The AtlasAmino acidsPolar, uncharged

CysteineCys · C

One of the rarest amino acids in protein, and nearly always at the place where the protein does its work.

Status Reference · not yet an episodeSources 22Reviewed October 2026

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Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · Cys · 7 heavy atoms

Cysteine

C₃H₇NO₂S121.16 g/mol

One of the rarest amino acids in protein, and nearly always at the place where the protein does its work.

Built fromthe charted ones open their own entry

C3CarbonH7Hydrogen N Nitrogen O2Oxygen S Sulphur

Codes: Cys · C
Formula: C₃H₇NO₂S
Molar mass: 121.16 g/mol
Systematic name: (2R)-2-amino-3-sulfanylpropanoic acid
Side chain: Thiomethyl: one carbon and a thiol (–SH); polar, ionisable around pH 8.
Class: Polar, uncharged
In the diet: Conditionally essential
Carbon skeleton: Glucogenic
pKa: α-COOH 1.96 · α-NH₃⁺ 10.28 · side chain 8.18
Isoelectric point: pH 5.07
Hydropathy: +2.5 (Kyte–Doolittle)
Codons: UGU UGC
Main transporters: SLC7A11 (xCT, system xc⁻), SLC3A1, SLC7A9 (rBAT, b0,+AT), CTNS (cystinosin)

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

The amino acid with a thiol: a sulfur carrying a hydrogen at the end of a one-carbon side chain. Two cysteines can lock together as a disulfide bridge, which as a free molecule is called cystine ¹.

Why it matters

Cysteine is the sulfur the body builds glutathione from, its main antioxidant inside cells, and its supply is what limits how fast glutathione is made ². That is the whole logic of N-acetylcysteine, which rescues the liver after a paracetamol overdose by replacing it ³.

Where it runs short

The body can make cysteine from methionine, so the diet does not strictly need it; when methionine runs short, or the conversion fails, cysteine and glutathione fall together ^2,4.

Where it turns

Cystine, the paired form, is barely soluble: in cystinuria the kidney fails to reclaim it and it crystallises into stones, and in cystinosis it is trapped and crystallises inside cells ^5,6.

Its chemistry is its use: the thiol that makes it reactive is the same thiol that makes it hard to keep in solution and hard to measure.

The molecule

Cysteine’s side chain is a single carbon carrying a thiol, an –SH group. Sulfur holds its hydrogen less tightly than oxygen does, so the thiol can lose it to become a negatively charged thiolate, a reactive form that binds metals such as zinc and iron and attacks other molecules. On the free amino acid that happens at a pKa near 8.2; inside a protein, neighbouring charges can lower it by several units, which is how cysteine becomes the working end of so many enzymes ¹.

Two cysteines can be oxidised together into a disulfide bond, a covalent bridge that staples one part of a protein to another. That is why disulfides are common in proteins that leave the cell, such as antibodies and insulin, where the outside world is oxidising, and rare in the reducing interior of the cell ¹. Free cysteine joined this way to a second molecule is cystine, and cystine is strikingly insoluble ⁵.

Cysteine is one of the least common amino acids in proteins, yet it is disproportionately found at catalytic, regulatory and metal-binding sites, conserved through evolution because changing it breaks the protein ¹.

StereochemistryThe one L-amino acid that is R rather than S. Nothing about its shape is different: the Cahn–Ingold–Prelog rules rank substituents by atomic number, and sulfur outranks the oxygens of the carboxyl group, which flips the letter.

Charge · pHCysteine carries almost no net charge at the pH of blood.

Move across the chart to read the charge at any pH.

Computed from its pKa values (α-carboxyl 1.96, α-amino 10.28, side chain 8.18) 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.

HydropathyCysteine scores +2.5: the 5th most water-avoiding of the twenty.

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.

The genetic codeCysteine has 2 codons. The code is redundant, so most single-letter changes at the third position still write cysteine.

The 64 codons of the standard genetic code. Codons for cysteine are marked.
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

The body makes cysteine by transsulfuration. Homocysteine, left over from methionine’s role as a methyl donor, is joined to serine by cystathionine β-synthase, and cystathionine γ-lyase then cuts the product to release cysteine. The sulfur comes from methionine and the carbons from serine, and both enzymes need vitamin B6 ⁴.

Because of this, methionine and cysteine share a single dietary requirement, 15 mg per kilogram per day for adults ⁷. Cysteine in the diet spares methionine: in older adults given plenty of cysteine, the minimum methionine requirement fell to 5.1 mg/kg/day ⁸.

Conditionally essentialMade from methionine’s sulfur and serine’s carbons, so not required in a diet with enough methionine; methionine and cysteine share one requirement, 15 mg/kg/day, and cysteine can supply most of it ^7,8.

How much

Shared with methionine: 15 mg per kilogram per day for adults, which cysteine can largely supply ^7,8.

Where it is in food

Protein-rich foods generally; cysteine content tracks protein, and plant proteins that are low in methionine are often adequate in cysteine ⁸.

In the bottle · naturalMost commercial L-cysteine still comes from keratin, hydrolysed from duck and chicken feathers or human hair with acid, then purified and reduced; fermentation from glucose by engineered bacteria is growing but not yet the main source ^9,10. The product is L-cysteine whichever route made it.

What the body does with it

Glutathione is a three-amino-acid molecule, glutamate, cysteine and glycine, present in every tissue as the most abundant small thiol in the cell. It neutralises peroxides and reactive compounds, carries drugs and toxins out by binding them, and sets the cell’s redox tone ². Its first enzyme, glutamate-cysteine ligase, is rate-limiting, and the supply of cysteine is what limits it ².

That is how N-acetylcysteine saves lives. A paracetamol overdose produces a toxic metabolite that uses up liver glutathione and then attacks the liver itself. Given within eight hours, intravenous N-acetylcysteine gave virtually complete protection against liver damage in a 1979 series of 100 severe poisonings; given after 15 hours it did nothing ³. In the US multicentre study of 2,540 patients, liver injury occurred in 6.1% of those at risk treated within ten hours and in 26.4% treated later ¹¹. It remains the antidote under current US and Canadian consensus guidance ¹².

Cystine is also the cell’s import route for cysteine. The cystine/glutamate antiporter, system xc⁻, brings cystine in; block it with the drug erastin and the cell runs out of glutathione and dies by ferroptosis, a form of death driven by iron and the oxidation of membrane fats ¹³. The enzyme that prevents ferroptosis, GPX4, is a selenoprotein, and its selenocysteine is what keeps it from being permanently oxidised ^14,15. Too much cystine import can kill a cell too: under glucose starvation, cells with high xCT accumulate disulfides in their actin skeleton and die by a separate route named disulfidptosis in 2023 ¹⁶.

In three sentences each

The reactive sulfur

A thiol loses its hydrogen to become a thiolate, a strong nucleophile that grabs metals and attacks other molecules; cysteine’s side chain does this at a pKa of about 8.2, and the protein around it can lower that far enough to make it a catalyst ¹.

Rate-limiting for glutathione

Glutamate-cysteine ligase joins cysteine to glutamate in the first committed step of glutathione synthesis, and the supply of cysteine sets its pace ².

A gate against a kind of death

Cells import cystine in exchange for glutamate through system xc⁻. Block it and glutathione runs out, the selenoprotein GPX4 stops working, and the cell dies by ferroptosis, an iron-dependent oxidative death ^13,14.

How it is made, moved and broken down

Excess cysteine is oxidised by cysteine dioxygenase, an iron enzyme, and the product goes on to taurine or to sulfate, which the kidney excretes. A smaller share is broken down by desulfhydration, which releases hydrogen sulfide, a signalling gas the body quickly oxidises in turn ⁴.

Carbon skeleton · glucogenicIts carbons can end as pyruvate; its sulfur ends as taurine, sulfate, or briefly hydrogen sulfide ⁴.

From methionine to cysteineTranssulfuration: the sulfur is methionine’s, the carbon skeleton serine’s ⁴.

Homocysteine + serine
Cystathionine β-synthaseCBS · vitamin B6
Cystathionine
Cystathionine γ-lyaseCTH · vitamin B6
Cysteine

Glutathione synthesisThe first step is rate-limiting and depends on cysteine supply ².

Cysteine + glutamate
Glutamate-cysteine ligaseGCLC, GCLM · ATP
γ-Glutamylcysteine
Glutathione synthetaseGSS · ATP
Glutathione

Disposal of the sulfurExcess cysteine is oxidised, mostly to taurine and sulfate ⁴.

Cysteine
Cysteine dioxygenaseCDO1 · iron
Cysteine sulfinate
Sulfinoalanine decarboxylaseCSAD · vitamin B6
Hypotaurine → taurine

How it crosses membranes

SLC7A11 · xCT, system xc⁻most cells; imports cystine in exchange for glutamate — the transporter whose blockade triggers ferroptosis ¹³
SLC3A1, SLC7A9 · rBAT, b0,+ATkidney and gut — reclaims cystine with the basic amino acids; mutations cause cystinuria ⁵
CTNS · cystinosinthe lysosome membrane — exports cystine from lysosomes; its loss causes cystinosis ¹⁷

Where it matters most

Liver: Makes most of the body’s glutathione and is where paracetamol toxicity strikes when glutathione runs out ^2,3.
Kidney: Reclaims filtered cystine through rBAT and b0,+AT; when it cannot, cystine stones form ⁵.
Lysosomes, everywhere: Cystine made by protein breakdown has to be exported by cystinosin; without it cystine crystallises inside cells of the kidney, eye, thyroid and muscle ¹⁷.
Hair, skin and nails: Keratin is rich in disulfide-bridged cysteine, which is why hair and feathers are the industrial source of it ⁹.

When it goes wrong

Inherited

Cystinuria

SLC3A1, SLC7A9 · autosomal recessive

The kidney cannot reclaim cystine, and at normal urine pH cystine is so poorly soluble that it forms stones; treatment is high fluid intake, alkalinising the urine and, if needed, thiol drugs that split cystine ⁵. In 130 children followed from birth, 4% of type A/A and 17% of type B/B had stones, and each stone followed months of concentrated urine ¹⁸.

How it is foundUrine cystine; stone analysis; genetic testing ⁵.

Inherited

Nephropathic cystinosis

CTNS · autosomal recessive

Cystine is trapped in lysosomes and crystallises, first wrecking the kidney’s proximal tubule (Fanconi syndrome) in infancy, then the kidney itself and other organs ¹⁷. Cysteamine, which clears about 95% of lysosomal cystine, delays kidney failure by about seven years, to a mean age of 16 ⁶.

How it is foundLeucocyte cystine and CTNS sequencing ^6,17.

Drug

Paracetamol (acetaminophen) poisoning

N-acetylcysteine, a cysteine donor, restores liver glutathione; it is nearly fully protective within eight hours of overdose and loses effect thereafter ^3,11. It remains standard treatment ¹².

How it is foundParacetamol level against time since ingestion, and liver tests ¹².

Association

Ferroptosis in disease and cancer therapy

SLC7A11, GPX4

Cutting cystine supply or inhibiting GPX4 kills some cancer cells by ferroptosis, and diffuse large B-cell lymphomas and kidney cancers were especially sensitive in a screen of 177 cell lines ¹⁴. This is laboratory and animal work; no ferroptosis-inducing drug is approved ^13,14.

How it is foundResearch measures only.

How it is measured

Free cysteine is a difficult analyte. It oxidises in the tube, it exchanges with other thiols, and red cells release thiols when they break, so methods that freeze the state of the sample immediately, by alkylating free thiols, are needed for numbers that mean anything ¹⁹.

Urine cystineThe test for cystinuria: cystine excretion in a timed or spot urine, and in children the parents’ urine helps assign type ^5,18.Diagnostic when clearly raised; levels relative to creatinine fall with age while concentration per litre rises ¹⁸.Concentration, not daily total, predicts stones, and stones were preceded by months of concentrated urine ¹⁸.
Leucocyte cystineCystine measured inside white blood cells, for cystinosis ¹⁷.The cornerstone of both diagnosis and treatment monitoring ¹⁷.Needs specialist handling and a laboratory that offers it; confirmed with CTNS genetic testing ⁶.
Plasma cysteine and cystineFree and total cysteine in plasma, and the ratio of cysteine to cystine as a research index of oxidative stress ¹⁹.Mostly research; clinical practice measures total homocysteine, and urine or leucocyte cystine for the two cystine diseases ^5,17,20.Reproducible with prompt alkylation of the sample and careful handling ¹⁹.Cysteine oxidises after blood is drawn, and haemolysis releases thiols from red cells, so a sample not processed at once gives the wrong answer ¹⁹.

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

N-acetylcysteine is the antidote to paracetamol poisoning, most effective within eight hours ^3,11,12.

Uncertainsmall, short, mixed, surrogate or preclinical

N-acetylcysteine as a general antioxidant: trials in kidney protection from contrast dye and other conditions conflict, and its benefit depends on whether it actually raises glutathione inside cells ²¹.
GlyNAC, glycine with N-acetylcysteine, raised glutathione and improved several markers in 12 older adults over 16 weeks; a small trial ²².

Sold asthe claim on the label, against the evidence

“Take glutathione or cysteine to detox.” The body’s rate of glutathione synthesis is set by an enzyme and its cysteine supply, and supplementing helps where glutathione has been depleted, as in paracetamol poisoning; in healthy people the general antioxidant evidence is conflicting ^2,21.

What is strange about it

Cysteine is the one L-amino acid that is called R rather than S. Nothing about it is the wrong way round: the letter comes from a ranking rule, and sulfur is heavier than the oxygen that decides the letter for the other eighteen.

The cysteine in a bread dough conditioner or a supplement capsule has most likely been made from feathers or human hair, by boiling the keratin in acid. Industry and regulators are moving towards fermentation, but as of 2026 keratin hydrolysis is still the main industrial source ^9,10.

Where it connects

In the Atlas

MetMethionineNonpolar, aliphatic SecSelenocysteineWritten in a stop codon SerSerinePolar, uncharged GlyGlycineNonpolar, aliphatic GluGlutamateNegatively charged SSulfurElement SeSeleniumElement

Topics on the map

On the map

A star in Conditional amino acids, one of 14. The rate-limiting amino acid for glutathione, the sulfur that makes disulfide bonds, and the thing NAC exists to deliver.

Find it on the map

Sources

22 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.

1
Poole LB. The basics of thiols and cysteines in redox biology and chemistry.Free Radic Biol Med · 2015 · 80:148–157doi:10.1016/j.freeradbiomed.2014.11.013 · PMID 25433365
Review of cysteine chemistry: pKa, thiolates, disulfides and functional sites.
2
Lu SC. Glutathione synthesis.Biochim Biophys Acta · 2013 · 1830(5):3143–3153doi:10.1016/j.bbagen.2012.09.008 · PMID 22995213
Glutathione synthesis and its rate-limiting step, set by cysteine supply and GCL activity.
3
Prescott LF, Illingworth RN, Critchley JA, et al. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning.Br Med J · 1979 · 2(6198):1097–1100doi:10.1136/bmj.2.6198.1097 · PMID 519312
One hundred severe poisonings: near-complete protection within eight hours, none after 15. Uncontrolled series with historical comparison.
4
Stipanuk MH. Metabolism of sulfur-containing amino acids: how the body copes with excess methionine, cysteine, and sulfide.J Nutr · 2020 · 150(Suppl 1):2494S–2505Sdoi:10.1093/jn/nxaa094 · PMID 33000151
Transsulfuration and cysteine disposal to taurine, sulfate and hydrogen sulfide.
5
Servais A, Thomas K, Dello Strologo L, et al. Cystinuria: clinical practice recommendation.Kidney Int · 2021 · 99(1):48–58doi:10.1016/j.kint.2020.06.035 · PMID 32918941
European consensus recommendations on diagnosis and treatment.
6
Chang HE, Hossain MS, Song C, et al. Long-term outcomes in nephropathic cystinosis: a review.Pediatr Nephrol · 2025 · 41(2):277–296doi:10.1007/s00467-025-06790-6 · PMID 40369127
Cysteamine depletes ~95% of lysosomal cystine and delays kidney failure by about seven years.
7
Joint WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition.World Health Organ Tech Rep Ser · 2007 · (935):1–265PMID 18330140
Methionine plus cysteine requirement, 15 mg/kg/day.
8
Paoletti A, Pencharz PB, Ball RO, et al. The minimum methionine requirement for adults aged ≥60 years is the same in males and females.Nutrients · 2023 · 15(19):4112doi:10.3390/nu15194112 · PMID 37836396
With excess cysteine the minimum methionine need was 5.1 mg/kg/day; cysteine spares most of the requirement.
9
Caballero Cerbon DA, Gebhard L, Dokuyucu R, et al. Challenges and advances in the bioproduction of L-cysteine.Molecules · 2024 · 29(2):486doi:10.3390/molecules29020486 · PMID 38257399
Industry review: extraction from hair and feathers, and fermentation alternatives.
10
Zhao M, Wu D, Liao Y, et al. Recent advances in L-cysteine bioproduction: biocatalytic strategies and metabolic engineering solutions.Crit Rev Biotechnol · 2026 · 1–21doi:10.1080/07388551.2026.2722960 · PMID 42744659
States that industrial production still mainly relies on keratin hydrolysis.
11
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985).N Engl J Med · 1988 · 319(24):1557–1562doi:10.1056/NEJM198812153192401 · PMID 3059186
2,540 patients: hepatotoxicity 6.1% when treated within ten hours, 26.4% at 10–24 hours.
12
Dart RC, Mullins ME, Matoushek T, et al. Management of acetaminophen poisoning in the US and Canada: a consensus statement.JAMA Netw Open · 2023 · 6(8):e2327739doi:10.1001/jamanetworkopen.2023.27739 · PMID 37552484
Current consensus guidance from four toxicology societies.
13
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death.Cell · 2012 · 149(5):1060–1072doi:10.1016/j.cell.2012.03.042 · PMID 22632970
Named ferroptosis; erastin blocks cystine uptake by system xc⁻. Cell and tissue-slice work.
14
Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4.Cell · 2014 · 156(1–2):317–331doi:10.1016/j.cell.2013.12.010 · PMID 24439385
GPX4 as the central regulator; lymphoma and kidney cancer lines most sensitive.
15
Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis.Cell · 2018 · 172(3):409–422.e21doi:10.1016/j.cell.2017.11.048 · PMID 29290465
Mice: a cysteine version of GPX4 is overoxidised; selenocysteine protects. Animal study.
16
Liu X, Nie L, Zhang Y, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis.Nat Cell Biol · 2023 · 25(3):404–414doi:10.1038/s41556-023-01091-2 · PMID 36747082
Named disulfidptosis, a cell death from disulfide stress in high-xCT cells under glucose starvation. Cell studies.
17
Elmonem MA, Veys KR, Soliman NA, et al. Cystinosis: a review.Orphanet J Rare Dis · 2016 · 11:47doi:10.1186/s13023-016-0426-y · PMID 27102039
Review; leucocyte cystine as the cornerstone of diagnosis and monitoring.
18
Tokhmafshan F, Goodyer PR. Unraveling the natural history of presymptomatic cystinuria.Curr Opin Nephrol Hypertens · 2023 · 32(3):297–304doi:10.1097/MNH.0000000000000880 · PMID 37013453
130 children followed from birth: stone rates by type, and concentration as the predictor.
19
Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo.Free Radic Biol Med · 2009 · 47(10):1329–1338doi:10.1016/j.freeradbiomed.2009.08.021 · PMID 19715755
Method and caveats for plasma cysteine and cystine, including haemolysis.
20
Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion.Clin Chem · 2004 · 50(1):3–32doi:10.1373/clinchem.2003.021634 · PMID 14709635
Clinical measurement of total homocysteine and other thiols.
21
Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits.Pharmacol Ther · 2014 · 141(2):150–159doi:10.1016/j.pharmthera.2013.09.006 · PMID 24080471
Review: antioxidant trials of NAC conflict.
22
Kumar P, Liu C, Suliburk J, et al. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial.J Gerontol A Biol Sci Med Sci · 2023 · 78(1):75–89doi:10.1093/gerona/glac135 · PMID 35975308
Twenty-four older adults randomised, twelve to GlyNAC and twelve to an alanine placebo, for sixteen weeks; improvements in glutathione and other markers. Small, from a single group of investigators.

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