- Not to be confused with cystine, its oxidized dimer.
(abbreviated as Cys
) is an α-amino acid
with the chemical formula
SH. It is a non-essential
amino acid, which means that humans can synthesize it. Its codons
are UGU and UGC. With a thiol
side chain, cysteine is classified as a hydrophilic
amino acid. Because of the high reactivity of this thiol, cysteine is an important structural and functional component of many proteins and enzymes. Cysteine is named after cystine
, its oxidized dimer
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 syndromes
. Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine
is available. Cysteine is potentially toxic and is catabolized
in the gastrointestinal tract and blood plasma. In contrast, cysteine is absorbed during digestion as cystine
, which is more stable in the gastrointestinal tract. 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: pork, sausage meat, chicken, turkey, duck, luncheon meat
- Animal vegetarian sources: eggs, milk, whey protein, ricotta, cottage cheese, yogurt
- Vegan sources: red peppers, garlic, onions, broccoli, brussels sprouts, oats, granola, wheat germ
- See also Food safety in China#Soy sauce made from human hair.
At the present time, the cheapest source of material from which food-grade L-cysteine may be purified in high yield is by hydrolysis
of human hair
. Other sources include feathers and pig bristles. The companies producing cysteine by hydrolysis are located mainly in China
. There is some debate as to whether or not consuming L-cysteine derived from human hair constitutes cannibalism
. Although many other amino acids were accessible via fermentation
for some years, L-cysteine was unavailable until 2001 when German
company Wacker Chemie
introduced a production route via fermentation (non-human, non-animal origin).
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
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 bacteria
, cysteine biosynthesis again 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 thiol group is nucleophilic
and easily oxidized. The reactivity is enhanced when the thiol 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 thiol group of cysteine has numerous biological functions.
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
Oxidation to cystine linkages
Oxidation of cysteine produces the disulfide
cystine. 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 protein stability in the harsh extracellular environment, 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 secondary 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 no longer functional as a nucleophiles.
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 thiol group also has a high affinity
for heavy metals
, so that proteins containing cysteine will bind
metals such as mercury, lead, and cadmium tightly.
Aside from its oxidation to cystine, cysteine participates in numerous Posttranslational modifications
. The nucleophilic
thiol 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 flavors. L-cysteine is also used as a processing aid
for baking. Small quantities (in the tens of ppm range) help to soften the dough and thus reduce processing time. http://www.cfsan.fda.gov/~dms/foodic.html
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 Michael addition. 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; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).
Cysteine is required by sheep in order to produce wool: it is an essential amino acid which must be taken in as food from grass. As a consequence, during drought conditions, sheep stop producing wool; however, transgenic sheep which can make their own cysteine have been developed.
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
, which is the major by-product of alcohol metabolism and is responsible for most of the negative aftereffects and long-term damage associated with alcohol use (but not the immediate effects of drunkenness
). Cysteine supports the next step in metabolism, which turns acetaldehyde into the relatively harmless acetic acid
. In a rat
study, test animals received a LD50
dose of acetaldehyde (the amount which normally kills half of all animals). Those that received cysteine had an 80% survival rate; when thiamine
was added, all animals survived. There is not yet direct evidence for or against its effectiveness in humans who consume alcohol at normal levels.
(NAC) is a derivative of cysteine wherein an acetyl group
is attached to the nitrogen atom. This compound is sometimes considered as a dietary supplement, although it is not an ideal source since it is catabolized in the gut. NAC is often used as a cough medicine because it breaks up the disulfide bonds in the mucus
and thus liquefies it, making it easier to cough up. NAC is also used as a dietary supplement as already indicated above, as well as a specific antidote
in cases of acetaminophen