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Nutrient Interactions and Toxicity

A Comparison of the Effects of Betaine and S-Adenosylmethionine on Ethanol-Induced Changes in Methionine Metabolism and Steatosis in Rat Hepatocytes¹

Kusum K. Kharbanda^*,,2, David D. Rogers, II^*, Mark E. Mailliard^*,, Gerri L. Siford, Anthony J. Barak^*,, Harriet C. Beckenhauer^*, Michael F. Sorrell^*, 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: kkharbanda{at}unmc.edu.

Previous studies showed that chronic ethanol administration alters methionine metabolism in the liver, resulting in increased intracellular S-adenosylhomocysteine (SAH) levels and increased homocysteine release into the plasma. We showed further that these changes appear to be reversed by betaine administration. This study compared the effects of betaine and S-adenosylmethionine (SAM), another methylating agent, on ethanol-induced changes of methionine metabolism and hepatic steatosis. Wistar rats were fed ethanol or control Lieber-Decarli liquid diet for 4 wk and metabolites of the methionine cycle were measured in isolated hepatocytes. Hepatocytes from ethanol-fed rats had a 50% lower intracellular SAM:SAH ratio and almost 2-fold greater homocysteine release into the media compared with controls. Supplementation of betaine or SAM in the incubation media increased this ratio in hepatocytes from both control and ethanol-fed rats and attenuated the ethanol-induced increased hepatocellular triglyceride levels by 20%. On the other hand, only betaine prevented the increase in generation of homocysteine in the incubation media under basal and methionine-loaded conditions. SAM can correct only the ratio and the methylation defects and may in fact be detrimental after prolonged use because of its propensity to increase homocysteine release. Both SAM and betaine are effective in increasing the SAM:SAH ratio in hepatocytes and in attenuating hepatic steatosis; however, only betaine can effectively methylate homocysteine and prevent increased homocysteine release by the liver.

KEY WORDS: • hepatocytes • ethanol • S-adenosylhomocysteine • S-adenosylmethionine • betaine

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