DL-methionine

Overview

DL-methionine is the racemic mixture of the two enantiomers of methionine — an essential sulfur-containing amino acid that cannot be synthesized de novo in mammals and must be obtained through dietary intake. Chemically designated as 2-amino-4-(methylthio)butanoic acid (Wikidata: Q180341), it serves as a critical precursor in one-carbon metabolism, supplying methyl groups via S-adenosylmethionine (SAM) for a broad array of methylation reactions targeting DNA, RNA, proteins, and lipids. The racemic DL-form is widely used in animal nutrition and dietary supplementation because both enantiomers can be metabolically converted to the biologically active L-form in vivo. Beyond its nutritional role, methionine occupies a pivotal position in the methylation cycle alongside related Metabolites such as DL-homocysteine, and its dysregulation has been implicated in neurodegenerative conditions, epigenetic reprogramming, and cancer cell metabolism.

The biological significance of methionine extends well beyond protein synthesis. As the universal methyl donor precursor, methionine feeds the SAM cycle, influencing gene expression through histone and DNA methylation. Tumor cells exhibit markedly elevated methionine dependency relative to normal tissues — a metabolic vulnerability increasingly exploited in cancer therapy. Simultaneously, methionine's role in modulating epigenetic regulators, activating oncogenic transcriptional co-activators such as Yes-associated protein (YAP), and sustaining amino acid transporter flux (notably through SLC6A15/B0AT2) positions it as a multifunctional mediator at the interface of nutrition, epigenetics, and disease.

Focus of Latest Publications

Recent publications have examined DL-methionine primarily as a dietary methyl-donor and amino acid supplement in animal nutrition, and as part of broader methionine-related metabolic and analytical contexts. In broiler chickens, DL-methionine supplementation was tested alongside betaine and turmeric extract, with the methionine-supplemented group showing improved final body weight, body weight gain, and feed conversion ratio, as well as higher serum total protein, albumin, and globulin. The study also reported coordinated changes in myogenic and intestinal parameters, supporting a role for DL-methionine in enhancing growth efficiency and protein metabolism.

Other studies focused on methionine dependence in cancer biology rather than supplementation per se. In oral squamous cell carcinoma, methionine deprivation markedly suppressed cell proliferation and migration in cultured cells, and dietary methionine restriction inhibited tumor growth in a xenograft model but caused systemic toxicity. To address this limitation, an attenuated Salmonella typhimurium strain engineered to overexpress L-methioninase was used to reduce methionine levels within tumor tissue, producing stronger anti-tumor activity in an orthotopic model and in patient-derived organoids with a favorable safety profile. In a separate lung cancer bone metastasis model, a low-methionine diet was combined with reduced-dose cisplatinum and evaluated for therapeutic synergy, reflecting continued interest in methionine restriction as an adjunct to chemotherapy.

Additional publications linked methionine to disease-associated metabolic and molecular processes. In Alzheimer's disease, methionine, homocysteine, and methylation levels were investigated as predictors of cognitive decline, highlighting the relevance of methionine-related metabolism to neurodegeneration. In glioma, MET-associated immune signatures were used to stratify prognosis and infer treatment response, with the broader MET pathway connected to immune evasion and resistance phenotypes. Methionine also appeared in mechanistic and methodological studies, including work on SLC6A15-mediated transport of neutral Amino Acids such as methionine, and a mass spectrometry method designed to eliminate artificial methionine oxidation during monoclonal antibody analysis.

A separate biochemical study showed that methionine residues can drive covalent chelation of zinc ions in linusorb peptides, with oxidation of methionine reducing zinc-binding capacity. Together, these publications portray DL-methionine and methionine-related pathways as relevant to nutrition, cancer metabolism, neurodegenerative biomarkers, transporter biology, and protein chemistry, with most therapeutic interest centered on methionine supplementation or restriction rather than direct pharmacologic targeting of DL-methionine itself.

Key Publications

NEWJul MET-associated immune prognostic signature predicts survival and guides personalized therapy in glioma. (Acta neuropathologica communications, 2026, PMID 42387647): "MET alterations promote tumor progression and immune evasion, yet their clinical implications in glioma immunotherapy remain unclear."
NEWJul MET Dependence Oversteps EGFR Dependence via Balancing Dimerization of the Receptor Tyrosine Kinases in Osimertinib-Resistant MET-Amplified, EGFR-Mutated Non-Small Cell Lung Cancer. (Thoracic cancer, 2026, PMID 42381268): "MET amplification is a common resistance mechanism to EGFR-TKIs; however, its effects on receptor dimerization and the resulting dependence on EGFR or MET signaling have not been fully elucidated."
NEWJan Synergy of a Low-methionine Diet and Reduced-dose Cisplatinum Eradicates Experimental Lung-cancer Bone Metastases in a Nude-mouse Model. (In vivo (Athens, Greece), 2026, PMID 42379791): "Methionine addiction is a fundamental hallmark of cancer, known as the Hoffman effect, and is targeted by methionine restriction (MR)."
Jun Effects of dietary methionine, betaine, and turmeric extract on growth performance, myogenic gene expression, serum protein profile, and intestinal histomorphology in broiler chickens. (Tropical animal health and production, 2026, PMID 42223732): "This study investigated the integrated physiological, molecular, and intestinal responses of broiler chickens to dietary supplementation with DL-methionine, betaine, and turmeric extract."
Jun Methionine, Homocysteine, and Methylation Levels Predict Cognitive Decline in Alzheimer's Disease. (CNS neuroscience & therapeutics, 2026, PMID 42201257): "...involves metabolic factors such as homocysteine, methionine, and DNA methylation in its pathogenesis."
May Unlocking SLC6A15 (B0AT2): A Dual-Platform Approach To Accelerate Drug Discovery for Neuropsychiatric Disorders. (Analytical chemistry, 2026, PMID 42118683): "SLC6A15 is a transmembrane protein that facilitates the symport of neutral and branched-chain amino acids, particularly proline, leucine, isoleucine, valine, and methionine, with sodium ions."
Jun Eliminating liquid chromatography-induced methionine oxidation of monoclonal antibodies using high-concentration TCEP injections: The "anTCEPtic" column cleaning method. (Journal of pharmaceutical sciences, 2026, PMID 42034288): "Artificial oxidation of methionine residues during LC/MS analysis of peptide mapping samples is a common issue arising from multiple possible contamination sources."
May Methionine-driven covalent chelation of Zn2+ by linusorb: a paradigm in hydrophobic cyclic peptide metal binding. (Food chemistry, 2026, PMID 41863922): "This study elucidates the covalent coordination mechanism underlying Zn2+ chelation by linusorbs (LOs) with different redox stages, highlighting the critical role of methionine (Met) residue."
May Genetically engineered Salmonella, SGN1, as a tumor microenvironment-targeting modality capable of methionine reduction for oral squamous cell carcinoma. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41786042): "...methionine deprivation drastically suppressed cell proliferation and migration."