Glycosaminoglycans specification

Harris, E.N., J.A. Weigel, and P.H. Weigel, Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE). Journal of Biological Chemistry, 279 (35) 36201-36209,2004. 

FIGURE 9.32 Proteoglycans serve a variety of functions on the cytoplasmic and extracellular surfaces of the plasma membrane. Many of these functions appear to involve the binding of specific proteins to the glycosaminoglycan groups. 

EC-SOD is a copper-zinc enzyme located on endothelial cell surfaces. It is believed that EC-SOD binds to the vasculature via specific glycosaminoglycans — probably heparan sulphate on the endothelium. The association of EC-SOD with endothelial cell surfaces may indicate a cell-specific protective role. Eig/ity per cent of SOD activity in control, noninflamed synovial fluid is due to EC-SOD and its concentration is decreased by 50% in RA fluid (Marklund etal., 1986). 

The first is glycosaminoglycan, a compound produced by the body that coats the epithelial cells of the bladder. This compound essentially separates the bladder from the urine by forming a protective layer against bacterial adhesion.14 A second compound known as Tamm-Horsfall protein is secreted into the urine, and prevents E. coli from binding to receptors present on the surface of the bladder. Other factors implicated in contributing to host defense mechanisms include immunoglobulins, specifically IgA, and lactobacilli, bacteria that are part of the normal vaginal flora.13,15... 

A classical, and still most useful, physicochemical parameter for characterizing glycosaminoglycans is their specific optical rotation. For pure heparins from common sources, [a]80 = + 45 to + 53 ° (see Table II). The actual value depends on the relative proportions of monosaccharide constituents (that is, the L-idosyluronic acid residues make a less positive contribution than the n-glucosyluronic residues), and on the degree of sulfation of the preparation (that is, although sulfate groups may have little direct influence on the molecular rotation, they lower the value by acting as diluents ). 

Through the combined approach of l.c. and the sequential applications of specific glycosaminoglycan-lyases, it is possible to determine the levels of several different glycosaminoglycans in the same tissue-sample. Thus, Gurr and coworkers demonstrated that hyaluronate, chondroitin sulfate... 

Sulfation of the carbohydrate chain occurs after the monosaccharide to be sulfated has been incorporated into the growing carbohydrate j chain. The source of the sulfate is 3 -phosphoadenosyl-5 -phospho-sulfate (PAPS, a molecule of AMP with a sulfate group attached to the 5-phosphate). Sulfotransferases cause the sulfation of the carbohydrate chain at specific sites. [Note An example of the synthesis of a sulfated glycosaminoglycan, chondroitin sulfate, is shown in Figure 14.11.] PAPS is also the sulfur donor in glycosphingolipid synthesis. [Note A defect in the sulfation process results in one of several autosomal recessive disorders that affect the proper development and maintenance of the skeletal system. This illustrates Ihe importance of the sulfation step.]... 

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