Sadenosylmethionine

S-adenosyl-L-methionine (SAM), also known as SAMe or AdoMet, is a natural sulfonium compound formed from methionine and ATP by the enzyme methionine adenosyltransferase. It functions as a universal methyl donor in a broad range of transmethylation reactions, transferring methyl groups to substrates such as DNA, RNA, proteins, lipids, and neurotransmitters, and generating S-adenosylhomocysteine (SAH) in the process. SAH is subsequently hydrolyzed to homocysteine and adenosine, linking SAM metabolism to the methionine cycle.

Synthesis and regulation of SAM occur in most tissues, with MAT1A (liver) and MAT2A (extrahepatic tissues) controlling tissue-specific production. The cellular abundance of SAM and the ratio of SAM to SAH, often referred to as methylation potential, regulate methyltransferase activity. Homocysteine, produced from SAH, can be remethylated back to methionine via methionine synthase (which uses folate-derived methyl groups and vitamin B12) or betaine-homocysteine methyltransferase, integrating SAM metabolism with folate and B12 status and the broader one-carbon metabolism network.

In addition to methylation, SAM serves as a precursor for polyamine synthesis through decarboxylated SAM and participates in the biosynthesis of several essential metabolites, including phosphatidylcholine. Because of its central role in methylation reactions, SAM levels and the SAM/SAH ratio are sensitive to nutritional status, particularly folate and B12, and can influence epigenetic and metabolic processes.

SAM is also available as a dietary supplement and has been studied for conditions such as major depressive disorder, osteoarthritis, and liver disease. Evidence for efficacy varies by condition. Adverse effects are typically mild (e.g., gastrointestinal symptoms, headaches), though mania may occur in susceptible individuals, and interactions with other psychotropic drugs can occur.