Editing Cysteine (section)

==Biological functions==
The cysteine sulfhydryl group is [[nucleophile|nucleophilic]] and easily oxidized. The reactivity is enhanced when the thiol is ionized, and cysteine [[amino acid residue|residue]]s 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 |vauthors=Bulaj G, Kortemme T, Goldenberg DP |title=Ionization-reactivity relationships for cysteine thiols in polypeptides |journal=Biochemistry |volume=37 |issue=25 |pages=8965–72 |date=June 1998 |pmid=9636038 |doi=10.1021/bi973101r}}</ref> 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]] 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]]. 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.<ref>{{cite journal |last1=Sekhar |first1=Rajagopal V |last2=Patel |first2=Sanjeet G |title=Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation |journal=The American Journal of Clinical Nutrition |date=2011 |volume=94 |issue=3 |pages=847–853 |doi=10.3945/ajcn.110.003483 |pmid=21795440 |url= |pmc=3155927 }} {{Open Access}}</ref>

===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>{{cite journal |vauthors=Lill R, Mühlenhoff U |title=Iron-sulfur protein biogenesis in eukaryotes: components and mechanisms |journal=Annu. Rev. Cell Dev. Biol. |volume=22 |pages=457–86 |year=2006 |pmid=16824008 |doi=10.1146/annurev.cellbio.22.010305.104538|url=http://nbn-resolving.de/urn:nbn:de:bvb:12-bsb00055966-1 }}</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>{{cite book |first1=Stephen J. |last1=Lippard |first2=Jeremy M. |last2=Berg |title=Principles of Bioinorganic Chemistry |publisher=University Science Books |location=Mill Valley, CA |year=1994 |isbn=978-0-935702-73-6}}{{page needed|date=July 2013}}</ref> The sulfhydryl group also has a high [[Affinity (pharmacology)|affinity]] for [[Heavy metal (chemistry)|heavy metal]]s, so that proteins containing cysteine, such as [[metallothionein]], will [[ligand|bind]] metals such as mercury, lead, and cadmium tightly.<ref>{{cite journal |vauthors=Baker DH, Czarnecki-Maulden GL |title=Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities |journal=J. Nutr. |volume=117 |issue=6 |pages=1003–10 |date=June 1987 |pmid=3298579 |doi=10.1093/jn/117.6.1003 |doi-access=free }}</ref>

===Roles in protein structure===
In the translation of messenger RNA molecules to produce polypeptides, cysteine is coded for by the UGU and UGC [[codon]]s.

Cysteine has traditionally been considered to be a [[hydrophilic]] amino acid, based largely on the chemical parallel between its [[thiol group|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.<ref>{{cite journal |author=Heitmann P |title=A model for sulfhydryl groups in proteins. Hydrophobic interactions of the cystein side chain in micelles |journal=Eur. J. Biochem. |volume=3 |issue=3 |pages=346–50 |date=January 1968 |pmid=5650851 |doi=10.1111/j.1432-1033.1968.tb19535.x|doi-access=free }}</ref> In a statistical analysis of the frequency with which amino acids appear in various proteins, 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<ref>{{cite web|url=http://wbiomed.curtin.edu.au/biochem/tutorials/AAs/AA.html|title=A Review of Amino Acids (tutorial)|publisher=Curtin University|access-date=2015-09-09|archive-url=https://web.archive.org/web/20150907052410/http://wbiomed.curtin.edu.au/biochem/tutorials/AAs/AA.html|archive-date=2015-09-07|url-status=dead}}</ref>), those of which were much greater than that of known polar amino acids such as serine and [[threonine]].<ref>{{cite journal |vauthors=Nagano N, Ota M, Nishikawa K |title=Strong hydrophobic nature of cysteine residues in proteins |journal=FEBS Lett. |volume=458 |issue=1 |pages=69–71 |date=September 1999 |pmid=10518936 |doi=10.1016/S0014-5793(99)01122-9|s2cid=34980474 |doi-access=free |bibcode=1999FEBSL.458...69N }}</ref> [[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,<ref>{{cite web | url = http://www.russelllab.org/aas/hydrophobic.html | title = Hydrophobic amino acids | access-date = 2012-09-16 | last1 = Betts | first1 = M.J. |author2=R.B. Russell | year = 2003 | work = Amino Acid Properties and Consequences of Substitutions, In: Bioinformatics for Geneticists | publisher = Wiley}}</ref><ref>{{cite web |url=http://webhost.bridgew.edu/fgorga/proteins/nonpolar.htm |title=Introduction to Protein Structure--Non-Polar Amino Acids |access-date=2012-09-16 |last1=Gorga |first1=Frank R. |date=1998–2001 |url-status=dead |archive-url=https://web.archive.org/web/20120905162400/http://webhost.bridgew.edu/fgorga/proteins/nonpolar.htm |archive-date=2012-09-05 }}</ref> though it is sometimes also classified as slightly polar,<ref>{{cite web | url = http://www.elmhurst.edu/~chm/vchembook/561aminostructure.html | title = Virtual Chembook--Amino Acid Structure | access-date = 2012-09-16 | publisher = Elmhurst College | url-status = dead | archive-url = https://web.archive.org/web/20121002050150/http://www.elmhurst.edu/~chm/vchembook/561aminostructure.html | archive-date = 2012-10-02 }}</ref> or polar.<ref name=microbial/>

Most cysteine residues are covalently bonded to other cysteine residues to form [[disulfide bond]]s, which play an important role in the folding and stability of some proteins, usually proteins secreted to the extracellular medium.<ref name=Sevier>{{cite journal |vauthors=Sevier CS, Kaiser CA |title=Formation and transfer of disulphide bonds in living cells |journal=Nat. Rev. Mol. Cell Biol. |volume=3 |issue=11 |pages=836–47 |date=November 2002 |pmid=12415301 |doi=10.1038/nrm954|s2cid=2885059 |doi-access=free }}</ref> Since most cellular compartments are [[reducing environment]]s, disulfide bonds are generally unstable in the [[cytosol]] with some exceptions as noted below.

[[Image:Cystine-skeletal.png|thumb|right|150px|Figure 2: [[Cystine]] (shown here in its neutral form), two cysteines bound together by a disulfide bond]]

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]] 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]]s catalyze the proper formation of [[disulfide bond]]s; the cell transfers [[dehydroascorbic acid]] 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]]s. The [[nucleophilic]] sulfhydryl group allows cysteine to conjugate to other groups, e.g., in [[prenylation]]. [[Ubiquitin]] [[ligase]]s transfer ubiquitin to its pendant, proteins, and [[caspase]]s, 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.