Diseases of Glycosaminoglycan and Proteoglycan Metabolism

Acidic polysaccharides with their high hydrodynamic volumes constitute one of the critical elements of most connective tissues. The major animal polysaccharides are linear repeats of a uronic acid-amino sugar disaccharide. The most detailed picture of metabolic processes involved with this class of macromolecules has come from studies on a group of human genetic disorders usually referred to as the mucopolysaccharidoses. Higher-order structures form outside the cell by way of nonconvalent interactions. The pathway is largely based on structures of cartilaginous connective tissue and the assembly of glycosylated excretory proteins. The highly hydrated proteoglycans (PG) aggregates are held in a compressed conformation by a mesh-work of fibrous proteins such as collagen and elastin. The fine structure of fibrous proteins and PG aggregates are highly interdependent, each interacting with the other in a variety of specific and nonspecific ways. The breakdown of matrix structures appears to be initiated by glycosidases and pro-teases acting pretty much at random throughout the meshwork.