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Cysteine (symbol Cys or C; ) is a semiessential
proteinogenic amino acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino ac ...
with the formula . The
thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a
deprotonated Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.edu ...
catalytic
residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applie ...
, 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 In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
derivative
cystine Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
, 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 E920. Cysteine is
encoded In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
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 p ...
s UGU and UGC. The sulfur-containing amino acids cysteine and methionine 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 i ...
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.


Dietary sources

Cysteinyl is a residue in high- protein foods. Although classified as a non
essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...
, 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 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 and Muslim halal laws, is also available, albeit at a higher price. The synthetic route involves fermentation using a mutant of '' E. coli''.
Evonik Evonik Industries AG is a stock-listed German specialty chemicals company headquartered in Essen, North Rhine-Westphalia, Germany. It is the second largest chemicals company in Germany, and one of the largest specialty chemicals companies in the ...
(formerly Degussa) introduced a route from substituted
thiazoline Thiazolines (or dihydrothiazoles) are a group of isomeric 5-membered heterocyclic compounds containing both sulfur and nitrogen in the ring. Although unsubstituted thiazolines are rarely encountered themselves, their derivatives are more common ...
s. Following this technology, -cysteine is produced by the hydrolysis of racemic 2-amino-Δ2-thiazoline-4-carboxylic acid using ''Pseudomonas thiazolinophilum''.


Biosynthesis

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.
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 Cystathionine is an intermediate in the synthesis of cysteine. Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
. The enzyme
cystathionine gamma-lyase The enzyme cystathionine γ-lyase (EC 4.4.1.1, CTH or CSE; also cystathionase; systematic name L-cystathionine cysteine-lyase (deaminating; 2-oxobutanoate-forming)) breaks down cystathionine into cysteine, 2-oxobutanoate ( α-ketobutyrate), and ...
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
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 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 ...
and easily oxidized. The reactivity is enhanced when the thiol is ionized, and cysteine
residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applie ...
s in proteins have pKa values close to neutrality, so are often in their reactive
thiolate In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
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 lubricants, ...
properties. Its antioxidant properties are typically expressed in the tripeptide
glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, per ...
, 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 Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogen ...
, 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 syn ...
. 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 clusters and in nitrogenase is extracted from cysteine, which is converted to
alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...
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 Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH ...
, 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 superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various comp ...
, 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 Par ...
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, cop ...
, will
bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative n ...
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 p ...
s. Cysteine has traditionally been considered to be a
hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are no ...
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 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 Hydrophobicity scales are values that define the relative hydrophobicity or hydrophilicity of amino acid residues. The more positive the value, the more hydrophobic are the amino acids located in that region of the protein. These scales are common ...
, 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 bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s, 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 environment A reducing atmosphere is an atmospheric condition in which oxidation is prevented by removal of oxygen and other oxidizing gases or vapours, and which may contain actively reducing gases such as hydrogen, carbon monoxide, and gases such as hydro ...
s, disulfide bonds are generally unstable in the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrio ...
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. Sul ...
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 isomerase Protein disulfide isomerase (), or PDI, is an enzyme in the endoplasmic reticulum (ER) in eukaryotes and the periplasm of bacteria that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they ...
s catalyze the proper formation of
disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s; the cell transfers
dehydroascorbic acid Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and othe ...
to the 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 modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosom ...
s. The
nucleophilic 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 ...
sulfhydryl group allows cysteine to conjugate to other groups, e.g., in
prenylation Prenylation (also known as isoprenylation or lipidation) is the addition of hydrophobic molecules to a protein or a biomolecule. It is usually assumed that prenyl groups (3-methylbut-2-en-1-yl) facilitate attachment to cell membranes, similar ...
. 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 The Maillard reaction ( ; ) is a chemical reaction between amino acids and reducing sugars that gives browned food its distinctive flavor. Seared steaks, fried dumplings, cookies and other kinds of biscuits, breads, toasted marshmallows, and ma ...
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's keratin. Cysteine is a very popular target for site-directed labeling experiments to investigate biomolecular structure and dynamics.
Maleimide Maleimide is a chemical compound with the formula H2C2(CO)2NH (see diagram). This unsaturated imide is an important building block in organic synthesis. The name is a contraction of maleic acid and imide, the -C(O)NHC(O)- functional group. Malei ...
s selectively attach to cysteine using a covalent Michael addition.
Site-directed spin labeling Site-directed spin labeling (SDSL) is a technique for investigating the structure and local dynamics of proteins using electron spin resonance. The theory of SDSL is based on the specific reaction of spin labels with amino acids. A spin label's bu ...
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 m ...
. 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 study, test animals received an LD90 dose of acetaldehyde. Those that received cysteine had an 80% survival rate; when both cysteine and
thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...
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 An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...
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 acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s *
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 Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduria. ...
*
Saville reaction The Saville reaction is a chemical reaction in which mercury replaces a nitrosyl from a thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic subs ...
*
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