dosage / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D000431:Ethanol; D018698:Glutamic Acid; D000641:Ammonia; D000429:Alcohol Oxidoreductases; D000444:Aldehyde Dehydrogenase; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000079:Acetaldehyde