Hyaluronan glycosaminoglycan

Figure 4-11 The repeating disaccharide units of hyaluronan and other glycosaminoglycans. See Fransson108 and Hardingham and Fosang.107...

Most of the polysaccharides of interest in this text are termed glycosaminoglycans, polymers that contain an amino sugar in the repeat unit. Glycosaminoglycans that are abundant in mammalian tissues include hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparin-heparan sulfate (see Table 2.4). Most of these glycosaminoglycans,... 

The space-filling character of glycosaminoglycans appears to be important in morphogenesis, particularly in the development of the skeleton. During these developmental processes, the presence of hyaluronan appears to facilitate the migration of cells. This effect is stopped by the removal of hyaluronan by hyaluronidase and by its replacement with aggregating proteoglycans. 

Heparin/heparan, hyaluronan, and chondroitin are three prevalent glycosaminoglycans. Vertebrates use glycosaminoglycans in structural, recognition, adhesion, and signaling roles. Chemical synthesis of naturally occurring polysaccharides is considered to be impractical. Most polysaccharides, especially those from bacteria origins, are obtained by purification from natural sources or from cell culture, enzymatic approaches have been increasingly applied to obtain some structures. 

Kobayashi S, Morii H, Itoh R, Kimura S, Ohmae M. Enzymatic polymerization to artificial hyaluronan a novel method to synthesize a glycosaminoglycan using a transition state analogue monomer. J. Am. Chem. Soc. 2001 123 11825-11826. 

During these years, our work laid the foundation for future studies on the effect of elastoviscous solutions of hyaluronan on the migration, proliferation and function of white blood cells, and how such solutions affect some functions of the immune system. We discovered that hyaluronan regulates the synthesis of glycosaminoglycans in in vitro systems, and regulates inflammation and tissue regeneration in adult animal models and tissues. All these studies laid the theoretical foundation for the therapeutic applications of hyaluronan. 

Hyaluronan (hyaluronic acid) is the simplest glycosaminoglycan. It consists of alternating GlcA and GlcNAc residues which are (/31-3) and (/31 ) linked, respectively (O Fig. 15) [172, 173,174,177]. Hyaluronan is not sulfated and is not bound to protein, thus it is not a component of proteoglycans. 

Hyaluronan is the most common negatively charged glycosaminoglycan in the human vitreous humor, and is known to interact with polymeric and liposomal DNA complexes, where hyaluronan solutions have been shown to decrease the cellular uptake of complexes.This is useful for enhancing the availability and retention time of drugs administered to the eye. It is immunoneutral, which makes it useful for the attachment of biomaterials for use in tissue engineering and drug delivery... 

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. 

Interestingly, the secretion of FGF family members that mediate tissue repair resembles IL-1 secretion, that is, not involving the Golgi. The FGF family proteins also bind to their receptors by P-barrel structures that interact with a glycan (in this case known to be heparin) during activation. Hyaluronan and heparin are glycosaminoglycans (Sect. 6.3.1). 

Hyaluronan Formerly known as hyaluronic acid a glycosaminoglycan composed of alternating residues of glucuronic acid and N-acetylglucosamine. Hyaluronan is not sulfated nor is it covalently linked to a protein. 

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