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Nutrient Interactions and Toxicity
Research Communication

Betaine Lowers Elevated S-Adenosylhomocysteine Levels in Hepatocytes from Ethanol-Fed Rats¹

Anthony J. Barak^*,,2, Harriet C. Beckenhauer^*, Mark E. Mailliard^*,, Kusum K. Kharbanda^*, and Dean J. Tuma^*,

^* VA Alcohol Research Center, Department of Veterans Affairs Medical Center, Omaha, NE 68105 and Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198

²To whom correspondence should be addressed. E-mail: ajbarak{at}yahoo.com.

Previous studies showed that chronic ethanol administration inhibits methionine synthase activity, resulting in impaired homocysteine remethylation to form methionine. This defect in homocysteine remethylation was shown to increase plasma homocysteine and to interfere with the production of hepatic S-adenosylmethionine (SAM) in ethanol-fed rats. These changes were shown to be reversed by the administration of betaine, an alternative methylating agent. This study was undertaken to determine additional effects of ethanol on methionine metabolism and their functional consequences. The influences of methionine loading and betaine supplementation were also evaluated. Adult Wistar rats were fed ethanol or a control Lieber-DeCarli liquid diet for 4 wk, and metabolites of the methionine cycle were measured in vitro in isolated hepatocytes under basal and methionine-supplemented conditions. S-Adenosylhomocysteine (SAH) concentrations were elevated in hepatocytes isolated from ethanol-fed rats compared with controls and in hepatocytes from both groups when supplemented with methionine. The addition of betaine to the methionine-supplemented incubation media reduced the elevated SAH levels. The decrease in the intracellular SAH:SAM ratio due to ethanol consumption inhibited the activity of the liver-specific SAM-dependent methyltransferase, phosphatidylethanolamine methyltransferase. Our data indicate that betaine, by remethylating homocysteine and removing SAH, overcomes the detrimental effects of ethanol consumption on methionine metabolism and may be effective in correcting methylation defects and treating liver diseases.

KEY WORDS: • hepatocytes • ethanol • S-adenosylhomocysteine • betaine • phosphatidylethanolamine methyltransferase

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