The AtlasAmino acidsPositively charged
LysineLys · K
The limiting amino acid in the world’s grain, the anchor point for collagen’s cross-links and histone marks, and the supplement most often sold for cold sores.
Molecule · Lys · 10 heavy atoms
Lysine
C6H14N2O2146.19 g/mol
The limiting amino acid in the world’s grain, the anchor point for collagen’s cross-links and histone marks, and the supplement most often sold for cold sores.
Built fromthe charted ones open their own entry
- Codes
- Lys · K
- Formula
- C6H14N2O2
- Molar mass
- 146.19 g/mol
- Systematic name
- (2S)-2,6-diaminohexanoic acid
- Side chain
- 4-Aminobutyl: four CH₂ groups ending in an amine; positively charged at the pH of blood.
- Class
- Positively charged
- In the diet
- Essential
- Carbon skeleton
- Ketogenic
- pKa
- α-COOH 2.18 · α-NH3+ 8.95 · side chain 10.53
- Isoelectric point
- pH 9.74
- Hydropathy
- -3.9 (Kyte–Doolittle)
- Codons
AAAAAG- Main transporters
- SLC7A7 (y⁺LAT1, with CD98), SLC3A1, SLC7A9 (rBAT, b⁰,⁺AT)
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
An essential amino acid with a long, flexible four-carbon side chain that ends in a positively charged amino group. It cannot be made in the body 1.
Why it matters
It is the amino acid cereal proteins run out of first, which is why grains and legumes together feed people better than either alone 2,3. In the body its side-chain amine is the place where collagen is cross-linked, histones are marked, and proteins are tagged for destruction 4,5,6.
Where it runs short
In diets built on a single cereal, lysine is what runs short; requirement studies in Indian men put the need at about 30 mg/kg a day, more than double the 1985 estimate, and higher still in undernourished men 7,8.
Where it turns
Lysine is well tolerated as a supplement: a review of 71 studies set a provisional no-observed-adverse-effect level of 6 g a day, with stomach upset the usual complaint above it 9. The serious problems are inherited blocks in its breakdown 10.
In the diet it is the shortfall that matters; in medicine it is the breakdown.
The molecule
Lysine’s side chain is a straight run of four carbons ending in an amino group. That amine has a pKa of about 10.5, so at the pH of blood it is almost always protonated and positive; the long, flexible chain lets it reach out of a protein’s surface into water.
Because that amine is reactive and exposed, it is where much of the cell’s chemistry happens to a protein after it is made. Histone tails are acetylated and methylated on lysines to switch genes on and off 5; ubiquitin is joined to target proteins through an isopeptide bond to a lysine, marking them for destruction or redirecting them 6; and in 2009 mass spectrometry found acetylation on 3,600 lysines in 1,750 proteins, spread across almost every cellular process 11.
Move across the chart to read the charge at any pH.
Computed from its pKa values (α-carboxyl 2.18, α-amino 8.95, side chain 10.53) 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
Lysine is essential. The adult requirement is 30 mg per kilogram a day 1, set after tracer studies showed the 1985 figure of 12 mg/kg was far too low: well-nourished Indian men needed about 31 mg/kg, and chronically undernourished men about 44 7,8.
Plant protein supplies about 65% of the world’s protein, and cereals are low in lysine 2. Mixtures of plant proteins can still meet every requirement 2: moist-cooked sorghum had lysine that was 94% available, and adding lentils improved the meal’s protein value further 3.
EssentialMust come from food; the adult requirement is 30 mg per kilogram a day 1. Indian men on long-term controlled diets needed 31 mg/kg, against the 12 mg/kg set in 1985 7.
In the bottle · fermentedLysine is one of the largest-volume products of industrial fermentation, about 2.2 million tonnes a year, made almost entirely by mutant strains of Corynebacterium glutamicum, most of it for animal feed 12,13. It is the same molecule as in food.
What the body does with it
Collagen and elastin owe their strength to cross-links made from lysine. The five lysyl oxidases, copper-dependent enzymes, oxidise lysine side chains in the assembled fibres, and the resulting aldehydes link neighbouring strands 4. A separate enzyme, lysyl hydroxylase 1, adds a hydroxyl first; its loss causes the kyphoscoliotic form of Ehlers–Danlos syndrome 14,15.
Lysine is also the backbone of carnitine, which carries fatty acids into mitochondria. The body builds carnitine from lysines that have been trimethylated while still part of proteins, and then released when those proteins are broken down 16.
Infused in large amounts, lysine competes with radiolabelled peptides for uptake by the kidney. Given with arginine during radionuclide therapy of neuroendocrine tumours, it cut renal uptake by about a third, with fewer side effects than lysine alone, which raised potassium dangerously in some patients 17.
In three sentences each
The limiting amino acid in cereals
Cereal proteins are low in lysine and legumes are rich in it, so mixtures of plant proteins can meet every requirement; adding lentils to sorghum lowered the indicator of unmet need by 19% in one tracer study 2,3.
A handle for cross-links
Lysyl oxidases, copper enzymes, turn lysine side chains in collagen and elastin into reactive aldehydes, the first step of the cross-links that give these proteins their strength 4.
How it is made, moved and broken down
Lysine is broken down mainly through saccharopine, a pathway confined to mitochondria; a second route through pipecolic acid matters more in the brain, though how much is still debated 10,18. Five inherited disorders affect the pathway. Two are severe, pyridoxine-dependent epilepsy and glutaric aciduria type 1; three, including hyperlysinaemia, appear to have no clinical consequences 10,19.
Carbon skeleton · ketogenicBroken down in mitochondria, mostly through saccharopine, to glutaryl-CoA and on to acetyl-CoA, so none of its carbon can make glucose 10,20.
- Lysine + 2-oxoglutarate
- α-Aminoadipic semialdehyde synthaseAASS · NADPH
- Saccharopine
- AASS (second domain)AASS · NAD⁺
- α-Aminoadipic semialdehyde
- AntiquitinALDH7A1 · NAD⁺
- α-Aminoadipate
- Glutaryl-CoA dehydrogenaseGCDH · FAD
- Crotonyl-CoA → acetyl-CoA
- Lysine in collagen
- Lysyl oxidaseLOX, LOXL1–4 · copper
- Allysine (an aldehyde)
- Trimethyllysine (from protein)
- Four enzymesTMLHE, BBOX1 · iron, vitamin C
- Carnitine
How it crosses membranes
- SLC7A7 · y⁺LAT1, with CD98the blood side of gut and kidney cells — exports lysine, arginine and ornithine; its loss causes lysinuric protein intolerance 22
- SLC3A1, SLC7A9 · rBAT, b⁰,⁺ATthe gut and kidney lumen — reclaims lysine with cystine and the other basic amino acids; mutations cause cystinuria 23
Where it matters most
When it goes wrong
Inherited
Pyridoxine-dependent epilepsy
ALDH7A1 · autosomal recessive
Seizures, often from birth, that stop with pyridoxine because the accumulating lysine product inactivates vitamin B6 21. Guidelines add a lysine-restricted diet and arginine, but most patients have developmental delay or intellectual disability despite seizure control 24.
How it is foundUrine α-aminoadipic semialdehyde and ALDH7A1 sequencing; blood-spot screening is being tested 24,25.
Inherited
Glutaric aciduria type 1
GCDH · autosomal recessive
Without treatment, an illness or fast in the first years of life can destroy the striatum and leave a severe movement disorder. Newborn screening, a low-lysine diet, carnitine and emergency treatment during illness prevent most of it; the diet can be relaxed after age six 20.
How it is foundGlutarylcarnitine on newborn screening, urine glutaric and 3-hydroxyglutaric acid, GCDH sequencing 20.
Inherited
Lysinuric protein intolerance
SLC7A7 · autosomal recessive
The gut and kidney cannot export lysine, arginine and ornithine, so they are lost and the urea cycle runs short, with hyperammonaemia after protein 22. In a Paris cohort of 16 followed for a mean of 11 years, ten presented with hyperammonaemia, all had kidney disease, and six died, at a mean age of four, of pulmonary alveolar proteinosis 26.
How it is foundPlasma and urine dibasic amino acids, SLC7A7 sequencing 22,26.
Inherited
Hyperlysinaemia
AASS · autosomal recessive
High plasma lysine from loss of the first enzyme of breakdown; generally a benign metabolic variant 19.
How it is foundPlasma lysine and AASS sequencing 19.
Inherited
Kyphoscoliotic Ehlers–Danlos syndrome
PLOD1, FKBP14 · autosomal recessive
Lysyl hydroxylase 1 deficiency disrupts collagen cross-linking, causing low muscle tone at birth, progressive spinal curvature and fragile tissues 14,15.
How it is foundMolecular confirmation, required for every Ehlers–Danlos type except the hypermobile one; an altered urine ratio of lysyl to hydroxylysyl pyridinoline supports the diagnosis 15,27.
How it is measured
Plasma lysine is part of the routine amino acid panel, and like the others it shifts with how the sample is stored and which tube it was drawn into 28. The disease markers are downstream: glutarylcarnitine for glutaric aciduria type 1, and α-aminoadipic semialdehyde and its partners for pyridoxine-dependent epilepsy 20,21,25.
- Plasma amino acidsLysine is measured in the standard plasma amino acid panel, high in hyperlysinaemia and low in lysinuric protein intolerance 19,26.Reliable with prompt handling; heparin plasma was the most stable sample type in one comparison 28.Levels drift with storage time and tube type before analysis 28.
- Urine and blood markers of lysine breakdownGlutarylcarnitine in newborn screening for glutaric aciduria type 1, and α-aminoadipic semialdehyde in urine for pyridoxine-dependent epilepsy 20,21.Newborn screening for glutaric aciduria type 1 is established; for pyridoxine-dependent epilepsy, new blood-spot markers were raised in 7 or 8 of 8 cases in a feasibility study 20,25.Some people with glutaric aciduria type 1 excrete little of the marker and can be missed 20.
Food, supplements and the evidence
Establishedreplicated in people, for a named outcome
Uncertainsmall, short, mixed, surrogate or preclinical
- Lysine for cold sores: one 1987 trial and smaller studies suggest benefit only above about 3 g a day, while a 2015 Cochrane review found no reliable evidence for prevention 29,30,31.
- Lysine-fortified flour lowered anxiety and stress hormones in a three-month trial in Syrian families; the first author worked for a lysine manufacturer 32.
Sold asthe claim on the label, against the evidence
- “Lysine stops cold sores.” The best summary of prevention trials, 32 trials of 19 treatments, found no evidence that lysine works 31.
What is strange about it
Pyridoxine-dependent epilepsy is a lysine disorder that looks like a vitamin deficiency. A lysine breakdown product that builds up when antiquitin fails reacts with the active form of vitamin B6 and inactivates it, so the seizures stop with large doses of pyridoxine 21.
Arginine is used as a drug against a lysine disorder: it competes with lysine for transport, so in pyridoxine-dependent epilepsy it is given with a lysine-restricted diet 24,33.
The trial that launched lysine for cold sores, in 1987, found 2.4 fewer outbreaks over six months on 3 g a day; a 2015 Cochrane review of 32 trials of prevention found no good evidence that lysine works 29,31.
Where it connects
In the Atlas
Topics on the map
On the map
A star in The essential amino acids, one of 14. The limiting amino acid in cereal protein, and the reason a grain and a legume together do what neither does alone.
Sources
33 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.
- 1Joint WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition.PMID 18330140
Lysine, 30 mg/kg/day.
- 2Young VR, Pellett PL. Plant proteins in relation to human protein and amino acid nutrition.doi:10.1093/ajcn/59.5.1203S · PMID 8172124
Plant protein is 65% of world supply; mixtures are complete.
- 3Paoletti A, Fakiha A, Tul-Noor Z, et al. Bioavailable lysine assessed using the indicator amino acid oxidation method in healthy young males is high when sorghum is cooked by a moist cooking method.doi:10.1093/jn/nxab410 · PMID 34871427
Five men; lysine 94% available; lentils lowered indicator oxidation 19%.
- 4Vallet SD, Ricard-Blum S. Lysyl oxidases: from enzyme activity to extracellular matrix cross-links.doi:10.1042/EBC20180050 · PMID 31488698
Five copper enzymes start collagen and elastin cross-linking.
- 5Strahl BD, Allis CD. The language of covalent histone modifications.doi:10.1038/47412 · PMID 10638745
The histone code hypothesis.
- 6Komander D, Rape M. The ubiquitin code.doi:10.1146/annurev-biochem-060310-170328 · PMID 22524316
Ubiquitin joined to lysines by isopeptide bonds.
- 7Kurpad AV, Regan MM, Raj T, et al. Lysine requirements of healthy adult Indian subjects receiving long-term feeding, measured with a 24-h indicator amino acid oxidation and balance technique.doi:10.1093/ajcn/76.2.404 · PMID 12145014
18 men; requirement about 31 mg/kg/day against 12 in 1985.
- 8Kurpad AV, Regan MM, Raj T, et al. Lysine requirements of chronically undernourished adult Indian men, measured by a 24-h indicator amino acid oxidation and balance technique.doi:10.1093/ajcn/77.1.101 · PMID 12499329
27 undernourished men; 44 mg/kg/day.
- 9Hayamizu K, Oshima I, Fukuda Z, et al. Safety assessment of L-lysine oral intake: a systematic review.doi:10.1007/s00726-019-02697-3 · PMID 30661148
71 studies; provisional NOAEL 6 g/day.
- 10Leandro J, Houten SM. The lysine degradation pathway: subcellular compartmentalization and enzyme deficiencies.doi:10.1016/j.ymgme.2020.07.010 · PMID 32768327
Saccharopine and pipecolic pathways; two severe and three benign disorders.
- 11Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions.doi:10.1126/science.1175371 · PMID 19608861
3,600 acetylation sites on 1,750 proteins.
- 12Eggeling L, Bott M. A giant market and a powerful metabolism: L-lysine provided by Corynebacterium glutamicum.doi:10.1007/s00253-015-6508-2 · PMID 25761623
About 2.2 million tonnes a year.
- 13Liu J, Xu JZ, Rao ZM, Zhang WG. Industrial production of L-lysine in Corynebacterium glutamicum: progress and prospects.doi:10.1016/j.micres.2022.127101 · PMID 35803058
Uses in food, medicine and animal feed.
- 14Colman M, Vroman R, Dhooge T, et al. Kyphoscoliotic Ehlers-Danlos syndrome caused by pathogenic variants in FKBP14: further insights into the phenotypic spectrum and pathogenic mechanisms.doi:10.1002/humu.24456 · PMID 36054293
PLOD1 and FKBP14 forms of kEDS.
- 15Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes.doi:10.1002/ajmg.c.31552 · PMID 28306229
Thirteen types; all but hypermobile need molecular confirmation.
- 16Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals.doi:10.1042/0264-6021:3610417 · PMID 11802770
Carnitine from protein-bound trimethyllysine.
- 17Rolleman EJ, Valkema R, de Jong M, et al. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine.doi:10.1007/s00259-002-0982-3 · PMID 12483404
Lysine alone cut renal uptake 44% but raised potassium; with arginine 33%.
- 18Guo Y, Wu J, Guo W. The neuropathological mechanisms underlying the inborn errors of lysine metabolism.doi:10.1016/j.nbd.2026.107315 · PMID 41666987
Which pathway dominates in the brain remains contested.
- 19Houten SM, te Brinke H, Denis S, et al. Genetic basis of hyperlysinemia.doi:10.1186/1750-1172-8-57 · PMID 23570448
AASS variants; a generally benign metabolic variant.
- 20Boy N, Mühlhausen C, Maier EM, et al. Recommendations for diagnosing and managing individuals with glutaric aciduria type 1: third revision.doi:10.1002/jimd.12566 · PMID 36221165
Screening, diet, carnitine and emergency treatment.
- 21Mills PB, Struys E, Jakobs C, et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures.doi:10.1038/nm1366 · PMID 16491085
The lysine product inactivates pyridoxal phosphate.
- 22Torrents D, Mykkänen J, Pineda M, et al. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene.doi:10.1038/6809 · PMID 10080182
The basolateral dibasic amino acid transporter.
- 23Servais A, Thomas K, Dello Strologo L, et al. Cystinuria: clinical practice recommendation.doi:10.1016/j.kint.2020.06.035 · PMID 32918941
rBAT and b⁰,⁺AT reclaim cystine and the basic amino acids.
- 24Coughlin CR, Tseng LA, Abdenur JE, et al. Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency.doi:10.1002/jimd.12332 · PMID 33200442
Pyridoxine, lysine restriction and arginine.
- 25Pauly K, Woontner M, Abdenur JE, et al. Feasibility of newborn screening for pyridoxine-dependent epilepsy.doi:10.1016/j.ymgme.2024.109002 · PMID 39729892
Two blood-spot markers raised in 7 and 8 of 8 cases; small study.
- 26Mauhin W, Habarou F, Gobin S, et al. Update on lysinuric protein intolerance, a multi-faceted disease: retrospective cohort analysis from birth to adulthood.doi:10.1186/s13023-016-0550-8 · PMID 28057010
16 patients followed from birth.
- 27Conti R, Zanchi C, Barbi E. A floppy infant without lingual frenulum and kyphoscoliosis: Ehlers Danlos syndrome case report.doi:10.1186/s13052-021-00984-y · PMID 33579342
Case report; the urine pyridinoline ratio.
- 28Xia T, Gao S, Shu C, et al. Analysis of amino acids in human blood using UHPLC-MS/MS: potential interferences of storage time and vacutainer tube in pre-analytical procedure.doi:10.1016/j.clinbiochem.2016.09.018 · PMID 27693603
25 people; heparin plasma most stable.
- 29Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection: treatment and prophylaxis.PMID 3115841
1 g three times a day for six months; 27 against 25 completers.
- 30Mailoo VJ, Rampes S. Lysine for herpes simplex prophylaxis: a review of the evidence.PMID 30881246
Below 1 g/day ineffective; above 3 g/day possibly helpful; longer trials needed.
- 31Chi CC, Wang SH, Delamere FM, et al. Interventions for prevention of herpes simplex labialis (cold sores on the lips).doi:10.1002/14651858.CD010095.pub2 · PMID 26252373
32 trials, 2,640 people; no evidence for lysine.
- 32Smriga M, Ghosh S, Mouneimne Y, et al. Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria.doi:10.1073/pnas.0402550101 · PMID 15159538
Three-month randomised trial; first author affiliated with a lysine manufacturer.
- 33Jafari A, Abbasi MM, Abbasi H, et al. Combination therapy with pyridoxine and arginine supplementations along with a lysine-restricted diet in individuals with pyridoxine-dependent epilepsy: a comprehensive systematic review.doi:10.1016/j.cdnut.2025.107504 · PMID 40800672
38 observational studies; early triple therapy looked best.
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