SAM (S-adenosylmethionine)

S-adenosylmethionine (SAM) is the principal biological methyl-group donor, formed by the condensation of methionine with adenosine triphosphate (ATP) in a reaction catalysed by methionine adenosyltransferase. After donating its methyl group to substrates ranging from DNA and histones to neurotransmitters and phospholipids, SAM is converted to S-adenosylhomocysteine (SAH), which is then hydrolysed to homocysteine — a branch point between remethylation back to methionine and the transsulfuration pathway toward cysteine and glutathione. Intracellular SAM:SAH ratio serves as a cellular indicator of methylation capacity; declining SAM availability with age or methionine restriction is proposed to alter epigenetic programming and modulate longevity in several model organisms, though the net effects in mammals remain context-dependent.