After studying this chapter, you should be able to:
- Have a general appreciation of the importance of glycobiology and glycomics, and in particular of glycoproteins, in health and disease.
- Know the principal sugars found in glycoproteins.
- Be aware of the several major classes of glycoproteins (N-linked, O-linked, and GPI-linked).
- Understand the major features of the pathways of biosynthesis and degradation of O- and N-linked glycoproteins.
- Understand the importance of advanced glycation end-products in causing tissue damage in diabetes mellitus.
- Be able to indicate the involvement of glycoproteins in inflammation and in a host of conditions including I-cell disease, congenital disorders of glycation, paroxysmal nocturnal hemoglobinuria and cancer.
- Be familiar with the concept that many microorganisms, such as influenza virus, attach to cell surfaces via sugar chains.
Glycobiology is the study of the roles of sugars in health and disease. The glycome is the entire complement of sugars, whether free or present in more complex molecules, of an organism. Glycomics, an analogous term to genomics and proteomics, is the comprehensive study of glycomes, including genetic, physiologic, pathologic, and other aspects.
One major class of molecules included in the glycome is glycoproteins. These are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbones. It has been estimated that approximately 50% of eukaryotic proteins have sugars attached, so that glycosylation (enzymic attachment of sugars) is the most frequent posttranslational modification of proteins. Nonenzymic attachment of sugars to proteins can also occur, and is referred to as glycation. This process can have serious pathologic consequences (eg, in poorly controlled diabetes mellitus). Glycoproteins are one class of glycoconjugate or complex carbohydrate—equivalent terms used to denote molecules containing one or more carbohydrate chains covalently linked to protein (to form glycoproteins or proteoglycans) or lipid (to form glycolipids). (Proteoglycans are discussed in Chapter 48 and glycolipids in Chapter 15.) Almost all the plasma proteins of humans—with the notable exception of albumin—are glycoproteins. Many proteins of cellular membranes (Chapter 40) contain substantial amounts of carbohydrate. A number of the blood group substances are glycoproteins, whereas others are glycosphingolipids. Certain hormones (eg, chorionic gonadotropin) are glycoproteins. A major problem in cancer is metastasis, the phenomenon whereby cancer cells leave their tissue of origin (eg, the breast), migrate through the bloodstream to some distant site in the body (eg, the brain), and grow there in an unregulated manner, with catastrophic results for the affected individual. Many cancer researchers think that alterations in the structures of glycoproteins and other glycoconjugates on the surfaces of cancer cells are important in the phenomenon of metastasis.
Glycoproteins occur in most organisms, from bacteria to humans. Many viruses also contain glycoproteins, some of which have been much investigated, in part because they often play key roles in viral attachment to cells (eg, HIV-1 and influenza A virus). Numerous proteins with diverse functions are glycoproteins (Table 47–1); ...