Glycosaminoglycans hydrolysis

Dermatan sulfate, also termed chondroitin sulfate B, a related glycosaminoglycan constituent of connective tissue, was known to be composed of galactosamine and a uronic acid, originally believed to be glucuronic acid but then claimed to be iduronic acid based largely on color reactions and paper chromatography. However, the d or L-enantiomer status of the latter monosaccharide was not clear. Jeanloz and Stoffyn unequivocally characterized the monosaccharide as L-iduronic acid by consecutive desulfation, reduction, and hydrolysis of the polysaccharide, followed by isolation of the crystalline 2,3,4-tri-0-acetyl-l,6-anhydro-/ -L-idopyranose, which was shown to be identical to an authentic specimen synthesized from 1,2-0-isopropylidene-/ -L-idofuranose.34... 

Aldurazyme (tradename, also known as laronidase) is a recombinant version of one polymorphic variant of the human enzyme a-L-iduronidase. It was approved for general medical use in the USA in 2003 and is indicated for the treatment of patients with certain forms of the rare inherited disease MPS I. MPS I is caused by a deficiency of a lysosomal a-L-iduronidase, which normally catalyses the hydrolysis of terminal a-L-iduronic acid residues from the glycosaminoglycans dermatan sulfate and heparin sulfate. The deficiency results in accumulation of the glycosaminoglycans throughout the body, causing widespread cell and tissue dysfunction. 

Biosynthesis and degradation of glycosaminoglycans biosynthesis of collagen, mineralization and demineralization of bone. Fatty acid synthesis and triglyceride storage in adipocytes promoted by insulin and triglyceride hydrolysis and fatty acid release stimulated by glucagon and adrenaline (epinephrine). 

Glycosaminoglycans are solubilized from stromal or other tissues by extracting the source tissue with dilute acid or alkali. Hyaluronan is electrostatically bound to specific proteins called hyaladherins, which possess a structural domain of -100 amino acids termed a link module. Other glycosaminoglycans are O-linked to serine and threonine residues of polypeptides and these bonds hydrolyze before the rest of the polysaccharide. The protein moiety precipitates when trichloroacetic acid or ammonium sulfate is added to the cooled mixture. The composition of the GAGs (including hyaluronan) was identified by chromatographic separation of the purified polysaccharides, followed by their hydrolysis in boiling 1.0 M HC1 for 2 1 h and identification of the individual monosaccharide components. 

Proteoglycans undergo continuous turnover at rates dependent upon the nature of the proteoglycan and tissue location. Their half-life is between one and several days. Degradation of proteoglycans is initiated by proteolytic enzymes that release glycosaminoglycans the latter are subsequently degraded by lysosomal enzymes. Some of the products of hydrolysis (e.g., dermatan sulfate and heparan sulfate) are excreted in the urine. 

Hydrolyzed glycosaminoglycans Synonyms Hydrolyzed mucopolysaccharides Definition Mixt. of polysaccharides derived from hydrolysis of animai connective tissue consists essentiaiiy of giucosamine gluconate Uses Humectant moisturizer, skin conditioner Manuf./Distrib. Active Organics http //www.activeorganics.com. Am. Labs http //www.americaniaboratories.com. Arch Personal Care Prods. 

Some years ago the hypothesis was advanced that all forms of cell proliferation depend upon one fundamental interaction between the cell and its immediate environment [5]. The hypothesis may be stated as follows All cells in the body are embedded in a highly viscous environment of ground substance that physically restrains their inherent tendency to proliferate proliferation is initiated by release of hyaluronidase from the cells, which catalyzes the hydrolysis of the glycosaminoglycans in the immediate environment and allows the cells freedom to divide and to migrate within the limits of the alteration proliferation continues as long as hyaluronidase is being released, and stops when the production of hyaluronidase stops or when the hyaluronidase is inhibited, and the environment is allowed to revert to its normal restraining state. 

Riemer, T., Nimptsch, A., Nimptsch, K., and Schiller, J. 2012. Determination of the glycosaminoglycan and collagen contents in tissue samples by high-resolution H NMR spectroscopy after DCl-induced hydrolysis. Biomacromolecules, 13 2110-2117. 

Values for Km and have been determined for the degradation of chondroitin 4- and 6-sulphates, chondroitin 4-sulphate proteoglycan, dermatan sulphate, and hyaluronic acid by a chondroitin sulphate lyase ABC obtained from Proteus vulgaris. The hydrolysis of chondroitin 4-sulphate by the enzyme was inhibited by hyaluronic acid, but not by keratan sulphate. The findings were discussed in connection with the use of chondroitin sulphate lyase ABC as a reagent for the degradation of tissue glycosaminoglycans. 

Polylactic-co-glycolic acid (PLGA) and glycosaminoglycans Satisfactory biocompatibility Good mechanical strength polymer hydrolysis, inconsistent biodegradation rates Munirah et al. (2008)... 

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