Figure 3.

One-carbon metabolism, DNA/histone methylation, and drug interaction. Folate is the center of one-carbon metabolism, which involves three biochemical processes, the folate cycle, methionine cycle, and trans-sulfuration pathway. A set of enzymes (in bold) and coenzymes (in green boxes) catalyzes the different reactions. DNA methyltransferases (DNMTs) control DNA- and histone methylation through methyl groups from SAM. Deficits in folic acid and vitamins B12, B6, and B2 increase homocysteine levels inhibiting DNMTs. Dopamine replacement therapies supply L-dopamine that is converted by either catechol-O-methyltransferase (COMT) into 3-O-Methyldopa (3-OMD) by consuming methyl groups from S-adenosylmethionine (SAM), or aromatic L-amino acid decarboxylase (AADC) to generate dopamine. This dopamine can be metabolized into two substances, 3-ethoxyxtyramine (3-MT) and 3,4-Dihydroxyphenylacetic acid (DOPAC), both converted into homovanillic acid (HVA) and excreted in the urine. Both reactions are catalyzed by COMT using methyl groups from SAM, and by monoamine oxidase (MAO).