Figure 5.

DNA methylation in one-carbon metabolism centered around the folate (left) and methionine (right) cycles. Folate is reduced to dihydrofolate (DHF) and tetrahydrofolate (THF). THF is changed into 5,10-methylene THF with the possible involvement of vitamin B6; 5,10-methylene THF is converted to 5mTHF, which is demethylated to complete the folate cycle. Vitamin B2 can also be involved in these steps. Carbon from the 5mTHF demethylation enters the methionine cycle through the methylation of homocysteine to produce methionine by methionine synthase with vitamin B12 as a cofactor. Methionine may generate S-adenosyl-methionine (SAM), which provides methyl groups for DNA methyltransferases (DNMTs) that methylate DNA. SAM is then demethylated to S-adenosylhomocysteine (SAH), which is converted back to homocysteine.