CYSTINE

L-CYSTINE

CAS number: 56-89-3
EC number: 200-296-3
Hill Formula: C₆H₁₂N₂O₄S₂
Molar Mass: 240.30 g/mol

Cystine is the oxidized dimer form of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. 
Cystine is a white solid that is slightly soluble in water. 
Cystine serves two biological functions: a site of redox reactions and a mechanical linkage that allows proteins to retain their three-dimensional structure.

Cystine, a crystalline, sulfur-containing amino acid that is formed from two molecules of the amino acid cysteine. 
Cystine can be converted to cysteine by reduction (in this case, the addition of hydrogen). 

Discovered in 1810, cystine was not recognized as a component of proteins until 1899, when Cystine was isolated from animal horn. 
Cystine is particularly abundant in skeletal and connective tissues and in hair, horn, and wool.

Cystine is considered one of the most convenient targets for protein modification. 
The sulfhydryl side chain of cysteine is considered an active nucleophilic moiety. 

Generally speaking, cystines are some of the lowest abundant surface-exposed amino acids. 
Cysteine is a more nucleophilic moiety in comparison to the primary amines, and this allows selective modifications of cystines over lysines. 

However, surface-exposed cysteines are rarely present on the exterior of the proteins, as they embed their side chain within the hydrophobic region of the protein. 
For example, once cysteines are on the surface of exposed proteins, this contributes to the forming of disulfide associations and ultimately to protein aggregation (agglomeration). 

This scheme is vital for protein stabilization. 
Maleimide chemistries are some of the most common approaches to labeling the side chain of cysteine, as they selectively react with the thiol group. 

The maleimide reaction is stable under physiological conditions, while lysines fail to react and the same reaction conditions. 
Thiols are recognized in oxidative terms to create disulfide ties. 

This oxidative reaction is involved in the cystine-cystine equilibrium, which is pivotal in the configuration of the 3D structure of the proteins, as the reaction conditions are very mild and do not affect the structural stability. 
The reaction is reversible and can be achieved through the addition of mercaptoethanol or dithiothreitol to decouple the disulfide bond.

In 1935, keratin was one of the earliest proteins to be modified; the surface-exposed cysteine was modified with iodoacetamide as reaction reagent.

Furthermore, terminal cysteines of papain, a proteolytic enzyme, were modified by Clark and Lowe using an α-bromoacetophenone reagent to alkylate cystines, which in turn were reduced to glycine and serine. 
The same approach of α-bromoacetophenone was used for the conjugation of flavin to the accessible cystine of papain. 

Several colorimetric procedures have been reported in the literature for estimating the number of thiol groups in any protein. 
This is due to the ease of oxidation of the sulfhydryl side chain using, for example, 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB), commonly referred to as Ellman's reagent. 
The colored thionitrobenzoate anion was released as each thiol group reacted with DTNB and was measured spectrophotometrically at λ412 nm with ɛ = 1.36 × 104 M− 1 cm− 1 at pH 8.

The ability to conjugate molecules of interest to the native cysteine through the formation of sulfur-sulfur bonds can be exploited to engineer new functionalities.
Some of the significant chemistries that have been reported in the literature are the use of an aminomethylation reaction, iodoacetamide, and maleimides.

A crystalline amino acid C6H12N2O4S2 that is widespread in proteins (such as keratins) and is a major metabolic sulfur source.

Cystine an amino acid that is particularly notable because Cystine is the least soluble of all of the naturally occurring amino acids and because Cystine precipitates out of solution in the genetic disease cystinuria to form stones in the urinary tract. 
Cystine is the chief sulfur-containing compound in protein. 

Cystine is generated by the union of two cysteine molecules and so is sometimes called dicysteine. 
Cystine is abbreviated Cys-Cys.

A crystalline amino acid, C6H12O4N2S2, occurring in most proteins, especially the keratins in hair, wool, and horn, and yielding cysteine on reduction.
Cystine is an oxidated derivative of the amino acid cysteine found in various nutritional products, acne treatments, and creams to treat cervical injury or inflammation.

L-Cystine is the stable, oxidized form of L-Cysteine. 
Cystine is known as a disulfide amino acid because Cystine consists of two Cysteine segments with their respective sulfur atoms bonded firmly together. 

The body can convert L-Cysteine to L-Cystine and vice versa, however L-Cysteine is the more bio-active of the two.
L-Cystine has a bland taste and can be taken in powder or capsule form. 

The powder is water soluble and weighs about 4.6 grams per level measuring teaspoon. 
An adequate supply of Vitamin C and B6 should always accompany any Cysteine or Cystine supplementation.

Cystine is an oxidized dimeric form of cysteine. 
Cystine is formed by linking two cysteine residues via a disulfide bond (Cys-S-S-Cys) between the -SH groups. 

Cystine is found in high concentrations in digestive enzymes and in the cells of the immune system, skeletal and connective tissues, skin, and hair. 
Hair and skin are 10-14% cystine. 

Cystine is the preferred form of cysteine for the synthesis of glutathione in cells involved in the immune system (e.g. macrophages and astrocytes). 
Lymphocytes and neurons prefer cysteine for glutathione production. Optimizing glutathione levels in macrophages and astrocytes with cystine allows these cells to provide cysteine to lymphocytes and neurons directly upon demand.

Pharmacodynamics of Cystine:
L-Cystine is a covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. 
Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the kidney. 

The compound produced when two cysteine molecules linked by a disulfide (S-S) bond. 
Cystine is required for proper vitamin B6 utilization and is also helpful in the healing of burns and wounds, breaking down mucus deposits in illnesses such as bronchitis as well as cystic fibrosis. 

Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches. 
Cystine increases the level of glutathione in the lungs, liver, kidneys and bone marrow, and this may have an anti-aging effect on the body by reducing age-spots etc.

Indication of Cystine:
Cystine has been claimed that L-cysteine has anti-inflammatory properties, that Cystine can protect against various toxins, and that Cystine might be helpful in osteoarthritis and rheumatoid arthritis. 
More research will have to be done before L-cysteine can be indicated for any of these conditions. 
Research to date has mostly been in animal models.

Mechanism of action of Cystine:
Certain conditions, e.g. an acetaminophen overdose, deplete hepatic glutathione and subject the tissues to oxidative stress resulting in loss of cellular integrity. 
L-Cystine serves as a major precursor for synthesis of glutathione.

Uses of Cystine:
As a non-essential amino acid.
Cystine is used as a flavoring, dough strengthener and nutritional supplement in foods.

Antistatic
Antistatic agent
Fragrance ingredient
Hair conditioning    
Hair conditioning agent
Personal care - hair styling and care - hair conditioner - leave-in    Leave-in everyday hair conditioners and detanglers
Masking    
Softener and conditioner

Formation and reactions of Cystine:
Cystine is common in many foods such as eggs, meat, dairy products, and whole grains as well as skin, horns and hair. 
Cystine was not recognized as being derived of proteins until Cystine was isolated from the horn of a cow in 1899.

Human hair and skin contain approximately 10–14% cystine by mass.
Cystine was discovered in 1810 by William Hyde Wollaston.

Redox:
Cystine 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, lysosomes, 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.

Biological transport of Cystine:
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.

Cystine hair nutritional supplements:
Cysteine supplements are sometimes marketed as anti-aging products with claims of improved skin elasticity.
Cysteine is more easily absorbed by the body than cystine, so most supplements contain cysteine rather than cystine. 
N-acetyl-cysteine (NAC) is better absorbed than other cysteine or cystine supplements.

Storage and Shipping Information of Cystine:
Ship Code: Ambient Temperature Only
Toxicity: Standard Handling
Storage: +15°C to +30°C
Do not freeze: Ok to freeze
Special Instructions: Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Physicochemical Information of Cystine:
Density: 1.66 g/cm3 (20 °C)
Melting Point: 261 - 262 °C (decomposition)
Bulk density: 300 kg/m3
Solubility: 0.19 g/l insoluble

Identifiers of Cystine:
CAS Number: 56-89-3
ChEBI: CHEBI:35492
ChEMBL: ChEMBL366563
ChemSpider: 575
ECHA InfoCard: 100.000.270
IUPHAR/BPS: 5413
KEGG: C01420
PubChem CID: 67678
UNII: 48TCX9A1VT
CompTox Dashboard (EPA): DTXSID2046418
InChI:
InChI=1S/C6H12N2O4S2/c7-3(5(9)10)1-13-14-2-4(8)6(11)12/h3-4H,1-2,7-8H2,(H,9,10)(H,11,12) check
Key: LEVWYRKDKASIDU-UHFFFAOYSA-N check
InChI=1/C6H12N2O4S2/c7-3(5(9)10)1-13-14-2-4(8)6(11)12/h3-4H,1-2,7-8H2,(H,9,10)(H,11,12)
Key: LEVWYRKDKASIDU-UHFFFAOYAA
SMILES: C(C(C(=O)O)N)SSCC(C(=O)O)N

Properties of Cystine:
Chemical formula: C6H12N2O4S2
Molar mass: 240.29 g·mol−1

Molecular Weight: 240.3
XLogP3-AA: -6.3
Hydrogen Bond Donor Count: 4
Hydrogen Bond Acceptor Count: 8
Rotatable Bond Count: 7
Exact Mass: 240.02384922
Monoisotopic Mass: 240.02384922
Topological Polar Surface Area: 177 Ų
Heavy Atom Count: 14
Complexity: 192
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 2
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Specifications of Cystine:
Assay (bromatometric, calculated on dried substance): 99.0 - 101.0 %
Identity (IR-spectrum): passes test
Appearance: white to almost white, fine-crystalline powder
Appearance of solution (100 g/l, hydrochloric acid  2 mol/l): clear and not more intense in color than reference solution Y₇
Spec. rotation (α 20/D, 20 g/l, hydrochloric acid 1 mol/l, previously dried substance): -225 to -215
Chloride (Cl): ≤ 200 ppm
Sulfate (SO₄): ≤ 500 ppm
Heavy metals (as Pb): ≤ 10 ppm
As (Arsenic): ≤ 5 ppm
Ca (Calcium): ≤ 10 ppm
Co (Cobalt): ≤ 5 ppm
Fe (Iron): ≤ 5 ppm
K (Potassium): ≤ 5 ppm
Mg (Magnesium): ≤ 5 ppm
Na (Sodium): ≤ 50 ppm
Pb (Lead): ≤ 5 ppm
Zn (Zinc): ≤ 5 ppm
Ninhydrin - positive substances (LC) (largest single impurity): ≤ 0.2 %
Ninhydrin - positive substances (LC) (Sum of all impurities): ≤ 0.5 %
NH₄ (Ammonium): ≤ 0.01 %
Loss on drying (105 °C; 3 h): ≤ 0.2 %

Synonyms of Cystine:
DL-CYSTINE
923-32-0
cystine
3,3'-disulfanediylbis(2-aminopropanoic acid)
Dicysteine
Cystin
Cystine acid
Cysteine disulfide
(H-Cys-OH)
2-amino-3-[(2-amino-2-carboxyethyl)disulfanyl]propanoic acid
Cystine, L-
NSC13203
MFCD00084652
(-)-Cystine
.beta.,.beta.'-Dithiodialanine
CHEBI:17376
Alanine, 3,3'-dithiobis-
Cystine, DL-
alpha-Diamino-beta-dithiolactic acid
3,3'-Dithiobis(2-aminopropanoic acid)
3,3'-Dithiobis(2-aminopropionic acid)
Bis(.beta.-amino-.beta.-carboxyethyl) disulfide
C6H12N2O4S2
NSC 13203
4746-38-7
cistina
Zystin
MFCD00064228
NSC-13203
NCGC00164531-01
Cystine,(S)
Alanine,3'-dithiodi-
DL-Cystine, 99%
Alanine,3'-dithiobis-
DL-Cystine, free base
90350-38-2
L-3,3'-dithiodialanine
(H-DL-Cys-OH)2
CYSTINE, (L)
Cystine_RamanathanGurudeeban
SCHEMBL10224
CHEMBL366563
BDBM86199
.beta.,.beta.'-Dithiobisalanine
CAS_595
DTXSID50859005
NSC_595
Pharmakon1600-01300099
BCP29195
BBL011587
CAS_67678
NSC_67678
NSC203781
NSC205366
NSC755897
STL163324
AKOS000121517
AKOS016050601
AM81645
CS-W014656
FD21212
MCULE-2293704247
NSC-203781
NSC-205366
NSC-755897
.beta.,.beta.'-dicarboxydiethyldisulfide
3,7-diamino-5-phenyl-phenaziniuchloride
NCGC00164531-02
NCGC00164531-03
AS-66164
K684
SY033311
SY036878
SY038309
.beta.,.beta.'-dicarboxydiethyl disulfide
SBI-0207067.P001
DB-052986
FT-0624467
FT-0625453
FT-0627753
FT-0770594
24645-67-8
(+/-)-3,3'-Dithiobis(2-aminopropionicacid)
Bis(.beta.-amino-.beta.-carboxyethyl)disulfide
C-9765
C01420
L-Cystine-1,1 inverted exclamation marka-13C2
923C320
SR-01000872746
DL-Cystine (H-DL-Cys(1)-OH.H-DL-Cys(1)-OH)
SR-01000872746-1
Q27102343
Z56346947
L-Cystin;Acetylcysteine Impurity A;3,3'-Dithiodialanine
Propanoic acid,3'-dithiobis[2-amino-, [R-(R*,R*)]-
.beta.,.beta.'-Diamino-.beta.,.beta.'-dicarboxydiethyl disulfide
5228F255-51E7-421E-8A05-4687B20118CB
2-amino-3-(2-amino-3-hydroxy-3-oxopropyl)disulfanylpropansäure
2-amino-3-[(2-amino-3-hydroxy-3-oxo-propyl)disulfanyl]propanoic acid
L-Cystine
(-)-Cystine
(2R,2'R)-3,3'-Disulfanediylbis(2-aminopropansäure)
(R,R)-3,3'-Dithiobis(2-aminopropionicacid)
1728094
213-094-5
56-89-3
Acide (2R,2'R)-3,3'-disulfanediylbis(2-aminopropanoïque)
cistina
cystine
cystine 
Cystine (L)-
CYSTINE, L-
Cystine, L- (8CI)
cystinum
HA2690000
L-(-)-Cystine
L-Cystin
L-Cystine
L-Cystine (9CI)
L-Dicysteine
MFCD00064228
oxidized L-cysteine
2-amino-3-(2-amino-2-carboxy-ethyl)disulfanyl-propanoate
2-Amino-3-[(2-amino-2-carboxyethyl)dithio]propanoate
2-Amino-3-[(2-amino-2-carboxyethyl)dithio]propanoic acid
3,3'-dithiobis[2-amino-[R-(R*,R*)]-Propanoate
3,3'-dithiobis[2-amino-[R-(R*,R*)]-Propanoic acid
b,b'-Diamino-b,b'-dicarboxydiethyl Disulfide
Bis(b-amino-b-carboxyethyl) Disulfide
Bis(b-amino-β-carboxyethyl) disulfide
D(+)-3,3'-Dithiobis(2-aminopropanoate
D(+)-3,3'-Dithiobis(2-aminopropanoic acid
β,β'-Dithiobisalanine
(-)-3,3'-Dithiobis(2-aminopropionic acid)
(-)-cystine|cystine|L-dicysteine
(+)-3,3'-Dithiobis(2-aminopropionic acid)
(2R)-2-amino-3-[(2R)-2-amino-2-carboxy-ethyl]disulfanyl-propanoic acid
(2R)-2-amino-3-[(2R)-2-amino-3-hydroxy-3-keto-propyl]disulfanyl-propionic acid
(2R)-2-amino-3-[(2R)-2-amino-3-hydroxy-3-oxopropyl]disulfanylpropanoic acid
(2R)-2-amino-3-[(2R)-2-amino-3-hydroxy-3-oxo-propyl]disulfanyl-propanoic acid
(2R)-2-amino-3-[[(2R)-2-amino-2-carboxyethyl]disulfanyl]propanoic acid
(2R)-2-amino-3-[[(2R)-2-amino-2-carboxy-ethyl]disulfanyl]propanoic acid
(2R)-2-amino-3-[[(2R)-2-amino-3-hydroxy-3-oxo-propyl]disulfanyl]propanoic acid
(2R)-2-amino-3-{[(2R)-2-amino-2-carboxyethyl]disulfanyl}propanoic acid
(2R)-2-azaniumyl-3-[[(2R)-2-azaniumyl-2-carboxylatoethyl]disulfanyl]propanoate
(2R,2'R)-3,3'-disulfanediylbis(2-aminopropanoic acid)
(2R,2'R)-3,3'-disulfanediylbis(2-aminopropanoic acid); L-cystine
(2R,2'R)-3,3'-dithiobis(2-ammoniopropanoate)
(2S)-2-amino-3-[(2S)-2-amino-3-hydroxy-3-keto-propyl]disulfanyl-propionic acid
(2S)-2-amino-3-[(2S)-2-amino-3-hydroxy-3-oxopropyl]disulfanylpropanoic acid
(2S)-2-amino-3-[(2S)-2-amino-3-hydroxy-3-oxo-propyl]disulfanyl-propanoic acid
(2S,2'S)-3,3'-disulfanediylbis(2-aminopropanoic acid)
(2S,2'S)-3,3'-dithiobis(2-aminopropanoic acid)
(Cys)₂
(H-Cys-OH)2
(H-Cys-OH)2 (Disulfide bond)
(R-(R*,R*))-3,3'-Dithiobis(2-aminopropanoic acid)
(R,R)-3,3'-dithiobis(2-aminopropanoic acid)
(R,R)-3,3'-dithiobis(2-aminopropanoic acid); L-α-Diamino-β-dithiolactic acid; L-Dicysteine; ??,??'-dithiodialanine
(R,R)-3,3'-dithiobis(2-aminopropanoic acid); L-α-Diamino-β-dithiolactic acid; L-Dicysteine; β,β'-dithiodialanine
(R,R)-3,3'-dithiobis(2-aminopropionic acid)
(S,S)-3,3'-Dithiobis(2-aminopropionic acid)
??,??'-dithiodialanine
[56-89-3]
1728093
1888247
1-Cystine
24645-67-8
2-amino-3-(2-amino-2-carboxy-ethyl)disulfanyl-propanoic acid
3,3'-dithiobis(2-aminopropanoic acid)
3,3'-Dithiobis(2-aminopropanoic acid), (R-(R*,R*))-
3,3'-Dithiobis-L-alanine
3,3'-Dithiodialanine
BIS(β-AMINO-β-CARBOXYETHYL) DISULFIDE
Bis(β-amino-β-carboxyethyl)disulfide
Cys
CYSTEINE DISULFIDE
Cystine (USAN)
Cystine acid
D03636
dicysteine
E921
EINECS 206-486-2
Gelucystine
H-(Cys)2-OH
H-(Cys)2-OH, (-)-3,3'-Dithiobis(2-aminopropionic acid)
H-(Cys)2-OH; (-)-3,3'-Dithiobis(2-aminopropionic acid)
H-D-(Cys)_2-OH
β,β'-dithiodialanine
l(-)-cystine
L-?Cystine
L-Alanine, 3,3'-dithiobis-
L-Cysteine disulfide
L-Cystine - CAS 56-89-3 - Calbiochem
l-cystine bisamide dihcl
L-cystine zwitterion
L-Cystine, Cell Culture Reagent
L-Cystine, non-animal source
Lithium 2,4-dihydroxy-3,3-dimethylbutanoate
L-α-Diamino-β-dithiolactic acid
MFCD00002610
NCGC00166006-01
NCGC00166007-01
Propanoic acid, 3,3'-dithiobis(2-amino-, (R-(R*,R*))-
RAC-L-CYSTINE
α-Diamino-β-dithiolactic acid
β,β'-diamino-β,β'-dicarboxydiethyl disulfide
β,β'-Diamino-β,β'-dicarboxydiethyldisulfide
β,β'-Dithioalanine, L-
β,β'-dithiodialanine
β,β'-dithiodialanine