Figure 3.

Regulation of HMTs and DNMTs by SAM availability via folate and one-carbon metabolism. Dietary contributors are denoted by green arrows. Active one-carbon groups are generated via amino acid- and vitamin-dependent reactions in the folate cycle. These one-carbon groups are then used by methionine synthase (MTR) to generate methionine from homocysteine. Methionine is then adenylated to form SAM via methionine adenosyltransferase (MAT). SAM is used as a methyl donor by both HMTs and DNMTs, producing SAH. SAH is then converted to homocysteine, which can be converted back to methionine via a reaction that uses carbons from choline and produces dimethylglycine (DMG). MTHFR, methylenetetrahydrofolate reductase; SHMT, serine hydroxymethyltransferase; THF, tetrahydrofolate.