The effect of chronic ethanol ingestion on ethanol metabolizing enzymes in isolated periportal and perivenous rat hepatocytes.
Periportal (pp) and perivenous (pv) hepatocyte populations were separated using a two-directional closed perfusion technique with selective addition of collagenase either to direct or retrograde perfusions (Väänänen, H. et al., Liver 1983; 3:131). The activity of GPT in hepatocytes from the pp-area was 1.9 times higher than in cells from the pv-area (p less than 0.01). The distribution of glutamate dehydrogenase and pyruvate kinase activities was reversed; pp/pv ratios of 0.7 and 0.5, respectively, were observed (p less than 0.001, p less than 0.05). Chronic ethanol consumption for 12 weeks (mean daily ethanol intake 11.4 gm per body weight corresponding to 29% of total energy intake) did not cause histological changes but decreased GPT activity, increased glutamate dehydrogenase and pyruvate kinase activities and did not alter their pp/pv distribution. Alcohol dehydrogenase and aldehyde dehydrogenase activities were evenly distributed in pp- and pv-hepatocytes. Chronic ethanol treatment slightly decreased alcohol dehydrogenase activity (p less than 0.05) and increased the activity of low Km aldehyde dehydrogenase (p less than 0.001, p less than 0.05). The specific activity of NADPH-dependent microsomal ethanol oxidation was 50% higher in pv-hepatocytes (p less than 0.05). Chronic ethanol treatment did not increase the specific activity of microsomal ethanol oxidation but reduced the pp-pv activity difference. The results indicate that the enzymatic capacity to oxidize ethanol is evenly distributed in the acinus and that, after long-term moderate ethanol treatment, despite lack of parenchymal lesions, changes in the activity of enzymes involved in ethanol metabolism are observed.(ABSTRACT TRUNCATED AT 250 WORDS)
D000410:Alanine Transaminase / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000437:Alcoholism / Q000201:enzymology* / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000444:Aldehyde Dehydrogenase; D005969:Glutamate Dehydrogenase; D000410:Alanine Transaminase; D011770:Pyruvate Kinase