ABSTRACT
Several mechanisms have been described by which chronic alcohol consumption may interact with one-carbon metabolism and thereby disturb methylation reactions. Interactions may occur with absorption, storage, biologic transformation, and excretion of compounds which are closely involved with methyl group transfer. Among the factors that may be affected are folate, vitamin B6, and lipotropes, such as choline, betaine, and methionine. In particular, the production of S-adenosyl-L-methionine (SAMe), the
universal methyl group donor in methylation reactions, is impaired due to various mechanisms, including the formation of methyl groups, their transport by tetrahydrofolate, and finally their transfer to methionine, the precursors of SAMe. Alcohol interacts with SAMe synthesis through the inhibition of crucial metabolic enzymes such as methionine synthase and methionine adenosyltransferase either by producing oxidative stress or by direct inhibition of vitamin B6, a coenzyme in various transmethylation reactions. Thus, alcohol inhibits the production of glutathione by inhibiting cystathionine-β-synthase, a reaction in which glutathione is formed via the intermediates cystathionine and cysteine. Due to the inhibition of SAMe production, the integrity of cellular membranes may be compromised by inhibiting methylation of membrane phospholipids.
