Figure 3.

The intersection between metabolic cycles and DNA methylation cycle. (a) DNMT and methionine cycle. To methylate cytosine, DNMT uses S‐adenosyl methionine (SAM) as the methyl group donor, producing S‐adenosylhomocysteine (SAH) as a result. SAH is then recycled back to the methionine cycle (Fig. 1), regenerating SAM for additional methylation. (b) TET and Krebs cycle. With reduced iron (Fe²⁺) as a co‐factor, TET converts the substrates 5mC, α‐ketoglutarate (αKG), and oxygen into the products 5hmC, succinate, and carbon dioxide. TET can further oxidize 5hmC into 5fC and 5caC (not depicted). Succinate can be shuttled back to the Krebs cycle and regenerating αKG. Additional αKG can be derived from glutamine via glutaminolysis (Fig. 1).