Cysteine
Cysteine is a semiessential proteinogenic amino acid with the formula HO2CCHCH2SH. The thiol side chain in cysteine often participates in enzymatic reactions, as a nucleophile. The thiol is susceptible to oxidation to give the disulfide derivative cystine, which serves an important structural role in many proteins. When used as a food additive, it has the E number E920. It is encoded by the codons UGU and UGC.
Cysteine has the same structure as serine, but with one of its oxygen atoms replaced by sulfur; replacing it with selenium gives selenocysteine. Like other natural proteinogenic amino acids, cysteine has chirality 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 have R chirality, because of the presence of sulfur as a second neighbour to the asymmetric carbon. The remaining chiral amino acids, having lighter atoms in that position, have S chirality.
Dietary sources
Like other common amino acids, cysteine is found in high-protein foods. Although classified as a nonessential amino acid, 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.Like other amino acids, in its monomeric "free" form cysteine has an amphoteric character.
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 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. Degussa introduced a route from substituted thiazolines. 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 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 plants and bacteria, cysteine biosynthesis also starts from serine, which is converted to O-acetylserine by the enzyme serine transacetylase. The enzyme cysteine synthase, using sulfide sources, converts this ester into cysteine, releasing acetate.Biological functions
The cysteine sulfhydryl group is nucleophilic and easily oxidized. The reactivity is enhanced when the thiol is 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 sulfhydryl group of cysteine has numerous biological functions, and cysteine may have played an important role in the development of primitive life on Earth.Precursor to the antioxidant glutathione
Due to the ability of thiols to undergo redox reactions, cysteine has 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 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.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 -hydrogenases. The sulfhydryl group also has a high affinity for heavy metals, so that proteins containing cysteine, such as metallothionein, will bind 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 codons.Cysteine has traditionally been considered to be a hydrophilic 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, those of which were much greater than that of known polar amino acids such as serine and threonine. 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, 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 bonds, 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 environments, disulfide bonds are generally unstable in the cytosol with some exceptions as noted below.
, 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. 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 isomerases catalyze the proper formation of disulfide bonds; 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 modifications. The nucleophilic sulfhydryl 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.
Applications
Cysteine, mainly the -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. -Cysteine is also used as a processing aid 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. Maleimides selectively attach to cysteine using a covalent Michael addition. Site-directed spin labeling for EPR or paramagnetic relaxation-enhanced NMR also uses cysteine extensively.