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Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the chemical formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. Cysteine is chiral, but both D and L-cysteine are found in nature. LCysteine is a protein monomer in all biota, and D-cysteine acts as a signaling molecule in mammalian nervous systems. Cysteine is named after its discovery in urine, which comes from the urinary bladder or cyst, from Greek language κύστη kýsti, "bladder".
The thiol is susceptible to oxidation to give the disulfide bond derivative cystine, which serves an important structural role in many . In this case, the symbol Cyx is sometimes used. The deprotonated form can generally be described by the symbol Cym as well.
When used as a food additive, cysteine has the E number E920.
Cysteine is Genetic code by the UGU and UGC.
Some animal-originating sources of -cysteine as a food additive contravene kosher, halal, vegan, or vegetarian diets.See, e.g., Rabbi Blech does not address hog hair-derived cysteine, which is almost certainly treyf. To avoid this problem, synthetic -cysteine, compliant with Jewish kosher and Muslim halal laws, is also available, albeit at a higher price. The typical synthetic route involves fermentation with an artificial Escherichia coli strain.
Alternatively, Evonik (formerly Degussa) introduced a route from substituted . Pseudomonas thiazolinophilum hydrolyzes racemic 2amino-Δ2thiazoline-4carboxylic acid to cysteine.
Cysteine has traditionally been considered to be a hydrophilic amino acid, based largely on the chemical parallel between its thiol 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 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), 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.
Most cysteine residues are covalently bonded to other cysteine residues to form , 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.
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 isomerases catalyze the proper formation of ; 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 transfer ubiquitin to its pendant, proteins, and , which engage in proteolysis in the apoptotic cycle. 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.
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. 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 rat study, test animals received an Lethal dose dose of acetaldehyde. Those that received cysteine had an 80% survival rate; when both cysteine and thiamine were administered, all animals survived. The control group had a 10% survival rate.
In 2020 an article was published that suggests L-cysteine might also work in humans.
(2024). 9783527306732 ISBN 9783527306732
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 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 nucleophile 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.
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.
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 and alcohol dehydrogenase, copper in the plastocyanin, iron in cytochrome P450, and nickel in the NiFe-. (1994). 9780935702736, University Science Books. ISBN 9780935702736 The sulfhydryl group also has a high affinity for heavy metals, so that proteins containing cysteine, such as metallothionein, will ligand 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 .
Evolutionary role of cysteine
Cysteine is considered a "newcomer" amino acid, being the 17th amino acid incorporated into the genetic code. Similar to other later-added amino acids such as methionine, tyrosine, and tryptophan, cysteine exhibits strong nucleophilic and redox-active properties. These properties contribute to the depletion of cysteine from respiratory chain complexes, such as Complexes I and Complex IV, since reactive oxygen species (ROS) produced by the respiratory chain can react with the cysteine residues in these complexes, leading to dysfunctional proteins and potentially contributing to aging. The primary response of a protein to ROS is the oxidation of cysteine and the loss of free thiol groups, resulting in increased Thiyl radical and associated protein cross-linking. In contrast, another sulfur-containing, redox-active amino acid, methionine, does not exhibit these biochemical properties and its content is relatively upregulated in Mitochondrion encoded proteins.
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 improving agent for baking.
Reducing toxic effects of alcohol
Cysteine has been proposed as a preventive or antidote for some of the negative effects of alcohol, including liver damage and hangover. It counteracts the poisonous effects of acetaldehyde. It binds to acetaldehyde to form the low-toxicity heterocycle methylthioproline.
N-Acetylcysteine
N-Acetylcysteine is a derivative of cysteine wherein an acetyl group is attached to the nitrogen atom. This compound is sold as a dietary supplement, and used as an antidote in cases of acetaminophen overdose.
Sheep
Cysteine is required by sheep to produce wool. It is an essential amino acid that is taken in from their feed. As a consequence, during drought conditions, sheep produce less wool; however, transgenic sheep that can make their own cysteine have been developed.
Chemical reactions
Being multifunctional, cysteine undergoes a variety of reactions. Much attention has focused on protecting the sulfhydryl group. Methylation of cysteine gives S-Methylcysteine. Treatment with formaldehyde gives the thiazolidine thioproline. Cysteine forms a variety of coordination complexes upon treatment with metal ions.
Safety
Relative to most other amino acids, cysteine is much more toxic. (1987). 9780121820435 ISBN 9780121820435
History
In 1884 German chemist Eugen Baumann found that when cystine was treated with a reducing agent, cystine revealed itself to be a dimer of a monomer which he named "cysteïne". From pp. 301-302: "Die Analyse der Substanz ergibt Werthe, welche den vom Cystin (C6H12N2S2O4) verlangten sich nähern, … nenne ich dieses Reduktionsprodukt des Cystins: Cysteïn." (Analysis of the substance cysteine reveals values which approximate those that required by cystine (C6H12N2S2O4), however the new base cysteine can clearly be recognized as a reduction product of cystine, to which the empirical formula C3H7NSO2, which previously been ascribed to cystine, is now ascribed. In order to indicate the relationships of this substance to cystine, I name this reduction product of cystine: "cysteïne".) Note: Baumann's proposed structures for cysteine and cystine (see p.302) are incorrect: for cysteine, he proposed CH3CNH2(SH)COOH .
See also
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