Chondroitin sulfate
IUPAC: poly [ (N -acetyl- D- galactosamine - 4-O- hydrogen sulfate ) - ( L-iduronic acid ) ]
- 24967-94-0
- 39455-18-0 (sodium salt)
Copolymer biopolymer, polysaccharide
M01AX25
Antiarthrotikum
Chondroitin sulfate (also Chondritinsulfat ) is a biological macromolecule. The substance formed by the chondroblasts is an important component of cartilage and contributes to the resistance against compression at.
Chemically it is a mixture of sulfated glycosaminoglycans (GAGs ), also called mucopolysaccharides. In the polymer chains, the Zuckerabkömmlinge N -acetylgalactosamine ( GalNAc ) and glucuronic alternate.
- 2.1 Structural Function
- 2.2 Regulating function
- 4.1 cartilage regeneration, cartilage protection
- 4.2 ophthalmology and urology
- 4.3 Local anti-inflammatory application
Chemical structure
Chondroitin sulfate chains are unbranched polysaccharides of variable length. They always consist of two alternating monosaccharides: D- glucuronic acid ( GlcA ) and N- acetylgalactosamine ( GalNAc ). Here, the glucuronic acid with β - 1 → 3 GalNAc and GalNAc is linked to glucuronic acid → 4 -glycosidic β -1. A chondroitin chain can consist of over 100 sugar units, which may be sulphated to varying degrees, and at the positions C6 and / or C4 of the GalNAc. Epimerization at C5 of glucuronic acid to iduronic acid, one speaks of dermatan sulfates. Understanding the striking diversity of chondroitin sulphate and the related glycosaminoglycan is one of the objectives of glycobiology.
Sulfation
Each simple sugars can either without, be present with one or two sulfate groups. Most commonly the hydroxyl groups of carbon atoms of 4 or 6 of N-acetyl- galactosamine are provided with a sulfate group. The sulfation is catalyzed by various sulfotransferases. The sulfation is an average of 0.8 based on the disaccharide.
The following types are distinguished:
The typing the letters A to E comes from the time when it was already isolated chondroitin sulfate, the structure was not yet known. The classification of dermatan under the chondroitin sulfates as Chondraoitinsulfat B is now regarded as a misnomer, since this compound is derived not from the glucuronic acid, but by the iduronic acid. The most common chondroitin sulfates are the types A, B and C.
The previously common name Chondroitin without " sulfate ", which was used to describe a chain without or with very few sulfate groups is no longer in place.
Although the name suggests that chondroitin sulfate is a salt with a sulfate anion, the sulfate is covalently linked to the sugar. Since the molecule has more negative charges at physiological pH, it is located in the salts of chondroitin sulfate present as anion. The commercial product of chondroitin sulfate is usually its sodium salt. Barnhill et al. have suggested that all of chondroitin sulfate - products should be referred to as " sodium chondroitin ," without regard to the sulphate bonds.
A synthetic nachsulfatierte variant is the chondroitin polysulfate ( " oversulfated chondroitin sulfate ", English " oversulfated chondroitin sulfate", OSCS ). The additional sulfation of the anti-inflammatory ( anti-inflammatory ) is amplified effect of the substance. Chondroitin also has an anti-clotting ( anticoagulant ) and fibrinolytic activity.
Protein binding
Biologically chondroitin sulfate is commonly bound to proteins prior to, as part of a proteoglycan. The binding of chondroitin sulfate chains occurs at the hydroxyl groups of the serine residues of certain proteins. Exactly how proteins are selected for binding to glycosaminoglycans, is not yet understood. Glycosylated serine residues often follow glycine residues, are found in the vicinity of acidic amino acid residues.
As a link to the GAG chain is always the same sugar chain of three sugar units:
| Ser -O- Xyl -Gal -Gal - GlcA ... | Each sugar is attached by a specific enzyme, creating a multi-layered control of GAG synthesis is allowed. Xylose is bound to the proteins in the endoplasmic reticulum, and the rest of the sugar is transferred to the Golgi apparatus.
Function
The function of the chondroitin is highly dependent on the properties of the entire proteoglycan, to which it belongs. Chondroitin proteoglycans have both structural and regulatory functions.
Structural function
Chondroitin proteoglycans put together with collagen essential components of the extracellular matrix; they effect the structural integrity of the tissue. Typical representatives are aggrecan, versican, and neurocan Brevican.
As part of aggrecan chondroitin sulfate forms a large part of the cartilage. The tightly packed, highly charged sulfate groups leading to electrostatic repulsion of the individual chains (see Coulomb's law ), which caused a large part of the resistance of cartilage to compression. Loss of chondroitin sulfate from the cartilage is one of the most common causes of osteoarthritis.
Regulating function
Also due to the negative charges occurs chondroitin easily interact with other proteins of the extracellular matrix. These interactions are important for the regulation of a variety of cellular processes. Compared to heparan sulfate, another of the extracellular matrix proteoglycan, still little is known about the role of chondroitin sulfate proteoglycans is known. It is known that chondroitin sulfate growth and development of the nervous system regulates as well as its response to injury.
Extraction
Chondroitin sulfate is largely derived from cartilage tissue of cattle, pigs and sharks. Other species of fish and birds can be cartilage supplier.
Use
Cartilage regeneration, cartilage protection
Chondroitin sulfate is medically and nutritionally used in the treatment of degenerative joint disease ( osteoarthritis ), for example, the hip, knee, or fingers. Likewise, chondroitin sulfate is taken as a food supplement to maintain healthy cartilage and prevent arthritic wear and tear ( chondroprotection ). Frequently it is being combined with glucosamine. The application is based on the idea that the supplied chondroitin sulfate is " built into" the cartilage. In vitro (ie, outside of a living organism), chondroitin sulfate has an anti-inflammatory effect.
Chondroitin sulfate is commonly used in oral doses of 800-1200 mg per day. A dose from the pharmacological activity occurs could not be determined due to insufficient data. Since chondroitin is not a uniform substance, and it is present in nature in a wide range of different forms, the composition of finished products varies accordingly. There are in the food no mandatory standards for the composition. In the U.S., was revealed in 2000 that a high proportion chondroitinhaltiger dietary supplements with regard was labeled false or misleading to the Chondroitingehalt.
For oral bioavailability of chondroitin sulfate and its metabolism, there is no valid data.
- In metastudies the significant improvement of certain targets (eg, Lequesne index, WOMAC index, VAS) was found under a arthrosis treatment with chondroitin sulfate.
- 2006 was initiated by the National Institutes of Health ( NIH ) of the United States, a multicenter, placebo-controlled, six -month -blind study on the efficacy of chondroitin and glucosamine in osteoarthritis of the knee. She presented no statistically significant effect on the symptoms of osteoarthritis in patients with minor aches and pains permanently. Joint swelling were reduced. Treatment effects were observed in a subgroup of patients with moderate to severe pain, but the significance was not valid due to the small number of patients in this subgroup.
- The result of recent meta-studies ( 2007 & 2010) was that chondroitin, glucosamine, and their combination have no clinically relevant effects on perceived joint pain or on joint wear.
- A double-blind, randomized, placebo-controlled study of 2013 conducted by the University of Sydney with 605 subjects ( age 45-75 years, osteoarthritis of the knee ) was able to observe a statistically significant attenuation of the decrease in joint space. It has been used here for 2 years daily 2 x 750 mg glucosamine sulfate and 2 x 400 mg chondroitin sulfate. A decrease in the joint was in all groups [1 ) 2 x 750 mg glucosamine, 2) chondroitin sulfate 2 x 400 mg 3) 750 mg glucosamine sulfate 2 x 2 x 400 mg of chondroitin sulfate, 4) placebo ] - with no significant difference between the groups - are observed.
In the usual oral doses up to 1200 mg per day of chondroitin sulfate is well tolerated. No serious side effects were noted by chondroitin sulfate in this dose range in clinical trials.
The intramuscular and intra-articular administration of chondroitin sulfates has been displaced by better tolerated Hyaluronate. A decades- long intraarticularly -applied as osteoarthritis remedy chondroitin preparation was taken in 1992 due to severe anaphylactic and thromboembolic side effects from the market.
Ophthalmology and Urology
Aqueous Chondroitinsulfatlösungen be in ophthalmology, in combination with hyaluronate, during procedures used on the eye to moisten the corneal endothelium and protect. As Blasenspüllösung chondroitin sulfate is used to restore the bladder mucosa, such as when caused by chronic inflammation (interstitial cystitis) is damaged.
Local anti-inflammatory application
One area of application for chondroitin ( " oversulfated chondroitin sulfate ") is the topical treatment of blunt injuries and superficial veins ( phlebitis ). In animal studies, and skin models has been shown that chondroitin is able to penetrate through the skin into the underlying tissues. There should exert its anti-inflammatory ( anti-inflammatory ) effect. Chondroitin polysulfate is applied as an ointment, cream or gel.
Heparin scandal
In 2008, it was released worldwide on the incident known as " heparin scandal " after Chinese drug manufacturers had the drug heparin with oversulfated chondroitin cheaper ( chondroitin ) "stretched". As a result, numerous serious side effects were encountered, some of them fatal.
Commercial preparations
- Monopreparations: Condrosulf (A, CH), Gepan instill (D), Structum (CH)
- Combination products with additional nutrients: Glusatin (D, A), Arthrovitan (D), Arthrobel (D), CondroTect (D), Duovital (D), Orthomol Arthro (D), Orthoexpert (D)
- Combination products with hyaluronic acid: PROVISC (D), Viscoat (D)
Hirudoid (D), Sanaven (D), combined with salicylic acid: Mobilat DuoAktiv (D)