Cysteine (symbol Cys or C) (/ˈsɪstɪiːn/) is a
semi-essential proteinogenic amino acid with the formula
HO2CCH(NH2)CH2SH. It is encoded by the codons UGU and UGC. The thiol
side chain in cysteine often participates in enzymatic reactions, as a
nucleophile. The thiol is susceptible to oxidation to give the
disulfide derivative cystine, which serves an important structural
role in many proteins. When used as a food additive, it has the
E number E920.
Cysteine has the same structure as serine, but with one of its oxygen
atoms replaced by sulfur; replacing it with selenium gives
selenocysteine. (Like other natural proteinogenic amino acids cysteine
has (L) chirality in the older D/L notation based on homology to D and
L glyceraldehyde. In the newer R/S system of designating chirality,
based on the atomic numbers of atoms near the asymmetric carbon,
cysteine (and selenocysteine) have R chirality, because of the
presence of sulfur (resp. selenium) as a second neighbor to the
asymmetric carbon. The remaining chiral amino acids, having lighter
atoms in that position, have S chirality.)
1 Dietary sources
2 Industrial sources
4 Biological functions
4.1 Precursor to the antioxidant glutathione
4.2 Precursor to iron-sulfur clusters
4.3 Metal ion binding
4.4 Roles in protein structure
5.1 Reducing toxic effects of alcohol
7 Dietary restrictions
8 See also
10 External links
Although classified as a non-essential amino acid, in rare cases,
cysteine may be essential for infants, the elderly, and individuals
with certain metabolic disease or who suffer from malabsorption
Cysteine can usually be synthesized by the human body under
normal physiological conditions if a sufficient quantity of methionine
Cysteine is catabolized in the gastrointestinal tract
and blood plasma. In contrast, cystine travels safely
through the GI tract and blood plasma and is promptly reduced to the
two cysteine molecules upon cell entry.
Cysteine is found in most high-protein foods, including:
Animal sources: meat (including pork and poultry), eggs, dairy;
Plant sources: red peppers, garlic, onions, broccoli, brussels sprout,
oats, wheat germ, sprouted lentils.[unreliable source?]
Like other amino acids, cysteine has an amphoteric character.
Cysteine (left) and (S)-
Cysteine (right) in zwitterionic form at
The majority of L-cysteine is obtained industrially by hydrolysis of
animal materials, such as poultry feathers or hog hair. Despite
widespread belief otherwise, there is little evidence that human hair
is used as a source material and its use is explicitly banned in the
European Union. Synthetically produced L-cysteine, compliant with
Jewish kosher and Muslim halal laws, is also available, albeit at a
higher price. The synthetic route involves fermentation using a
mutant of E. coli.
Degussa introduced a route from substituted
thiazolines. Following this technology, L-cysteine is produced by
the hydrolysis of racemic 2-amino-Δ2-thiazoline-4-carboxylic acid
using Pseudomonas thiazolinophilum.
Cystathionine beta synthase
Cystathionine beta synthase catalyzes the upper
reaction and cystathionine gamma-lyase catalyzes the lower reaction.
In animals, biosynthesis begins with the amino acid serine. The sulfur
is derived from methionine, which is converted to homocysteine through
the intermediate S-adenosylmethionine.
then combines homocysteine and serine to form the asymmetrical
thioether cystathionine. The enzyme cystathionine gamma-lyase converts
the cystathionine into cysteine and alpha-ketobutyrate. In plants and
bacteria, cysteine biosynthesis also starts from serine, which is
converted to O-acetylserine by the enzyme serine transacetylase. The
enzyme O-acetylserine (thiol)-lyase, using sulfide sources, converts
this ester into cysteine, releasing acetate.
The cysteine sulfhydryl group is nucleophilic and easily oxidized. The
reactivity is enhanced when the thiol is ionized, and cysteine
residues in proteins have pKa values close to neutrality, so are often
in their reactive thiolate form in the cell. Because of its high
reactivity, the sulfhydryl group of cysteine has numerous biological
Precursor to the antioxidant glutathione
Due to the ability of thiols to undergo redox reactions, cysteine has
antioxidant properties. Cysteine's antioxidant properties are
typically expressed in the tripeptide glutathione, which occurs in
humans as well as other organisms. The systemic availability of oral
glutathione (GSH) is negligible; so it must be biosynthesized from its
constituent amino acids, cysteine, glycine and glutamic acid. Glutamic
acid and glycine are readily available in most Western diets, but the
availability of cysteine can be the limiting substrate.[citation
Precursor to iron-sulfur clusters
Cysteine is an important source of sulfide in human metabolism. The
sulfide in iron-sulfur clusters and in nitrogenase is extracted from
cysteine, which is converted to alanine in the process.
Metal ion binding
Beyond the iron-sulfur proteins, many other metal cofactors in enzymes
are bound to the thiolate substituent of cysteinyl residues. Examples
include zinc in zinc fingers and alcohol dehydrogenase, copper in the
blue copper proteins, iron in cytochrome P450 and nickel in the
[NiFe]-hydrogenases. The sulfhydryl group also has a high affinity
for heavy metals, so that proteins containing cysteine, such as
metallothionein, will bind metals such as mercury, lead and cadmium
Roles in protein structure
In the translation of messenger RNA molecules to produce polypeptides,
cysteine is coded for by the UGU and UGC codons.
Cysteine has traditionally been considered to be a hydrophilic amino
acid, based largely on the chemical parallel between its sulfhydryl
group and the hydroxyl groups in the side-chains of other polar amino
acids. However, the cysteine side chain has been shown to stabilize
hydrophobic interactions in micelles to a greater degree than the side
chain in the non-polar amino acid glycine and the polar amino acid
serine. In a statistical analysis of the frequency with which
amino acids appear in different chemical environments in the
structures of proteins, free cysteine residues were found to associate
with hydrophobic regions of proteins. Their hydrophobic tendency was
equivalent to that of known non-polar amino acids such as methionine
and tyrosine (tyrosine is polar aromatic but also hydrophobic),
those of which were much greater than that of known polar amino acids
such as serine and threonine. Hydrophobicity scales, which rank
amino acids from most hydrophobic to most hydrophilic, consistently
place cysteine towards the hydrophobic end of the spectrum, even when
they are based on methods that are not influenced by the tendency of
cysteines to form disulfide bonds in proteins. Therefore, cysteine is
now often grouped among the hydrophobic amino acids, though it
is sometimes also classified as slightly polar, or polar.
While free cysteine residues do occur in proteins, most are covalently
bonded to other cysteine residues to form disulfide bonds. Disulfide
bonds play an important role in the folding and stability of some
proteins, usually proteins secreted to the extracellular medium.
Since most cellular compartments are reducing environments, disulfide
bonds are generally unstable in the cytosol with some exceptions as
Cystine (shown here in its neutral form), two cysteines
bound together by a disulfide bond.
Disulfide bonds in proteins are formed by oxidation of the sulfhydryl
group of cysteine residues. The other sulfur-containing amino acid,
methionine, cannot form disulfide bonds. More aggressive oxidants
convert cysteine to the corresponding sulfinic acid and sulfonic acid.
Cysteine residues play a valuable role by crosslinking proteins, which
increases the rigidity of proteins and also functions to confer
proteolytic resistance (since protein export is a costly process,
minimizing its necessity is advantageous). Inside the cell, disulfide
bridges between cysteine residues within a polypeptide support the
protein's tertiary structure.
Insulin is an example of a protein with
cystine crosslinking, wherein two separate peptide chains are
connected by a pair of disulfide bonds.
Protein disulfide isomerases catalyze the proper formation of
disulfide bonds; the cell transfers dehydroascorbic acid to the
endoplasmic reticulum, which oxidises the environment. In this
environment, cysteines are, in general, oxidized to cystine and are no
longer functional as a nucleophiles.
Aside from its oxidation to cystine, cysteine participates in numerous
posttranslational modifications. The nucleophilic sulfhydryl group
allows cysteine to conjugate to other groups, e.g., in prenylation.
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and
caspases, which engage in proteolysis in the apoptotic cycle. Inteins
often function with the help of a catalytic cysteine. These roles are
typically limited to the intracellular milieu, where the environment
is reducing, and cysteine is not oxidized to cystine.
Cysteine, mainly the L-enantiomer, is a precursor in the food,
pharmaceutical and personal-care industries. One of the largest
applications is the production of flavors. For example, the reaction
of cysteine with sugars in a
Maillard reaction yields meat
Cysteine is also used as a processing aid for
In the field of personal care, cysteine is used for permanent wave
applications, predominantly in Asia. Again, the cysteine is used for
breaking up the disulfide bonds in the hair's keratin.
Cysteine is a very popular target for site-directed labeling
experiments to investigate biomolecular structure and dynamics.
Maleimides will selectively attach to cysteine using a covalent
Site-directed spin labeling
Site-directed spin labeling for EPR or paramagnetic
relaxation enhanced NMR also uses cysteine extensively.
In a 1994 report released by five top cigarette companies, cysteine is
one of the 599 additives to cigarettes. Like most cigarette additives,
however, its use or purpose is unknown. Its inclusion in
cigarettes could offer two benefits: acting as an expectorant, since
smoking increases mucus production in the lungs; or increasing the
beneficial antioxidant glutathione (which is diminished in smokers).
Reducing toxic effects of alcohol
Cysteine has been proposed as a preventative or antidote for some of
the negative effects of alcohol, including liver damage and hangover.
It counteracts the poisonous effects of acetaldehyde. Cysteine
supports the next step in metabolism, which turns acetaldehyde into
the relatively harmless acetic acid. In a rat study, test animals
received an LD50 dose of acetaldehyde. Those that received cysteine
had an 80% survival rate; when both cysteine and thiamine were
administered, all animals survived. No direct evidence indicates
its effectiveness in humans who consume alcohol at low levels.
N-Acetyl-L-cysteine is a derivative of cysteine wherein an acetyl
group is attached to the nitrogen atom. This compound is sold as a
dietary supplement, and used as an antidote in cases of acetaminophen
Cysteine is required by sheep to produce wool: It is an essential
amino acid that must be taken in from their feed. As a consequence,
during drought conditions, sheep produce less wool; however,
transgenic sheep that can make their own cysteine have been
The animal-originating sources of L-cysteine as a food additive are a
point of contention for people following dietary restrictions such as
Kosher, Halal, Vegan or Vegetarian. To avoid this problem,
L-cysteine can also be sourced from microbial or other synthetic
Wikimedia Commons has media related to Cysteine.
^ Belitz, H.-D; Grosch, Werner; Schieberle, Peter (2009-02-27). Food
Chemistry. ISBN 9783540699330
^ Weast, Robert C., ed. (1981). CRC Handbook of Chemistry and Physics
(62nd ed.). Boca Raton, FL: CRC Press. p. C-259.
ISBN 0-8493-0462-8. .
^ "Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB
Recommendations 1983)", Pure Appl. Chem., 56 (5): 595–624, 1984,
^ a b "The primary structure of proteins is the amino acid sequence".
The Microbial World. University of Wisconsin-Madison Bacteriology
Department. Retrieved 16 September 2012.
^ "Cysteine". University of Maryland Medical Center.
^ "Lentils, sprouted, raw". bitterpoison.com.
^ "EU Chemical Requirements".
^ "Questions About Food Ingredients: What is
L-cysteine/cysteine/cystine?". Vegetarian Resource Group.
^ Martens, Jürgen; Offermanns, Heribert; Scherberich, Paul (1981).
"Facile Synthesis of Racemic Cysteine". Angewandte Chemie
International Edition in English. 20 (8): 668.
^ Drauz, Karlheinz; Grayson, Ian; Kleemann, Axel; Krimmer, Hans-Peter;
Leuchtenberger, Wolfgang; Weckbecker, Christoph (2007). "Amino Acids".
Ullmann's Encyclopedia of Industrial Chemistry.
doi:10.1002/14356007.a02_057.pub2. ISBN 3-527-30673-0.
^ Hell R (1997). "Molecular physiology of plant sulfur metabolism".
Planta. 202 (2): 138–48. doi:10.1007/s004250050112.
^ Bulaj G, Kortemme T, Goldenberg DP (June 1998).
"Ionization-reactivity relationships for cysteine thiols in
polypeptides". Biochemistry. 37 (25): 8965–72.
doi:10.1021/bi973101r. PMID 9636038.
^ Lill R, Mühlenhoff U (2006). "Iron-sulfur protein biogenesis in
eukaryotes: components and mechanisms". Annu. Rev. Cell Dev. Biol. 22:
^ Lippard, Stephen J.; Berg, Jeremy M. (1994). Principles of
Bioinorganic Chemistry. Mill Valley, CA: University Science Books.
ISBN 0-935702-73-3. [page needed]
^ Baker DH, Czarnecki-Maulden GL (June 1987). "Pharmacologic role of
cysteine in ameliorating or exacerbating mineral toxicities". J. Nutr.
117 (6): 1003–10. PMID 3298579.
^ Heitmann P (January 1968). "A model for sulfhydryl groups in
proteins. Hydrophobic interactions of the cystein side chain in
micelles". Eur. J. Biochem. 3 (3): 346–50.
doi:10.1111/j.1432-1033.1968.tb19535.x. PMID 5650851.
^ "A Review of Amino Acids (tutorial)". Curtin University.
^ Nagano N, Ota M, Nishikawa K (September 1999). "Strong hydrophobic
nature of cysteine residues in proteins". FEBS Lett. 458 (1): 69–71.
doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.
^ Betts, M.J.; R.B. Russell (2003). "Hydrophobic amino acids". Amino
Acid Properties and Consequences of Substitutions, In: Bioinformatics
for Geneticists. Wiley. Retrieved 2012-09-16.
^ Gorga, Frank R. (1998–2001). "Introduction to Protein
Structure--Non-Polar Amino Acids". Archived from the original on
2012-09-05. Retrieved 2012-09-16.
^ "Virtual Chembook--Amino Acid Structure". Elmhurst College. Archived
from the original on 2012-10-02. Retrieved 2012-09-16.
^ Sevier CS, Kaiser CA (November 2002). "Formation and transfer of
disulphide bonds in living cells". Nat. Rev. Mol. Cell Biol. 3 (11):
836–47. doi:10.1038/nrm954. PMID 12415301.
^ Huang, Tzou-Chi; Ho, Chi-Tang. Hui, Y. H.; Nip, Wai-Kit; Rogers,
Robert, eds. "
Meat Science and Applications, ch. Flavors of Meat
Products". CRC: 71–102. ISBN 978-0-203-90808-2.
^ "Food Ingredients and Colors". U.S. Food and Drug Administration.
November 2004. Archived from the original on 2009-05-12. Retrieved
2009-09-06 .[dead link]
^ Martin, Terry (2009-06-25). "The List of Additives in Cigarettes".
about.com. Retrieved 2009-09-06. .
^ Sprince H, Parker CM, Smith GG, Gonzales LJ (April 1974).
"Protection against acetaldehyde toxicity in the rat by L-cysteine,
thiamin and L-2-methylthiazolidine-4-carboxylic acid". Agents Actions.
4 (2): 125–30. doi:10.1007/BF01966822. PMID 4842541.
^ Kanter MZ (October 2006). "Comparison of oral and i.v.
acetylcysteine in the treatment of acetaminophen poisoning". Am J
Health Syst Pharm. 63 (19): 1821–7. doi:10.2146/ajhp060050.
^ Powell BC, Walker SK, Bawden CS, Sivaprasad AV, Rogers GE (1994).
Transgenic sheep and wool growth: possibilities and current status".
Reprod. Fertil. Dev. 6 (5): 615–23. doi:10.1071/RD9940615.
Kosher View of L-Cysteine". kashrut.com. May 2003.
Cysteine MS Spectrum
International Kidney Stone Institute
Nagano N, Ota M, Nishikawa K (September 1999). "Strong hydrophobic
nature of cysteine residues in proteins". FEBS Lett. 458 (1): 69–71.
doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.
952-10-3056-9 Interaction of alcohol and smoking in the pathogenesis
of upper digestive tract cancers - possible chemoprevention with
Cystine Kidney Stones
Kosher View of L-Cysteine
Cough and cold preparations (R05)
Guaifenesin (+ oxomemazine)
Ipecacuanha (Syrup of ipecac)
Nerve agent /
see also: Cholinesterase
Digoxin Immune Fab
Primary alcohols: Ethanol
Toxic metals (cadmium
Syrup of ipecac
‡Withdrawn from market
§Never to phase III
The encoded amino acid
Branched-chain amino acids (Valine
Positive charge (pKa)
Negative charge (pKa)
Aspartic acid (≈3.9)
Glutamic acid (≈4.1)
Amino acids types: Encoded (proteins)
Antioxidants & acidity regulators (E300–399)
Thickeners, stabilisers & emulsifiers (E400–499)
pH regulators & anticaking agents (E500–599)
Flavour enhancers (E600–699)
Additional chemicals (E1100–1599)
Synthetic glazes (E910–919)
Improving agents (E920–929)
Packaging gases (E930–949)
Foaming agents (E990–999)
Potassium persulfate (E922)
Ammonium persulfate (E923)
Potassium bromate (E924)
Chlorine dioxide (E926)
Benzoyl peroxide (E928)
Amino acid metabolism metabolic intermediates
β-Hydroxy β-methylbutyric acid
generation of homocysteine: S-Adenosyl methionine
conversion to cysteine: Cystathionine
see urea cycle