L-Methionine (Met)

L-Methionine is an essential sulfur-containing amino acid that serves as a fundamental building block for protein synthesis and a precursor for S-adenosylmethionine (SAM), the universal methyl donor for DNA and protein methylation (PubChem CID 6137). In the gastrointestinal lumen, free methionine is derived from dietary protein and is the primary source for systemic methionine levels. Many malignant cells exhibit a metabolic defect known as methionine dependence or the Hoffman effect, where they are unable to proliferate when methionine is replaced by its precursor homocysteine, unlike normal cells (Hoffman, 1985, PubMed: 3906698). Targeting free methionine in the gastrointestinal lumen using oral methioninase (methionine gamma-lyase) aims to degrade the amino acid before absorption, effectively starving methionine-dependent tumors of this vital nutrient (Tan et al., 1996, PubMed: 8920728). This therapeutic approach is being investigated as a non-toxic adjunct to chemotherapy and as a means to modulate metabolic health and longevity (Cell Cycle, 2014, PubMed: 24695150). By lowering the availability of methionine in the gut, clinicians can achieve systemic depletion without the severe restrictions of a methionine-free diet, which is often difficult for patients to maintain.

Other names

L-MethionineMet(S)-2-Amino-4-(methylmercapto)butyric acidDietary methionineFree methionine

Enzymatic depletion of the methionine pool in the gastrointestinal tract to lower systemic levels and exploit the methionine dependence of cancer cells.