S-adenosyl-L-methionine (SAM) (SAM)

S-adenosyl-L-methionine (SAM) is a vital metabolic cofactor and the universal methyl donor in biological systems, synthesized from the amino acid methionine and ATP by the enzyme methionine adenosyltransferase (MAT) (UniProt P31153) [1, 2]. It is essential for the methylation of DNA, RNA, proteins, and lipids, thereby playing a central role in epigenetic regulation and cellular signaling (PubChem CID 34755) [3]. In cancer biology, SAM is a focal point of the methionine addiction observed in many tumors, where elevated SAM synthesis supports rapid proliferation and altered epigenetic landscapes [4]. Modern therapeutic strategies, particularly for cancers harboring MTAP deletions, involve the use of MAT2A inhibitors (e.g., IDE397) to drastically reduce SAM levels, inducing a state of synthetic lethality by impairing PRMT5-mediated methylation [5, 6]. Beyond oncology, SAM (as SAMe) is utilized as a dietary supplement for treating depression, osteoarthritis, and liver disorders (StatPearls NBK559081) [7].

Other names

SAMeAdoMetAdemetionineS-adenosylmethionineS-adenosyl-L-methionine

S-adenosyl-L-methionine serves as the primary methyl donor for various methyltransferases. In oncology, the SAM axis is targeted by inhibiting methionine adenosyltransferase 2A (MAT2A), which depletes intracellular SAM levels [5]. This depletion leads to the inhibition of protein arginine methyltransferase 5 (PRMT5) activity, which is particularly lethal in MTAP-deleted cancer cells due to the accumulation of methylthioadenosine (MTA) that already partially inhibits PRMT5, resulting in impaired RNA splicing and cell death [6].