Cystine is the oxidized derivative of the amino acid cysteine and has the chemical formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mechanical linkage that allows proteins to retain their three-dimensional structure.[Nelson, D. L.; Cox, M. M. (2000) Lehninger, Principles of Biochemistry. 3rd Ed. Worth Publishing: New York. .]
Formation and reactions
Structure
Cystine is the
disulfide derived from the amino acid
cysteine. The conversion can be viewed as an oxidation:
Cystine contains a
disulfide bond, two amine groups, and two carboxylic acid groups. As for other amino acids, the amine and carboxylic acid groups exist in rapid equilibrium with the ammonium-carboxylate
tautomer. The great majority of the literature concerns the
l,l-cystine, derived from
l-cysteine. Other isomers include
d,d-cystine and the
meso isomer d,l-cystine, neither of which is biologically significant.
Occurrence
Cystine is common in many foods such as eggs, meat, dairy products, and whole grains as well as skin, horns and hair. It was not recognized as being derived of
proteins until it was isolated from the horn of a
cow in 1899.
[ "cystine". Encyclopædia Britannica. 2007. Encyclopædia Britannica Online. 27 July 2007] Human hair and skin contain approximately 10–14% cystine by mass.
History
Cystine was discovered in 1810 by the English chemist William Hyde Wollaston, who called it "cystic oxide".
[ On p. 227, Wollaston named cystine "cystic oxide".] In 1833, the Swedish chemist Jöns Jacob Berzelius named the amino acid "cystine".
[ From p. 424: "10. Cystine. Cette substance a été découverte dans les calculs urinaires par Wollaston, … je me suis donc permis de changer le nom qu'avait proposé cet homme distingué." (10. Cystine. This substance was discovered in urinary calculi by Wollaston, who gave it the name of "cystic oxide" because it dissolves as much in acids as in alkalis, and it resembles, in this respect, some metallic oxides; but, in a way, the reason that alleged to justify it is not valid: I have therefore taken the liberty of changing the name that this distinguished man had proposed.)] The Norwegian chemist Christian J. Thaulow determined, in 1838, the empirical formula of cystine.
In 1884, the 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
cysteine.
[ 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 .] In 1899, cystine was first isolated from protein (horn tissue) by the Swedish chemist Karl A. H. Mörner (1855-1917).
The chemical structure of cystine was determined by synthesis in 1903 by the German chemist
Emil Erlenmeyer.
[ Discussion of the synthesis of cystine begins on p. 241.][Erlenmeyer's findings regarding the structure of cystine were confirmed in 1908 by Fischer and Raske. See: ]
The history of cystine and cysteine is complicated by the dimer-monomer relationship of the two.
The sulfur within the structure of cysteine and cystine has been subject of historical interest.
Redox
It is formed from the oxidation of two cysteine molecules, which results in the formation of a
disulfide bond. In cell biology, cystine residues (found in proteins) only exist in non-reductive (oxidative) organelles, such as the secretory pathway (endoplasmic reticulum,
Golgi apparatus,
, and vesicles) and extracellular spaces (e.g., extracellular matrix). Under reductive conditions (in the cytoplasm, nucleus, etc.) cysteine is predominant. The disulfide link is readily reduced to give the corresponding
thiol cysteine. Typical thiols for this reaction are
mercaptoethanol and
dithiothreitol:
- (SCH2CH(NH2)CO2H)2 + 2 RSH → 2 HSCH2CH(NH2)CO2H + RSSR
Because of the facility of the thiol-disulfide exchange, the nutritional benefits and sources of cystine are identical to those for the more-common
cysteine. Disulfide bonds cleave more rapidly at higher temperatures.
Cystine-based disorders
The presence of cystine in urine is often indicative of amino acid reabsorption defects.
Cystinuria has been reported to occur in dogs.
In humans the excretion of high levels of cystine crystals can be indicative of
cystinosis, a rare genetic disease. Cystine stones account for about 1-2% of kidney stone disease in adults.
Various derivatives of cysteamine are used to address cystinosis.
Biological transport
Cystine serves as a substrate for the cystine-glutamate antiporter. This transport system, which is highly specific for cystine and glutamate, increases the concentration of cystine inside the cell. In this system, the anionic form of cystine is transported in exchange for glutamate. Cystine is quickly reduced to cysteine. Cysteine prodrugs, e.g.
acetylcysteine, induce release of glutamate into the extracellular space.
See also
External links
