(Redirected from L-cysteine)
'Cysteine' is an α-
amino acid with the
chemical formula HO
2CCH(NH
2)CH
2SH. Its three letter code is cys, its one letter code is C, and its codons are UGU and UGC. It is not an
essential amino acid, which means that humans synthesise it. With a
thiol side chain, leucine is classified as a
hydrophobic 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.
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 then combines homocysteine and serine to form the unsymmetrical 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, releaseing acetate.
[1]
Biological functions
The cysteine thiol group is
nucleophilic and easily oxidized. The reactivity is enhanced when the thiol ionised, and cysteine residues in proteins have
pKa values close to neutrality, so are often in their reactive
thiolate form in the cell.
[2] 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 North American 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). Intracellularly, disulfide bridges between cysteine residues within a polypeptide support the protein's secondary structure.
Insulin is an example of a protein with cystine crosslinking, where 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 generally oxidized to cystine and no longer functions as a nucleophile.
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.
[3]
Metal ion binding
Beyond the iron-sulfur proteints, 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.
[4] 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.
[5]
Post translational modifications
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, which 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.
Dietary sources
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 content is relatively high in proteins found in eggs, meat, red peppers, garlic, onions, broccoli, brussel sprouts, oats, milk, whey protein, and wheat germ. However, it is not classified as an
essential amino acid, and 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. Conversely, cysteine 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.
Production
Currently 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 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 a
German company ("Wacker Chemie"?) introduced a production route via fermentation (non-human, non-animal origin.
Applications
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.
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 also uses cysteine extensively.
In a 1994 report released by five top
cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives.
[http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm] 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).
Sheep
Cysteine is required by
sheep in order to produce wool, however it is an essential amino-acid that must be taken in as food from grass. Consequently during drought conditions, sheep stop producing wool; however,
transgenic sheep have been developed which can make their own cysteine.
Hangover Remedy
Cysteine has been linked to aiding in the remedy of certain
hangover symptoms. It directly counteracts the poisonous effects of
acetaldehyde, a particularly toxic by-product of alcohol in the human body. Cysteine attracts the toxin, breaking it down into the non-toxic
acetate, a substance similar to vinegar. The actual effectiveness of consuming cysteine as part of a hangover remedy is unclear.
[http://www.lef.org/protocols/prtcl-004.shtml]
N-acetylcysteine (NAC)
N-acetyl-L-cysteine (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
acetominophen overdose.
See also
★
selenocysteine
★
amino acids
★
thiols
★
cysteine metabolism
★
cystinuria
References
1. Hell, R. 1997. "Molecular physiology of plant sulfur metabolism" Planta 202:138-148. PMID: 9202491
2. Ionization-reactivity relationships for cysteine thiols in polypeptides., Bulaj G, Kortemme T, Goldenberg D, , , Biochemistry, 1998
3. Roland Lill, Ulrich Mühlenhoff “Iron-Sulfur Protein Biogenesis in Eukaryotes: Components and Mechanisms” Annual Review of Cell and Developmental Biology, 2006, Volume 22, pp. 457-486. doi:10.1146/annurev.cellbio.22.010305.104538.
4. S. J. Lippard, J. M. Berg “Principles of Bioinorganic Chemistry” University Science Books: Mill Valley, CA; 1994. ISBN 0-935702-73-3.
5. Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities., Baker D, Czarnecki-Maulden G, , , J Nutr, 1987
External links
★
Computational Chemistry Wiki
★
International Kidney Stone Institute
★
http://www.chemie.fu-berlin.de/chemistry/bio/aminoacid/cystein en.html
★
On the hydrophobic nature of cysteine.
★
Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine
★
Cystine Kidney Stones
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