The AtlasAmino acidsNonpolar, aliphatic
MethionineMet · M
Every protein you make starts with it, and every methyl group you hand out passes through it first.
Molecule · Met · 9 heavy atoms
Methionine
C5H11NO2S149.22 g/mol
Every protein you make starts with it, and every methyl group you hand out passes through it first.
Built fromthe charted ones open their own entry
- Codes
- Met · M
- Formula
- C5H11NO2S
- Molar mass
- 149.22 g/mol
- Systematic name
- (2S)-2-amino-4-(methylsulfanyl)butanoic acid
- Side chain
- 2-(Methylthio)ethyl: two carbons then a sulfur carrying a methyl group; nonpolar.
- Class
- Nonpolar, aliphatic
- In the diet
- Essential
- Carbon skeleton
- Glucogenic
- pKa
- α-COOH 2.28 · α-NH3+ 9.21
- Isoelectric point
- pH 5.74
- Hydropathy
- +1.9 (Kyte–Doolittle)
- Codons
AUG
pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.
In brief
What it is
A sulfur-containing essential amino acid whose side chain ends in a methyl group on a sulfur atom: a thioether, unreactive enough to sit inside proteins and reactive enough to be the body’s methyl donor once it is activated 1.
Why it matters
Methionine is the first amino acid of nearly every protein, because its codon, AUG, is the start signal. Activated as S-adenosylmethionine it supplies the methyl groups for DNA, histones, neurotransmitters and hundreds of other molecules, and what is left over becomes homocysteine 2,3.
Where it runs short
Diets low in methionine are mostly plant diets: plant protein carries about 1% methionine against 2.5% in animal protein 4. Measured requirements for older men may be higher than current recommendations 5.
Where it turns
Inherited blocks downstream leave methionine or homocysteine to accumulate: classical homocystinuria causes dislocated lenses, skeletal changes and clots, and very high methionine can damage the brain’s white matter 6,7.
The body copes with too much methionine by burning it through homocysteine; most of what goes wrong happens at that turn.
The molecule
Methionine’s side chain is two carbons, a sulfur atom and a methyl group. The sulfur is a thioether, bonded to carbon on both sides, so unlike cysteine’s it cannot form disulfide bridges; it is nonpolar and usually sits inside proteins 1.
That sulfur is still the molecule’s point of attack. Reactive oxygen species convert it to methionine sulfoxide, which comes in two mirror-image forms at the sulfur, and the cell keeps two families of repair enzymes, one for each form. MSRB1, which reduces one of them, uses selenocysteine at its active site 8.
StereochemistryOne stereocentre, the alpha carbon: natural methionine is L, which for methionine is S. Feed-grade methionine is the racemic DL mixture, half D, because animals convert the D form 9.
Move across the chart to read the charge at any pH.
Computed from its pKa values (α-carboxyl 2.28, α-amino 9.21) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.
Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.
| 1st ↓ 2nd → | U | C | A | G | 3rd |
|---|---|---|---|---|---|
| U | UUUPhe | UCUSer | UAUTyr | UGUCys | U |
| UUCPhe | UCCSer | UACTyr | UGCCys | C | |
| UUALeu | UCASer | UAAStop | UGAStop | A | |
| UUGLeu | UCGSer | UAGStop | UGGTrp | G | |
| C | CUULeu | CCUPro | CAUHis | CGUArg | U |
| CUCLeu | CCCPro | CACHis | CGCArg | C | |
| CUALeu | CCAPro | CAAGln | CGAArg | A | |
| CUGLeu | CCGPro | CAGGln | CGGArg | G | |
| A | AUUIle | ACUThr | AAUAsn | AGUSer | U |
| AUCIle | ACCThr | AACAsn | AGCSer | C | |
| AUAIle | ACAThr | AAALys | AGAArg | A | |
| AUGMet | ACGThr | AAGLys | AGGArg | G | |
| G | GUUVal | GCUAla | GAUAsp | GGUGly | U |
| GUCVal | GCCAla | GACAsp | GGCGly | C | |
| GUAVal | GCAAla | GAAGlu | GGAGly | A | |
| GUGVal | GCGAla | GAGGlu | GGGGly | G |
Where it comes from
Methionine is essential: it has to be eaten. What the body does with it is recycle the backbone and pass the sulfur on. Requirements are therefore stated for the two sulfur amino acids together, 15 mg per kilogram per day for adults 10, because cysteine made from methionine is cysteine the diet need not supply.
Direct measurements in adults over 60 found that with plenty of cysteine on board, the minimum methionine need was 5.1 mg/kg/day in both sexes 11. Without cysteine, the total sulfur requirement came out at 26.2 mg/kg/day in men and 17.1 in women, so older men may need substantially more than current recommendations allow 5.
Animal protein is richer in it than plant protein: measured directly, about 2.5% of animal protein against about 1.0% of plant protein isolates, and 2.0% of human muscle protein 4.
EssentialHumans cannot make methionine’s carbon and sulfur skeleton from scratch; the cycle only recycles it. Cysteine can cover part of the need: requirements are given for methionine and cysteine together, 15 mg/kg/day 10, and with plenty of cysteine the minimum methionine need fell to 5.1 mg/kg/day in older adults 11.
In the bottle · syntheticMost methionine sold, overwhelmingly for animal feed, is DL-methionine made by chemical synthesis; pharmaceutical-grade L-methionine is separated from it by enzymatic resolution 9. Fermentation without genetic modification has never exceeded about 5 g per litre, and the best reported L-methionine fermentation, 35 g per litre, uses engineered E. coli 12.
What the body does with it
Methionine starts nearly every protein. The codon AUG is both the instruction for methionine and the signal to begin, so a new protein chain opens with methionine. In bacteria, mitochondria and chloroplasts the starting methionine carries an extra formyl group; in the cytoplasm of human cells and in archaea it does not 13. Human mitochondria keep the bacterial habit, and children with mutations in MTFMT, the enzyme that formylates it, develop Leigh syndrome, a severe failure of mitochondrial energy production 14.
Its second career is as S-adenosylmethionine, SAMe, made by joining methionine to ATP. SAMe is the cell’s methyl donor: it methylates DNA and histones, which changes which genes are read, and makes creatine, phosphatidylcholine, adrenaline and many more 2,15. Every methyl group it gives away leaves S-adenosylhomocysteine behind, which is then cut to homocysteine 1.
Because the diet sets how much methionine reaches cells, it can set how much SAMe there is, and methionine sits at a junction of methylation, antioxidant defence through cysteine and glutathione, polyamines and folate metabolism 2. That is why it keeps appearing in studies of ageing and cancer.
In three sentences each
The universal methyl donor
Methionine adenosyltransferase joins methionine to ATP to make S-adenosylmethionine, SAMe, whose methyl group is handed on by methyltransferases to DNA, histones and small molecules; the remainder is S-adenosylhomocysteine, then homocysteine 1,2.
Two exits from homocysteine
Homocysteine is either rebuilt into methionine, by methionine synthase with vitamin B12 and folate or by betaine, or committed to cysteine through cystathionine β-synthase, which needs vitamin B6 and is switched on by SAMe itself 1,3.
Oxidised, then repaired
The sulfur in methionine is easily oxidised to methionine sulfoxide, and the cell runs dedicated enzymes, the methionine sulfoxide reductases, to reverse it; one of them is a selenoprotein 8.
How it is made, moved and broken down
The liver handles excess methionine with two enzymes most tissues lack: the MAT I/III form of methionine adenosyltransferase, and glycine N-methyltransferase, which spends SAMe on making sarcosine simply to get rid of methyl groups. Lose either and methionine rises in the blood 1.
Homocysteine is the turning point. It can be rebuilt into methionine by methionine synthase, which uses methylcobalamin, the B12 form, and a methyl group from 5-methyltetrahydrofolate, the folate form 3; or by betaine-homocysteine methyltransferase in liver and kidney. Or it can be committed to transsulfuration: cystathionine β-synthase, a vitamin B6 enzyme switched on by SAMe, joins it to serine, and cystathionine γ-lyase cuts the product into cysteine 1.
From cysteine the sulfur goes to taurine and sulfate, or briefly to hydrogen sulfide, a signalling gas that is promptly oxidised 1. More than a dozen inherited disorders sit on this network, at every step from methionine’s activation to sulfide disposal 7.
Carbon skeleton · glucogenicIts carbons end as propionyl-CoA and then succinyl-CoA, so they can make glucose; its sulfur ends in cysteine, taurine and sulfate 1.
- Methionine
- Methionine adenosyltransferaseMAT1A, MAT2A · ATP
- S-Adenosylmethionine
- Methyltransferasese.g. GNMT, DNMT1 · gives a methyl group
- S-Adenosylhomocysteine
- SAH hydrolaseAHCY
- Homocysteine
- Methionine synthaseMTR · vitamin B12, 5-methyl-THF
- Methionine
- Homocysteine
- Cystathionine β-synthaseCBS · vitamin B6, + serine
- Cystathionine
- Cystathionine γ-lyaseCTH · vitamin B6
- Cysteine
- Cysteine dioxygenaseCDO1 · iron
- Taurine or sulfate
Where it matters most
- Liver
- Carries the high-capacity MAT I/III and glycine N-methyltransferase that dispose of excess methionine, and does most transsulfuration 1.
- Mitochondria
- Start their own proteins with formylmethionine, a bacterial inheritance; losing the formylating enzyme causes Leigh syndrome 14.
- Eye, bone and blood vessels
- The tissues classical homocystinuria damages: dislocated lenses, a tall slender skeleton, and clots in veins and arteries 6.
When it goes wrong
Inherited
Classical homocystinuria
CBS · autosomal recessive
Homocysteine and methionine accumulate. Severe cases present in childhood with dislocated lenses, learning difficulty and skeletal changes; mild cases present as adults with thrombosis and often respond to vitamin B6 6. Treatment is a low-methionine diet, betaine and B6 as appropriate, with the aim of keeping total homocysteine below about 100 µmol/L 6.
How it is foundPlasma total homocysteine; newborn screening by methionine catches it unreliably 6,16.
Inherited
Isolated hypermethioninaemia (MAT I/III deficiency)
MAT1A · usually recessive; one common dominant variant (R264H)
The commonest genetic cause of persistently high methionine found by newborn screening; most children are well and their levels drift down 17. At very high levels, above about 800 µmol/L, it can damage the brain’s white matter 7.
How it is foundNewborn screening methionine, normal homocysteine, then MAT1A sequencing 17.
Inherited
Remethylation disorders
MTHFR, MTR, MTRR, cbl genes · autosomal recessive
Homocysteine cannot be turned back into methionine, so homocysteine is high and methionine low; severe MTHFR deficiency responds to early betaine, which is why screening for it is recommended 7,18.
How it is foundHigh total homocysteine with low methionine 18.
Biomarker
Homocysteine and cardiovascular disease
Raised homocysteine is associated with heart attack and stroke, but lowering it with B vitamins in 15 trials of 71,422 people did not reduce heart attacks or deaths; stroke fell slightly (risk ratio 0.90) 19.
How it is foundPlasma total homocysteine 20.
Inherited
Leigh syndrome from failed formylation
MTFMT · autosomal recessive
Without the enzyme that formylates the mitochondrial starting methionine, mitochondrial protein synthesis falters and children develop Leigh syndrome with combined respiratory chain deficiency 14.
How it is foundGenetic testing; respiratory chain studies 14.
How it is measured
Methionine itself is rarely the useful number. Homocysteine is: it reflects whether the cycle is turning and whether B12, folate and B6 are adequate, and expert guidance covers how to draw it, because handling alters it 20.
- Plasma total homocysteineThe functional readout of the methionine cycle, and the test for homocystinuria and for B12 and folate deficiency 19,20.The test actually ordered, far more often than methionine itself 20.Well standardised, with established methods and reference intervals 20.Homocysteine keeps leaking out of red cells after the blood is drawn, so a sample left unspun gives a falsely high result; fasting state, kidney function and B vitamins all move it 20.
- Plasma amino acids (methionine)Methionine is measured in the plasma amino acid profile and in newborn blood spots 18.Accurate as a measurement; poor as a screen. Methionine rises late in classical homocystinuria, so babies are missed 16,18.In Kentucky, of three children with classical homocystinuria among 827,083 screened, newborn screening caught one 16.
- Newborn screening, two-tierMethionine or the methionine-to-phenylalanine ratio first, then total homocysteine on the same blood spot 18.In Qatar a two-tier strategy found all 30 affected babies among 125,047 screened 21.Only 9 of 22 programmes surveyed used homocysteine as the second tier, so practice lags the recommendation 22.
Food, supplements and the evidence
Establishedreplicated in people, for a named outcome
Uncertainsmall, short, mixed, surrogate or preclinical
- Methionine restriction for healthy ageing: strong in rodents 23,24, conditional in flies 25, early and small in people 26.
- In adults with overweight, eight weeks of sulfur amino acid restriction to about 2 g a day changed sulfur metabolism, and the change tracked fat loss; one trial 27.
- Methionine restriction alongside cancer treatment: effective in mouse models, untested in outcome trials 28.
Sold asthe claim on the label, against the evidence
What is strange about it
Cutting methionine in a rat’s diet from 0.86% to 0.17% made male rats live 30% longer, while abolishing their growth 23. Mice show the same direction 24, but in fruit flies it extended life only when other amino acids were scarce 25, so the claim that it works in every species tried is too strong. Human diets that do it are unpalatable, have side effects, and as of 2026 are being tested only in early, small trials 26.
Many cancer cells will not grow when methionine is replaced by homocysteine, even though they can make methionine from homocysteine perfectly well. This is the Hoffman effect, and it says the cells need a methionine flux, not merely methionine 29. In mice, restricting dietary methionine made chemotherapy and radiation work better in resistant colorectal cancer and sarcoma models 28; that is preclinical.
Where it connects
In the Atlas
Topics on the map
On the map
A star in The essential amino acids, one of 14. Every protein starts with it, and restricting it extends life in rats, mice and flies. No trial has measured lifespan in people.
Sources
29 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.
- 1Stipanuk MH. Metabolism of sulfur-containing amino acids: how the body copes with excess methionine, cysteine, and sulfide.doi:10.1093/jn/nxaa094 · PMID 33000151
Review of how the body handles excess methionine: MAT I/III and GNMT in liver, transmethylation to homocysteine, CBS activated by SAMe, cysteine to taurine and sulfate.
- 2Sanderson SM, Gao X, Dai Z, Locasale JW. Methionine metabolism in health and cancer: a nexus of diet and precision medicine.doi:10.1038/s41568-019-0187-8 · PMID 31515518
Review: methylation, redox, polyamines and folate, and how diet sets cellular methionine.
- 3Froese DS, Fowler B, Baumgartner MR. Vitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation.doi:10.1002/jimd.12009 · PMID 30693532
Methionine synthase, methylcobalamin and the folate cycle.
- 4Gorissen SHM, Crombag JJR, Senden JMG, et al. Protein content and amino acid composition of commercially available plant-based protein isolates.doi:10.1007/s00726-018-2640-5 · PMID 30167963
Methionine 1.0% in plant isolates, 2.5% in animal protein, 2.0% in muscle.
- 5Paoletti A, Pencharz PB, Ball RO, et al. The dietary requirement for total sulfur amino acids in adults aged ≥60 years appears to be higher in males than in females.doi:10.1016/j.ajcnut.2023.06.015 · PMID 37356549
Indicator amino acid oxidation in 15 older adults: 26.2 mg/kg/day men, 17.1 women. Small study.
- 6Morris AAM, Kožich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency.doi:10.1007/s10545-016-9979-0 · PMID 27778219
The guideline: presentations, pyridoxine responsiveness, homocysteine targets; evidence quality poor, as for most rare diseases.
- 7Kožich V, Stabler S. Lessons learned from inherited metabolic disorders of sulfur-containing amino acids metabolism.doi:10.1093/jn/nxaa134 · PMID 33000152
Overview of the disorders across the network, including white-matter injury at very high methionine.
- 8Tarrago L, Kaya A, Kim HY, et al. The selenoprotein methionine sulfoxide reductase B1 (MSRB1).doi:10.1016/j.freeradbiomed.2022.08.043 · PMID 36084791
Review of methionine oxidation and its repair, including the selenoprotein MSRB1.
- 9Karau A, Grayson I. Amino acids in human and animal nutrition.doi:10.1007/10_2014_269 · PMID 24676880
Industry review: DL-methionine by chemical synthesis, pharmaceutical grade by enzymatic resolution.
- 10Joint WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition.PMID 18330140
International requirements; methionine plus cysteine 15 mg/kg/day.
- 11Paoletti A, Pencharz PB, Ball RO, et al. The minimum methionine requirement for adults aged ≥60 years is the same in males and females.doi:10.3390/nu15194112 · PMID 37836396
With excess cysteine, minimum methionine need 5.1 mg/kg/day; 15 participants.
- 12Willke T. Methionine production—a critical review.doi:10.1007/s00253-014-6156-y · PMID 25381187
No more than 5 g/L by fermentation without GMOs; 35 g/L with engineered E. coli.
- 13Ramesh V, Köhrer C, RajBhandary UL. Expression of Escherichia coli methionyl-tRNA formyltransferase in Saccharomyces cerevisiae leads to formylation of the cytoplasmic initiator tRNA and possibly to initiation of protein synthesis with formylmethionine.doi:10.1128/MCB.22.15.5434-5442.2002 · PMID 12101237
States the distinction: cytoplasm and archaea start with methionine, bacteria and organelles with formylmethionine.
- 14Tucker EJ, Hershman SG, Köhrer C, et al. Mutations in MTFMT underlie a human disorder of formylation causing impaired mitochondrial translation.doi:10.1016/j.cmet.2011.07.010 · PMID 21907147
Two children with Leigh syndrome; the first human disorder of formylation.
- 15Xiao Z, Locasale JW. Epigenomic links from metabolism—methionine and chromatin architecture.doi:10.1016/j.cbpa.2021.01.011 · PMID 33667809
Review of how methionine metabolism shapes chromatin modification.
- 16Asamoah A, Wei S, Jackson KE, et al. Diagnosis of classic homocystinuria in two boys presenting with acute cerebral venous thrombosis and neurologic dysfunction after normal newborn screening.doi:10.3390/ijns7030048 · PMID 34449521
Case report and screening audit: methionine is a poor screening target.
- 17Chadwick S, Fitzgerald K, Weiss B, Ficicioglu C. Thirteen patients with MAT1A mutations detected through newborn screening: 13 years’ experience.doi:10.1007/8904_2013_286 · PMID 24445979
MAT I/III deficiency as the commonest cause of persistent isolated hypermethioninaemia; the dominant R264H variant.
- 18Huemer M, Kožich V, Rinaldo P, et al. Newborn screening for homocystinurias and methylation disorders: systematic review and proposed guidelines.doi:10.1007/s10545-015-9830-z · PMID 25762406
Recommends screening for CBS and severe MTHFR deficiency, with homocysteine as a second tier.
- 19Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events.doi:10.1002/14651858.CD006612.pub5 · PMID 28816346
Fifteen trials, 71,422 people: no effect on heart attack or death; a small reduction in stroke.
- 20Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion.doi:10.1373/clinchem.2003.021634 · PMID 14709635
Methods, sample handling, reference intervals and clinical use of total homocysteine.
- 21Okun JG, Gan-Schreier H, Ben-Omran T, et al. Newborn screening for vitamin B6 non-responsive classical homocystinuria: systematical evaluation of a two-tier strategy.doi:10.1007/8904_2016_556 · PMID 27325427
Qatar, 125,047 newborns: a two-tier strategy detected all 30 cases.
- 22Keller R, Chrastina P, Pavlíková M, et al. Newborn screening for homocystinurias: recent recommendations versus current practice.doi:10.1002/jimd.12034 · PMID 30740731
Survey: only 9 of 22 programmes used total homocysteine as the second tier.
- 23Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span.doi:10.1093/jn/123.2.269 · PMID 8429371
Male F344 rats on 0.17% methionine lived 30% longer; growth abolished.
- 24Miller RA, Buehner G, Chang Y, et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance.doi:10.1111/j.1474-9726.2005.00152.x · PMID 15924568
Mouse lifespan extension by methionine restriction.
- 25Lee BC, Kaya A, Ma S, et al. Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status.doi:10.1038/ncomms4592 · PMID 24710037
In flies the effect depended on the rest of the diet.
- 26Parkhitko AA, Pathak S, Johnson JE, et al. Methionine restriction and mimetics to ameliorate human aging and disease.doi:10.1016/j.tem.2025.09.006 · PMID 41053925
Review: palatability, side effects and early-stage human trials.
- 27Olsen T, Vinknes KJ, Barvíková K, et al. Dietary sulfur amino acid restriction in humans with overweight and obesity: evidence of an altered plasma and urine sulfurome, and a novel metabolic signature that correlates with loss of fat mass and adipose tissue gene expression.doi:10.1016/j.redox.2024.103192 · PMID 38776754
Fifty-nine adults, eight weeks: changed sulfur metabolism tracking fat loss.
- 28Gao X, Sanderson SM, Dai Z, et al. Dietary methionine influences therapy in mouse cancer models and alters human metabolism.doi:10.1038/s41586-019-1437-3 · PMID 31367041
Methionine restriction improved chemotherapy and radiation responses in mouse models. Preclinical for outcomes.
- 29Kaiser P. Methionine dependence of cancer.doi:10.3390/biom10040568 · PMID 32276408
Review of the Hoffman effect.
This is education, not medical advice. Nothing on this page is written with knowledge of your history, your medications or your risks, and nothing here is a dose. Do not start or stop any treatment on the basis of it — talk to your own physician. Read the full medical disclaimer.