Serglycin

Proteoglycans may be soluble and located in the extracellular matrix, as is the case for serglycin, versican, and the cartilage matrix proteoglycan, or they may be integral transmembrane proteins, such as syndecan. Both types of proteoglycan... 

Heparin is synthesized in connective-tissue type mast cells, as part of the serglycin proteoglycan. HS is produced by most mammalian (and many other) cells and is bound to a variety of core proteins, in particular syndecans, gly-picans, perlecan, and agrin. Following translation in the rough endoplasmic... 

There are quantitative differences in the chemical constitution of heparan sulfate and heparin polysaccharides, but qualitative differences in their biological location and core protein. " Heparin is biosynthesised only in connective tissue mast cells and attached only to a unique protein core (serglycin). The initial polysaccharide chains have a DP (dimer) of 25(T400, but can be cleaved subsequently to give an array of heparin polysaccharides. Heparan sulfate, by contrast, can be synthesised on an array of proteins in various cells, with two major subfamilies of heparan sulfate proteoglycans, the syndecans and glypi-cans, which carry fewer and shorter polysaccharide chains. 

A new block synthesis of peptides can be applied with 0-glycosylated derivatives, and in this way the 82-mer diptericin 70 has been made by methods involving the coupling of cysteine to a benzylthio ester. Solid phase methods were used to make serglycin glycopeptides e.g. 71. ... 

Heparin is predominandy produced by mast cells as part of a proteoglycan (PG), where the GAG chains are covalently attached (O-linked) to a serglycin core protein. After synthesis, the heparin chains are cleaved, and the so obtained disperse mixture of polysaccharides is stored in the cytoplasmic granules of the cells. HS—as well as CS and DS—is also found as O-glycosidic part of PGs, but they can be attached to a variety of different core proteins (e.g., syndecans and glypicans). Almost all mammahan cells biosynthesize such PGs, which can be found as part of cell membranes or as components of the extracellular matrix (Rabenstein, 2002 Silbert Sugumaran, 2002). 

Figure 2. A few common CS and DS proteoglycans. Decorin, aggrecan, syndecan-1, and serglycin are represented diagrammatically. Thicker solid lines represent core proteins, with a box toward the C-terminus of syndecan to indicate its transmembrane domain. Thinner solid lines indicate CS or DS chains, and dashed lines are HS chains. For serglycin, the GAG chains may be CS or HS. It is not shown, but aggrecan may also have KS chains, and most proteoglycans will have A-linked oligosaccharides and may have O-linked oligosaccharides.

Within the mast cell secretory granule, serglycin binds a large number of basic proteases (tryptases and chymases) and vasoactive amines, especially histamine, which are released upon degranulation of mast cells from a variety of stimuli, including injury, cytokines and immune reactions, especially those involved in IgE-dependent allergic responses (reviewed in [34]). 

The HS chains of serglycin are highly sulfated and rich in iduronic acid and, when processed by commercial means, yield the pharmaceutical product heparin. There is no qualitative difference between the HS chains of serglycin, sometimes referred to as heparin chains, and the HS chains on other HSPGs rather the structures represent a continuum, with the serglycin HS chain likely reflecting the lack of unmodified domains [35]. These differences presumably result from distinct isoforms of the biosynthetic enzymes. 

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