Formation of the 37KD protein-acetaldehyde adduct in liver during alcohol treatment is dependent on alcohol dehydrogenase activity.
Protein-acetaldehyde adducts (protein-AAs) are formed in vivo during chronic alcohol ingestion. These protein-AAs reported thus far include a 37KD protein-AA in liver cytosol, cytP450IIE 1-AA in hepatic microsomes, hemoglobin-AA, and serum protein-AAs. It has been postulated that acetaldehyde or perhaps a reactive acetaldehyde radical generated by the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) explains the formation of the cytP450IIE1-AA. The source of acetaldehyde responsible for the formation of the cytosolic 37KD protein-AA has not been determined. In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein-AA in vivo and in vitro. It was found that feeding rats with an alcohol-containing liquid diet supplemented with cyanamide enhanced while a diet supplemented with pyrazole completely abolished the formation of the 37KD liver protein-AA. The liver of rats fed the pyrazole supplemented alcohol-containing diet showed significantly higher content of cytP450IIE1 than that of rats fed the diet containing alcohol alone. On the other hand, feeding the cyanamide supplemented alcohol-containing liquid diet did not further enhance the content of cytP450IIE1. Similarly, adding cyanamide to the culture medium enhanced while adding 4-methylpyrazole inhibited the production of the 37KD protein-AA by cultured hepatocytes even though the combination of alcohol and 4-methylpyrazole increased the content of cytP450IIE1 2-fold over that in control cells. These results demonstrate that the formation of the 37KD liver Protein-AA is dependent on ADH and not on MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)
Lin
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RC
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Lumeng
L
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D000079:Acetaldehyde / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000502:physiology*; D000429:Alcohol Oxidoreductases / Q000502:physiology; D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008970:Molecular Weight; D011506:Proteins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D011720:Pyrazoles; D000431:Ethanol; C031280:pyrazole; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C092153:microsomal ethanol-oxidizing system; D000426:Alcohol Dehydrogenase; C019642:alcohol dehydrogenase (NADP+); D000079:Acetaldehyde