The influence of ethanol on hepatic transmethylation

One of the most important biochemical pathways in the organism is the biosynthesis of methionine from the methylation of homocysteine. Two different reactions are responsible for this methylation, one utilizing N5-methyltetra-hydrofolate as a methylating agent and the other using betaine as the methyl donor. This paper reviews some recent findings in this laboratory, which demonstrate that ethanol-feeding to rats impairs the folate-induced reaction. Our findings also show that this impairment is compensated for through the adaptive increase in the enzyme using betaine in the biosynthesis of methionine. Further studies indicate that the mechanism of action in the impairment may occur through the formation of individual adducts between the folate-induced enzyme (methionine synthetase), its essential cofactors and acetaldehyde, a metabolic product of ethanol. These findings suggest a basis for why rats are more resistant to alcoholic liver injury than humans and may offer a means of protecting against alcoholic liver injury in man.