Polysaccharide chains are too stiff to fold into compact globular structures, and they are strongly hydrophilic. Thus, GAGs tend to adopt highly extended conformations that occupy a huge volume relative to their mass (Figure 19–33), and they form hydrated gels even at very low concentrations. The weight of GAGs in connective tissue is usually less than 10% of the weight of proteins, but GAG chains fill most of the extracellular space. Their high density of negative charges attracts a cloud of cations, especially Na+, that are osmotically active, causing large amounts of water to be sucked into the matrix. This creates a swelling pressure, or turgor, that enables the matrix to withstand compressive forces (in contrast to collagen fibrils, which resist stretching forces). The cartilage matrix that lines the knee joint, for example, can support pressures of hundreds of atmospheres in this way.
Defects in the production of GAGs can affect many different body systems. In one rare human genetic disease, for example, there is a severe deficiency in the synthesis of dermatan sulfate disaccharide. The affected individuals have a short stature, a prematurely aged appearance, and generalized defects in their skin, joints, muscles, and bones.
Figure 19–31 The comparative shapes and sizes of some of the major extracellular matrix macromolecules.
protein is shown in green, and glycosaminoglycan (GaG) in red.
Figure 19–32 The repeating disaccharide sequence of a heparan sulfate glycosaminoglycan (GAG) chain. these chains can consist of as many as 200 disaccharide units, but are typically less than half that size. there is a high density of negative charges along the chain due to the presence of both carboxyl and sulfate groups. the molecule is shown here with its maximal number of sulfate groups. In vivo, the proportion of sulfated and nonsulfated groups is variable. heparin typically has >70% sulfation, while heparan sulfate has <50%.
hyaluronan acts as a Space Filler During tissue Morphogenesis and repair
Hyaluronan (also called hyaluronic acid or hyaluronate) is the simplest of the GAGs (Figure 19–34). It consists of a regular repeating sequence of up to 25,000 disaccharide units, is found in variable amounts in all tissues and fluids in adult animals, and is especially abundant in early embryos. Hyaluronan is not a typical GAG because it contains no sulfated sugars, all its disaccharide units are identical, its chain length is enormous, and it is not generally linked covalently to any core protein. Moreover, whereas other GAGs are synthesized inside the cell and released by exocytosis, hyaluronan is spun out directly from the cell surface by an enzyme complex embedded in the plasma membrane.
Hyaluronan is thought to have a role in resisting compressive forces in tissues and joints. It is also important as a space filler during embryonic development, where it can be used to force a change in the shape of a structure, as a small quantity expands with water to occupy a large volume. Hyaluronan synthesized locally from the basal side of an epithelium can deform the epithelium by creating a cell-free space beneath it, into which cells subsequently migrate. In the developing heart, for example, hyaluronan synthesis helps in this way to drive formation of the valves and septa that separate the heart’s chambers. Similar processes occur in several other organs. When cell migration ends, the excess hyaluronan is generally degraded by the enzyme hyaluronidase. Hyaluronan is also produced in large quantities during wound healing, and it is an important constituent of joint fluid, in which it serves as a lubricant.
proteoglycans are Composed of GaG Chains Covalently Linked to a Core protein