Cysteine (symbol Cys or C; ) is a semiessential
proteinogenic amino acid with the
formula
In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...
. The
thiol side chain in cysteine often participates in
enzymatic reactions as a
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
.
When present as a
deprotonated catalytic
residue, sometimes the symbol Cyz is used. The deprotonated form can generally be described by the symbol Cym as well.
The thiol is susceptible to oxidation to give the
disulfide derivative
cystine, which serves an important structural role in many
proteins. In this case, the symbol Cyx is sometimes used.
When used as a food additive, it has the
E number
E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
E920.
Cysteine is
encoded by the
codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s UGU and UGC.
The sulfur-containing amino acids cysteine and
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
are more easily oxidized than the other amino acids.
Structure
Like other amino acids (not as a residue of a protein), cysteine exists as a
zwitterion. Cysteine has
chirality
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
in the older / notation based on homology to - and -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 (or selenium) as a second neighbor to the asymmetric carbon atom. The remaining chiral amino acids, having lighter atoms in that position, have ''S'' chirality. Replacing sulfur with
selenium gives
selenocysteine
Selenocysteine (symbol Sec or U, in older publications also as Se-Cys) is the 21st proteinogenic amino acid. Selenoproteins contain selenocysteine residues. Selenocysteine is an analogue of the more common cysteine with selenium in place of the s ...
.
Dietary sources
Cysteinyl is a residue in high-
protein foods. Although classified as a non
essential amino acid, in rare cases, cysteine may be essential for infants, the elderly, and individuals with certain metabolic diseases or who suffer from
malabsorption syndromes. Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
is available.
Industrial sources
The majority of -cysteine is obtained industrially by
hydrolysis of animal materials, such as poultry feathers or hog hair. Despite widespread belief otherwise, little evidence shows that human hair is used as a source material and its use is explicitly banned for food additives and cosmetic products in the European Union. Synthetically produced -cysteine, compliant with Jewish
kosher
(also or , ) is a set of dietary laws dealing with the foods that Jewish people are permitted to eat and how those foods must be prepared according to Jewish law. Food that may be consumed is deemed kosher ( in English, yi, כּשר), fro ...
and Muslim
halal laws, is also available, albeit at a higher price. The synthetic route involves fermentation using a mutant of ''
E. coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
''.
Evonik (formerly Degussa) introduced a route from substituted
thiazolines.
Following this technology, -cysteine is produced by the hydrolysis of racemic 2-amino-Δ
2-thiazoline-4-carboxylic acid using ''Pseudomonas thiazolinophilum''.
Biosynthesis
In animals, biosynthesis begins with the amino acid
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
. The sulfur is derived from
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
, which is converted to
homocysteine through the intermediate
''S''-adenosylmethionine.
Cystathionine beta-synthase
Cystathionine-β-synthase, also known as CBS, is an enzyme () that in humans is encoded by the ''CBS'' gene. It catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine:
: L-serine + L-homocysteine \rightleft ...
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
In enzymology, a serine O-acetyltransferase () is an enzyme that catalyzes the chemical reaction
:acetyl-CoA + L-serine \rightleftharpoons CoA + ''O''-acetyl-L-serine
Thus, the two substrates of this enzyme are acetyl-CoA and L-serine, where ...
. The enzyme
cysteine synthase
In enzymology, a cysteine synthase () is an enzyme that catalyzes the chemical reaction
:''O''3-acetyl-L-serine + hydrogen sulfide \rightleftharpoons L-cysteine + acetate
Thus, the two substrates of this enzyme are ''O''3-acetyl-L-serine and h ...
, using sulfide sources, converts this ester into cysteine, releasing acetate.
Biological functions
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 functions.
Precursor to the antioxidant glutathione
Due to the ability of thiols to undergo redox reactions, cysteine and cysteinyl residues have
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
properties. Its antioxidant properties are typically expressed in the tripeptide
glutathione, which occurs in humans and 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 (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
. While glutamic acid is usually sufficient because amino acid nitrogen is recycled through glutamate as an intermediary, dietary cysteine and glycine supplementation can improve synthesis of glutathione.
Precursor to iron-sulfur clusters
Cysteine is an important source of
sulfide
Sulfide (British English also sulphide) is an inorganic anion of sulfur with the chemical formula S2− or a compound containing one or more S2− ions. Solutions of sulfide salts are corrosive. ''Sulfide'' also refers to chemical compounds lar ...
in human
metabolism. The sulfide in
iron-sulfur cluster
Iron–sulfur proteins (or iron–sulphur proteins in British spelling) are proteins characterized by the presence of iron–sulfur clusters containing sulfide-linked di-, tri-, and tetrairon centers in variable oxidation states. Iron–sulfur cl ...
s 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 protein
Copper proteins are proteins that contain one or more copper ions as prosthetic groups. Copper proteins are found in all forms of air-breathing life. These proteins are usually associated with electron-transfer with or without the involvement o ...
s, iron in
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
, and nickel in the
iFe hydrogenases. The sulfhydryl group also has a high
affinity
Affinity may refer to:
Commerce, finance and law
* Affinity (law), kinship by marriage
* Affinity analysis, a market research and business management technique
* Affinity Credit Union, a Saskatchewan-based credit union
* Affinity Equity Partn ...
for
heavy metals, so that proteins containing cysteine, such as
metallothionein
Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copp ...
, will
bind metals such as mercury, lead, and cadmium tightly.
Roles in protein structure
In the translation of messenger RNA molecules to produce polypeptides, cysteine is coded for by the UGU and UGC
codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s.
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 nonpolar 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 nonpolar amino acids such as
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
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
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO ...
.
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, which 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 noted below.
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
Sulfinic acids are oxoacids of sulfur with the structure RSO(OH). In these organosulfur compounds, sulfur is pyramidal.
Structure and properties
Sulfinic acids RSO2H are about 1000x more acidic than the corresponding carboxylic acid RCO2H. Su ...
and sulfonic acid
In organic chemistry, sulfonic acid (or sulphonic acid) refers to a member of the class of organosulfur compounds with the general formula , where R is an organic alkyl or aryl group and the group a sulfonyl hydroxide. As a substituent, it is kn ...
. 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
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
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
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
, which oxidizes 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 post-translational 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 caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...
s, 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.
Applications
Cysteine, mainly the -enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
, 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 flavors. -Cysteine is also used as a processing aid A processing aid is a substance used in the production of processed food, and which may end up in the finished product, but which is not, by law, required to be disclosed to the consumer as an ingredient.
Ethical concerns
NGOs, journalists, and f ...
for baking.
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
Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals.
The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...
's keratin.
Cysteine is a very popular target for site-directed labeling experiments to investigate biomolecular structure and dynamics. Maleimides selectively attach to cysteine using a covalent Michael addition. Site-directed spin labeling for EPR or paramagnetic relaxation-enhanced NMR also uses cysteine extensively.
Reducing toxic effects of alcohol
Cysteine has been proposed as a preventive or antidote for some of the negative effects of alcohol, including liver damage and hangover. It counteracts the poisonous effects of acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
. Cysteine supports the next step in metabolism, which turns acetaldehyde into acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
.
In a rat
Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...
study, test animals received an LD90 dose of acetaldehyde. Those that received cysteine had an 80% survival rate; when both cysteine and thiamine were administered, all animals survived. The control group
In the design of experiments, hypotheses are applied to experimental units in a treatment group.
In comparative experiments, members of a control group receive a standard treatment, a placebo, or no treatment at all. There may be more than one tr ...
had a 10% survival rate.
In 2020 an article was published that suggests L-cysteine might also work in humans.
''N''-Acetylcysteine
''N''-Acetyl--cysteine is a derivative of cysteine wherein an acetyl group
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...
is attached to the nitrogen atom. This compound is sold as a dietary supplement, and used as an antidote in cases of acetaminophen
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
overdose.
Sheep
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
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
sheep that can make their own cysteine have been developed.
Dietary restrictions
The animal-originating sources of -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, -cysteine can also be sourced from microbial or other synthetic processes.
See also
* Amino acids
* Cysteine metabolism
Cysteine metabolism refers to the biological pathways that consume or create cysteine. The pathways of different amino acids and other metabolites interweave and overlap to creating complex systems.cysteine is metabolism creating complex systems
...
* Cystinuria
* Saville reaction
* Sullivan reaction
Sullivan may refer to:
People
Characters
* Chloe Sullivan, from the television series ''Smallville''
* Colin Sullivan, a character in the film ''The Departed'', played by Matt Damon
* Harry Sullivan (''Doctor Who''), from the British science f ...
References
Further reading
*
External links
Cysteine MS Spectrum
International Kidney Stone Institute
* [https://web.archive.org/web/20080503021235/http://www.kolumbus.fi/justal/klami/ 952-10-3056-9 Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine]
Cystine Kidney Stones
Kosher View of L-Cysteine
{{Authority control
Proteinogenic amino acids
Glucogenic amino acids
Sulfur amino acids
Thiols
Food additives
E-number additives
Excitatory amino acids