Chondroitinase C

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Introductions

A chondroitinase that acts upon chondroitin sulfate C and hyaluronic acid was isolated from Flavobacterium heparinum. This enzyme was seperated from constitutional chondroitinase AC and an induced chondroitinase B also present in extracts of F. heparinum previously grown in the presence of chondroitin sulfates A, B or C. The enzyme acts upon chondroitin sulfate C producing tetrasaccharide plus an unsaturated 6-sulfated disaccharide (delta Di-6S), and upon hyaluronic acid producing unsaturated nonsulfated disaccharide (delta Di-OS). Chondroitin sulfate A is also degraded producing oligosaccharides and delta Di-6S but not delta Di-4S. The chondroitinase C is also distinguished from the chondroitinases B and AC by several properties, such as effect of ions, temperature for optimal activity, and susceptibility to increasing salt concentrations. The substrate specificity of the chondroitinase C is different from that of any other chondroitinase or hyaluronidase described so far.

Functions

Chondroitinase C specifically degrades the glycosaminoglycans in the extracellular matrix components, and the product is an unsaturated disaccharide, which is a tool enzyme for studying the structure of glycosaminoglycans. Chondroitin sulfate lyase has several important uses. In basic research, it is used to construct gene libraries of disaccharides and oligosaccharides, to identify isotopes of chondroitin sulfate, and to study the structure and properties of glycosaminoglycans. In the field of clinical applications, the research has been very active in recent years, including the prevention and treatment of diseases related to extracellular matrix metabolism, such as macrosomia, and the study of the relationship between glycosaminoglycans and tumorigenesis, replacing collagenase and papain in chemical myelolysis.

Physiological Functions

Chondroitinase C specifically hydrolyzes the chondroitin sulfate proteoglycan which is thought to play an important role in maintaining the vitreous gel state while it is also involved in molecular adhesion at the vitreoretinal interface.

Production

At present, the pharmaceutical and health care industries have a great demand for low molecular weight chondroitinase C, which is prepared by acid hydrolysis, ion exchange and enzymatic digestion. The first two methods require more complex experimental equipment and more difficult to control and bring environmental pollution and high production costs. Enzymatic digestion method has convenient control, simple equipment, low production cost advantages.

Chondroitin Sulfate ABC Enzyme

ABC enzyme degrades chondroitin sulfate A, chondroitin sulfate B (dermatan sulfate) and chondroitin sulfate C. This enzyme acts on the β1-4 glycosides between the disaccharide repeating units and cuts them off by a β-elimination mechanism. The products of the degradation reaction are oligosaccharides, mainly unsaturated disaccharides. Chondroitin sulfate can be quantified by measuring the unsaturated disaccharide product.

Outlook

Chondroitinase C may be a good drug candidate. The biological activity of chondroitinase is due to its ability to act on chondroitin sulfate proteoglycans (CSPGs). CSPGs are needed for normal functioning of the body. An increase or decrease in the level of CSPGs results in various pathological conditions. Chondroitinase is useful in conditions where there is an increase in the level of CSPGs, namely spinal cord injury, vitreous attachment and cancer. Research focusing on the development of suitable carrier systems to deliver chondroitinase is needed so that the pharmacological activity observed in in vitro and preclinical studies can be translated to clinical use. Further studies on chondroitinase distribution also need to be focused on in order to discover chondroitinases with the desired properties.