Chondroitin sulfate (formally chondroitin sulphate) (more correctly the plural) is a key structural component of cartilage. It is a complex polymer of N-acetylgalactosamine and glucuronic acid sulfonated at multiple positions and in vivo is complexed with structural proteins as well as being a cation associated with sodium, potassium, magnesium or more often calcium anions. It is not a sulphate !
Low-sulfated chondroitin sulfates are found naturally in higher animals with at the other extreme over sulfated chondroitin sulfates not being found naturally in mammals. Low-sulfated chondroitin sulfate is the main component of acidic glycosaminoglycans in blood from patients with Hurler's syndrome who excrete excessive amounts of dermatan sulfate and heparan sulfate.  There is complex regulation of the degree of sulfonation in biologically active polymers which can depend upon their regulatory or structural role in combination with their complexed proteins.
- Chondroitin 4-sulfate (chondroitin 4-sulphate, chondroitin sulfate A, chondroitin sulphate A)
- Found at small concentrations in normal human plasma and urine.
- Chondroitin-6-sulfate (chondroitin-6-sulphate, chondroitin sulfate C, chondroitin sulphate C)
- Chondroitin-2,6-sulfate (chondroitin-2,6-sulphate, chondroitin sulfate D, chondroitin sulphate D)
- The commonest structural form
- Chondroitin-2,4-sulfate (chondroitin-2,4-sulphate, chondroitin sulfate D, chondroitin sulphate D)
The unsulfonated polyglycan has been called chondroitin. These are combined with proteins, usually at a serine residue. Each sugar is attached to a protein serine by a specific enzyme, allowing for multiple levels of control over synthesis. Such synthesis usually takes place in the Golgi apparatus, with the important exception that xylose which is key to the four monosaccharide primer that is necessary to initiate protein attachment ( Xyl - Gal - Gal - GlcA) is attached in the endoplasmic reticulum. Important proteins it is complexed with include:
Chondroitin sulfate appears to be important in cartilage resistance to compression, and this is explained by the highly charged sulfate groups generating electrostatic repulsion. There is a strong negative association between the amount of chondroitin sulfate in joint cartilage and the presence of clinical osteoarthritis. The low ability of CNS neuroregeneration may be related to chondroitin sulfate's properties in the neuronal extracellular mileau. Its association with regulatory proteins suggests potential pharmacological properties independent of its properties in cartilage.
Widely used to treat osteoarthritis due to its status as a natural molecule, the objective part of the evidence base for clinical effectiveness is somewhat challenging in this context, and for pain relief it is unlikely to be benefical over placebo. However it has an extremely low toxicity and accordingly will have excellent placebo properties in its own right. This is rather important considering the potential toxicity of more clinically effective alternatives. Preparations have variable composition.
- ↑ Hata RI, Ohkawa SI, Nagai Y. Low-sulfated chondroitin sulfate in human blood and urine. Biochimica et biophysica acta. 1978 Oct 3; 543(2):156-66.
- ↑ Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. The New England journal of medicine. 2006 Feb 23; 354(8):795-808.(Link to article – subscription may be required.)
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