Cysteine 52644 221736699 2008-06-25T21:28:09Z DOI bot 6652755 Citation maintenance. Added: doi_brokendate. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{distinguish|cystine}} {{ redirect-acronym|CYS|[[California Youth Symphony]]}} {{NatOrganicBox | image= [[Image:Cystein - Cysteine.svg|200px|Skeletal structure of <small>L</small>-cysteine]] <br>[[Image:L-cysteine-3D-balls2.png|100px|3D model of the amino acid cysteine]] [[Image:L-cysteine-3D-vdW2.png|100px|Space-filling model of the amino acid cysteine]] | name=(2R)-2-amino-3-sulfanyl-propanoic acid | PubChem=5862 | CAS = 52-90-4 | SMILES = N[C@@H](S)C(O)=O | C=3 | H=7 | N=1 | O=2 | S=1 | mass=121.16 g/mol }} '''Cysteine''' (abbreviated as '''Cys''' or '''C''')<ref>{{cite web | author=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature | title=Nomenclature and Symbolism for Amino Acids and Peptides | work=Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology etc | url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/ | accessdate=2007-05-17}}</ref> is an α-[[amino acid]] with the [[chemical formula]] HO<sub>2</sub>CCH(NH<sub>2</sub>)CH<sub>2</sub>SH. It is a non-[[Essential amino acid|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]]. ==Sources== ===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 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 ===Industrial sources=== :''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<!--This is the first instance of the term "L-cysteine" yet the "L" is not explained. It should be.--> may be purified in high yield is by [[hydrolysis]] of [[human hair]]. Other sources include feathers and pig bristles. {{Facts|date=February 2008}}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 (biochemistry)|fermentation]] for some years, L-cysteine was unavailable until 2001 when [[Germany|German]] company [[Wacker Chemie]] introduced a production route via fermentation (non-human, non-animal origin). ===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 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.<ref>Hell, R. 1997. "Molecular physiology of plant sulfur metabolism" Planta 202:138-148. PMID: 9202491</ref> ==Biological functions== The cysteine thiol group is [[nucleophile|nucleophilic]] and easily oxidized. The reactivity is enhanced when the thiol ionized, and cysteine residues in proteins have [[acid dissociation constant|pK<sub>a</sub>]] values close to neutrality, so are often in their reactive [[thiolate]] form in the cell.<ref>{{cite journal | author = Bulaj G, Kortemme T, Goldenberg D | title = Ionization-reactivity relationships for cysteine thiols in polypeptides. | journal = Biochemistry | volume = 37 | issue = 25 | pages = 8965–72 | year = 1998 | pmid = 9636038 | doi = 10.1021/bi973101r <!--Retrieved from CrossRef by DOI bot-->}}</ref> 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 (biochemistry)|substrate]]. ===Oxidation to cystine linkages=== Oxidation of cysteine produces the [[disulfide bond|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 Isomerase]]s 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 cluster]]s and in [[nitrogenase]] is extracted from cysteine, which is converted to [[alanine]] in the process.<ref>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.</ref> ===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 finger]]s and [[alcohol dehydrogenase]], copper in the [[plastocyanin|blue copper protein]]s, iron in [[cytochrome P450]], and nickel in the [NiFe]-[[hydrogenase]]s.<ref>S. J. Lippard, J. M. Berg “Principles of Bioinorganic Chemistry” University Science Books: Mill Valley, CA; 1994. ISBN 0-935702-73-3.</ref> The thiol group also has a high [[affinity]] for [[heavy metals]], so that proteins containing cysteine will [[ligand|bind]] metals such as mercury, lead, and cadmium tightly.<ref>{{cite journal | author = Baker D, Czarnecki-Maulden G | title = Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities. | journal = J Nutr | volume = 117 | issue = 6 | pages = 1003–10 | year = 1987 | pmid = 3298579 | doi = 10.1126/science.2237411.<br> | doi_brokendate = 2008-06-25}}</ref> ===Post-translational modifications=== Aside from its oxidation to cystine, cysteine participates in numerous [[Posttranslational modification]]s. 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. [[Intein]]s 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 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.{{Fact|date=June 2007}} L-cysteine is also used as a [[improving agent|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. [[Maleimide]]s 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.<ref name="http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm">[http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm http://quitsmoking.about.com/cs/nicotineinhaler/a/cigingredients.htm]</ref> 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== [[Image:Cystine-skeletal.png|thumb|right|150px|[[Cystine]], showing [[disulfide bond]]]] 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. ==Hangover remedy== Cysteine has been linked to aiding in the remedy of certain [[hangover]] symptoms. It directly counteracts the poisonous effects of [[acetaldehyde]]<ref name="http://www.lef.org/protocols/prtcl-004.shtml">[http://www.lef.org/protocols/prtcl-004.shtml http://www.lef.org/protocols/prtcl-004.shtml]</ref> , which is the major by-product of alcohol metabolism and is responsible for most of the harmful effects of drinking. Cysteine supports the next step in metabolism, which produces 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 which received cysteine had an 80% survival rate; when [[thiamine]] was added, all animals survived.<ref>Effects of cysteine on acetaldehyde lethality http://www.springerlink.com/content/w307w62037125v33/</ref> The actual effectiveness of consuming cysteine as part of a hangover remedy is unclear. ====N-acetylcysteine (NAC)==== [[N-acetylcysteine|N-acetyl-<small>L</small>-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 acid]]s * [[Thiol]]s * [[Cysteine metabolism]] * [[Cystinuria]] ==References== <references/> ==External links== * [http://www.compchemwiki.org/index.php?title=Cysteine Computational Chemistry Wiki] * [http://www.iksi.org International Kidney Stone Institute] * [http://www.chemie.fu-berlin.de/chemistry/bio/aminoacid/cystein_en.html http://www.chemie.fu-berlin.de/chemistry/bio/aminoacid/cystein en.html] * [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T36-3XB0N6H-H&_coverDate=09/10/1999&_alid=241945989&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4938&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=3cb10a335716303532fc517906a12b3a On the hydrophobic nature of cysteine.] * [http://urn.fi/URN:ISBN:952-10-3056-9 Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine] * [http://cystinuriaclearinghouse.com/index.html Cystine Kidney Stones] {{AminoAcids}} {{E number infobox 920-929}} [[Category:Proteinogenic amino acids]] [[Category:Glucogenic amino acids]] [[Category:Sulfur amino acids]] [[Category:Thiols]] [[ar:سيستيين]] [[ca:Cisteïna]] [[cs:Cystein]] [[de:Cystein]] [[es:Cisteína]] [[eo:Cisteino]] [[fr:Cystéine]] [[ko:시스테인]] [[id:Sistein]] [[it:Cisteina]] [[he:ציסטאין]] [[lv:Cisteīns]] [[lb:Cystein]] [[lt:Cisteinas]] [[hu:Cisztein]] [[nl:Cysteïne]] [[ja:システイン]] [[no:Cystein]] [[pl:Cysteina]] [[pt:Cisteína]] [[ru:Цистеин]] [[fi:Kysteiini]] [[sv:Cystein]] [[uk:Цистеїн]] [[zh:半胱氨酸]]