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Effect of ethanol on homocysteine/methionine metabolism and DNA methylation

Methionine, which is formed by methylation of homocysteine (using either 5-methyl tetrahydrofolate (5-methyl THF) or betaine as a methyl donor), is essential for the production of s-adenosyl-methionine (SAM), which in turn is used to methylate DNA. Chronic heavy drinking reduces folate levels and inhibits methionine synthase (MS), resulting in a reduction of methionine and SAM and the concurrent increase in homocysteine and s-adenosyl-homocysteine (SAH). SAH further inhibits DNA methyltransferases (DNMTs), ultimately resulting in global hypomethylation of DNA. (Source: Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res 2013;35(1):6-16. Public domain.)

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