FIGURE 2.

Metabolism of SAM. SAM is synthesized from methionine and ATP by methionine adenosyltransferase (MAT). In methylation reactions, SAM is sequentially converted to S-adenosylhomocysteine (SAH), homocysteine (Hcy) and methionine with 5-methyl-tetrahydrofolate (THF) or with betaine as the methyl donor. Serine-glycine metabolism provides one-carbon unit to the folate cycle. Serine biosynthesis is controlled by LKB-AMPK-mTOR pathway. In the methionine salvage pathway, SAM is converted to 5′-methylthioadenosine (MTA), which is salvaged back for SAM generation. MTA inhibits the activity of PRMT5. MAT, methionine adenosyltransferase; MTA, 5′-methylthioadenosine; THF, tetrafolate; LKB1, liver kinase B1; mTOR, mammalian target of rapamycin complex; SAH, S-adenosylhomocysteine; Hcy, homocysteine; MTAP, MTA phosphorylase; DMG, dimethylglycine; PRMT5, arginine methyltransferase 5.