Glycosaminoglycans heparan-sulfate

Degradation of the glycosaminoglycan heparan sulfate by lysosomal enzymes, indicating sites of enzyme deficiencies in some representative mucopolysaccharidoses. 

HSV-1 vims entry is mediated by multiple glycoproteins present in the envelope and is a rather complex process. Initial adhesion to the cellular membrane is mediated by the interaction of gC and gB with glycosaminoglycan heparan sulfate. Subsequently, gD binds to a specific cellular receptor, either a member of the TNF receptor family [herpes vims entry mediator A (HveA)], immunoglobulin superfamily (HveB, HveC), or 3-O-sulfated heparan sulfate. Then, the vims enters the cell through membrane fusion promoted by the gH/gL complex and gB (117). 

Connective tissue, which consists primarily of fibroblasts, produces extracellular matrix materials that surround cells and tissues, determining their appropriate position within the organ (see Chapter 49). These materials include structural proteins (collagen and elastin), adhesive proteins (fibronectin), and glycosaminoglycans (heparan sulfate, chondroitin sulfate). The unique structures of the proteins and carbohydrates found within the extracellular matrix allow tissues and organs to carry out their many functions. A loss of these supportive and barrier functions of connective tissue sometimes leads to significant clinical consequences, such as those that result from the microvascular alterations that lead to blindness or renal failure, or peripheral neuropathies in patients with diabetes mellitus. 

There are other glycosaminoglycans. Hyaluronic acid [9004-61-9] occurs both free and in noncovalent association with proteoglycan molecules. Heparin [9005-49-6] and heparan sulfate [39403-40-2] also known as heparitin sulfate [9050-30-0] occur in mast cells and in the aorta, Hver, and lungs. 

Danaparoid (Orgaran mean MW, 6,000 Da) is a mixture of nonheparin glycosaminoglycans derived from pig gut (dermatan sulfate, heparan sulfate, chondroitin sulfate). Die anti-Xa/anti-IIa ratio (22 1) is even greater than seen with LMWH. Die anti-IIa effect may be mediated in part by dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II. 

Fig. 34.—Circular Dichroism of Glycosaminoglycans (a) Hyaluronic Acid (b) Heparan Sulfate from Normal Mammalian Tissue (c) Chondroitin 4-Sulfate (d) Dermatan Sulfate ...

Contamination from other L-iduronic acid-containing glycosaminoglycans (dermatan sulfate and heparan sulfate species) cannot usually be lowered below the 1-2% level, unless repeated precipitations or treatments with resin are made. As will be discussed in Section VIII, extensive... 

It is likely that the predominantly positively charged amino acids of TAT and other CPPs will interact with anionic components on the surface of the cell membrane (85). This idea is supported by the observation that cell association with CPP liposomes in glycosaminoglycan-deficient Chinese hamster ovary (CHO) cells is greatly reduced and is competitively inhibited by the presence of heparin (88,93). Furthermore, the removal of the heparan sulfate chains by the action of glycosaminoglycan lyase also suppressed the transduction of the TAT protein (94). 

Six major classes of glycosaminoglycans There are six major classes of glycosaminoglycans. These include chondroitin 4- and 6-sulfates, keratan sulfate, dermatan sulfate, heparin, heparan sulfate, and hyaluronic acid. 

A glycosaminoglycan isolated from lobsters was examined with heparin lyase and heparan sulfate lyase.275 It was degraded much less extensively than beef-liver heparin by the former, and not degraded by the latter, indicating a structure intermediate between those of heparin and heparan sulfate. Heparan sulfates from three species of mollusks219 were found to be resistant to heparin lyase action. With heparan sulfate lyase, similar oligosaccharides in different proportions were obtained. Comparison with the products from bovine-pancreatic heparan sulfate showed the same oligosaccharides. 

Robinson MJ, Tessier P, Poulsom R, Hogg N. 2002. The S100 family heterodimer, MRP-8/14, binds with high affinity to heparin and heparan sulfate glycosaminoglycans on endothelial cells. J Biol Chem 277(5) 3658—3665. 

Figure 2. Structures of the glycosaminoglycans and their linkage regions to protein. Two disaccharide repeating units are shown to emphasize the microheterogeneity that exists in some cases. Heparan sulfate and heparin show many structural similarities. However, heparan sulfate contains more GlcNAc(a-1 — 4)GlcUA repeating units fewer glucosamine residues are N-sulfated, and few iduronic acid residues are sulfated at C2.

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