Prenatal and Postnatal Epigenetic Programming: Implications for GI, Immune, and Neuronal Function in Autism

Figure 2

Redox and methylation pathways in neurons. The amino acid cysteine is rate-limiting for glutathione (GSH) synthesis and it is provided either by uptake from astrocyte-derived cysteine or by transsulfuration of homocysteine (HCY). The methionine cycle of methylation (lower right) depends upon both dietary methionine (MET) and remethylation of HCY by methionine synthase. Since formation of HCY from S-adenosylhomocysteine (SAH) is reversible and SAH inhibits methylation, decreased methionine synthase activity (e.g., caused by oxidative stress) both augments GSH synthesis and inhibits methylation reactions. Thus, redox status and methylation activity are closely linked. The D4 dopamine receptor carries out a cycle of dopamine-stimulated phospholipid methylation which is completely dependent upon methionine synthase and is therefore also sensitive to oxidative stress. Growth factors promote EAAT3 activity by increasing its location on the cell surface. EAAT3 activity is inhibited by oxidative stress and by food-derived opiate peptides.