Alcohol has multiple effects on methyl donors (Mason and Choi, 2005) and appears to interfere with the folate-methyl metabolic pathway for methyl donors by inhibiting methionine synthase and methionine adenosyltransferase. Inhibition of methionine synthase also creates a “methylfolate trap,” analogous to what occurs in vitamin B12 deficiency (Cravo and Camilo, 2000; Mason and Choi, 2005). Alcohol ingestion in animals has been shown to inhibit folate-mediated methionine synthesis, thereby interrupting critical methylation processes mediated through s-adenosyl methionine, the activated form of methionine and substrate for biologic methylation. In addition, some evidence indicates that alcohol may redirect the utilization of folate toward serine synthesis and thereby interfere with a critical function of methylene tetrahydrofolate and thymidine synthesis (LaBaume et al., 1987; Cravo and Camilo, 2000). Thus, alcohol exposure, by resulting in downstream epigenetic modifications, could bridge the gene-environment interaction, providing a new causal paradigm for the neurodevelopmental deficit.
