| Chondroitin Sulfate |
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| glycosaminoglycans | |
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Chondroitin sulfate is a sulfated Glycosaminoglycan (GAG) composed of a chain of alternating sugars ( N-acetyl-galactosamine and Glucuronic Acid ). It is usually found attached to proteins as part of a Proteoglycan . A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Understanding the functions of such diversity in chondroitin sulfate and related glycosaminoglycans is a major goal of Glycobiology . Chondroitin sulfate is a major structural component of Cartilage and provides much of its resistance to Compression . Along with Glucosamine , chondroitin sulfate has become a widely used Dietary Supplement for treatment of Osteoarthritis . TERMINOLOGY Chondroitin sulfate was originally isolated well before the structure was characterised, leading to changes in terminology with time. 1 Free PDF online Early researchers identified different fractions of the substance with letters.
Although the name "chondroitin sulfate" suggests a Salt with a sulfate Counter-anion , this is not the case, as sulfate is covalently attached to the sugar. Rather, since the molecule has multiple negative charges at physiological pH, a Cation is present in salts of chondroitin sulfate. Commercial preparations of chondroitin sulfate typically are the sodium salt. Barnhill et al. have suggested that all such preparations of chondroitin sulfate be referred to as "sodium chondroitin" regardless of their sulfation status.3 STRUCTURE Chondroitin sulfate chains are unbranched (GlcA) and N-acetyl-D-galactosamine (GalNac). GlcA residues are sometimes epimerized into L-iduronic Acid (IdoA); the resulting chain is then referred to as Dermatan Sulfate . Protein Attachment Chondroitin sulfate chains are linked to hydroxyl groups on Serine residues of certain proteins. Exactly how proteins are selected for attachment of glycosaminoglycans is not understood. Empirically, glycosylated serines are often followed by a glycine and have neighboring acidic residues, but this motif does not always predict glycosylation. Attachment of the GAG chain begins with four monosaccharides in a fixed pattern: Xyl - Gal - Gal - GlcA. Each sugar is attached by a specific enzyme, allowing for multiple levels of control over GAG synthesis. Xylose begins to be attached to proteins in the Endoplasmic Reticulum , while the rest of the sugars are attached in the Golgi .4 Sulfation Each monosaccharide may be left unsulfated, sulfated once, or sulfated twice. Most commonly the hydroxyls of the 4 and 6 positions of the N-acetyl-galactosamine are sulfated. Sulfation is mediated by specific sulfotransferases. FUNCTION Chondroitin's functions largely depend on the properties of the overall proteoglycan of which it is a part. These functions can be broadly divided into structural and regulatory roles. However, this division is not absolute and some proteoglycans have both structural and regulatory roles (see Versican ). Structural Chondroitin sulfate is a major component of extracellular matrix. As such it is important in maintaining the structural integrity of the tissue. This function is typical of the large aggregating proteoglycans: Aggrecan , Versican , Brevican , and Neurocan . As part of Aggrecan , chondroitin sulfate is a major component of Cartilage . The tightly packed and highly charged sulfate groups of chondroitin sulfate generate Electrostatic Repulsion that provides much of the resistance of cartilage to compression. Loss of chondroitin sulfate from the cartilage is a major cause of osteoarthritis. Regulatory Chondroitin sulfate readily interacts with proteins in the extracellular matrix due to its negative charges. These interactions are important for regulating a diverse array of cellular activities. Although these functions are not as well characterized as those of Heparan Sulfate , new roles continue to be discovered for the chondroitin sulfate proteoglycans. In the nervous system, chondroitin sulfate proteoglycans regulate the growth and development of the nervous system as well as the nervous system response to injury. MEDICAL USE Chondroitin is an ingredient found commonly in Dietary Supplements used as an Alternative Medicine to treat osteoarthritis. It is commonly sold together with Glucosamine . Pharmacology The dosage of oral chondroitin used in human clinical trials is 800-1200 mg per day. Most chondroitin appears to be made from extracts of cartilaginous cow and pig tissues (cow Trachea and pig ear and nose), but other sources such as Shark , fish and bird cartilage are also used. Since chondroitin is not a uniform substance, and is naturally present in a wide variety of forms, the precise composition of each supplement will vary. While it is a prescription or over-the-counter drug in 22 countries, chondroitin is regulated in the U.S. as a food product by the Food And Drug Administration . As a result, there are no mandatory standards for formulation, and no guarantee that the product is correctly labelled. Adebowale et al. reported in 2000 that of 32 chondroitin supplements they analysed, only 5 were labeled correctly, and more than half contained less than 40% of the labeled amount.5. However, United States Pharmacopoeia (USP) testing standards now exist for the identification and quantification of chondroitin. Clinical studies have not identified any significant side effects or overdoses of chondroitin sulfate. Clinical Trials Due to the popularity of the glucosamine-chondroitin supplement and the lack of reliable information about their usefulness in treating osteoarthritis 6 , the National Institute Of Health funded a study to test the effects of chondroitin and glucosamine on osteoarthritis of the knee. This Multicenter , placebo-controlled, double-blind, 6-month-long trial found that glucosamine plus chondroitin had no Statistically Significant effect on symptoms of osteoarthritis. 7. The control group of patients who took celecoxib did have a statistically significant improvement in their symptoms. These results indicate that glucosamine and chondroitin do not effectively relieve osteoarthiritic pain. Although the study found no overall effect for the supplements, a Secondary Analysis of a subgroup of patients suggested that the supplements taken together helped people with more severe pain. REFERENCES EXTERNAL LINKS
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