Glycosaminoglycan molecules

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. 

Molecules released by exocytosis fall into three categories (1) They can attach to the cell surface and become peripheral proteins, eg, antigens. (2) They can become part of the extracellular matrix, eg, collagen and glycosaminoglycans. (3) They can enter extracellular fluid and signal other cells. Insulin, parathyroid hormone, and the catecholamines are all packaged in gran-... 

Heparin is a carbohydrate-based (glycosaminoglycan) anticoagulant associated with many tissues, but mainly found stored intracellularly as granules in mast cells that line the endothelium of blood vessels. Upon release into the bloodstream, heparin binds to and thereby activates an additional plasma protein, namely antithrombin. The heparin-antithrombin complex then binds a number of activated clotting factors (including Ha, IXa, Xa, XIa and Xlla), thereby inactivating them. The heparin now disassociates from the complex and combines with another antithrombin molecule, thereby initiating another turn of this inhibitory cycle. 

Unfractionated heparin (UFH) is a heterogeneous mixture of sulfated glycosaminoglycans of variable lengths and pharmacologic properties. The molecular weight of these molecules ranges from 3,000 to 30,000 daltons (mean 15,000 daltons). 

Because of their large number of negative charges, these heteropolysaccharide chains tend to be extended in solution. They repel each other and are surrounded by a shell of water molecules. When brought together, they "slip" past each other, much as two magnets with the same polarity seem to slip past each other. This produces the "slippery" consistency of mucous secretions and synovial fluid. When a solution of glycosaminoglycans is compressed,... 

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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