Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine.
Phosphatidylethanolamine N-methyltransferase participates in the synthesis of membrane phosphatidylcholine. Its activity was reported to be decreased in patients with alcoholic cirrhosis, but it is not known whether this is a consequence of the cirrhosis or precedes it. This question was studied in a baboon model of alcohol-induced fibrosis. Phosphatidylethanolamine N-methyltransferase activity was measured in sequential percutaneous needle liver biopsies by the conversion of phosphatidylethanolamine to phosphatidylcholine, using radioactive S-adenosylmethionine as a methyl donor. Chronic alcohol consumption (1-6 years) significantly decreased hepatic phospholipid and phosphatidylcholine levels and reduced phosphatidyl-ethanolamine N-methyltransferase activity even before the development of fibrosis. These effects were prevented or attenuated by supplementing the diet with 2.8 g/1000 kcal of a preparation rich in dilinoleoyl phosphatidylcholine, a highly bioavailable phosphatidylcholine species. There were significant (p < 0.001) correlations between phosphatidylethanolamine N-methyltransferase activity and both hepatic phosphatidylcholine (r = 0.678) and total phospholipid (r = 0.662).


CONCLUSIONS
1. Alcohol consumption diminishes phosphatidylethanolamine N-methyltransferase activity prior to the development of cirrhosis and decreases the hepatic content of its product, namely phosphatidylcholine, a key component of cell membranes. This may promote hepatic injury and possibly trigger fibrosis. 2. Phosphatidylcholine administration ameliorates the ethanol-induced decrease in phosphatidylethanolamine N-methyltransferase activity and corrects phospholipid and phosphatidylcholine depletions, thereby possibly contributing to the protection against alcoholic liver injury.
Lieber
C S
CS
Section of Liver Disease and Nutrition, Veterans Administration Medical Center, Bronx, NY 10468.
Robins
S J
SJ
Leo
M A
MA
D000818:Animals; D001706:Biopsy; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010215:Papio; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D050918:Phosphatidylethanolamine N-Methyltransferase; D010743:Phospholipids / Q000378:metabolism
D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D000431:Ethanol; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase