After studying this chapter, you should be able to:
Explain the importance of glycoproteins in health and disease.
Describe the principal sugars found in glycoproteins.
Describe the major classes of glycoproteins (N-linked, O-linked, and GPI-linked).
Describe the major features of the pathways of biosynthesis and degradation of glycoproteins.
Explain how many microorganisms, such as influenza virus, attach to cell surfaces via sugar chains.
The glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently bound to amino acids; glycosylation (the enzymic attachment of sugars) is the most frequent posttranslational modification of proteins. Many proteins also undergo reversible glycosylation with a single sugar (N-acetylglucosamine) bound to a serine or threonine residue that is also a site for reversible phosphorylation. This is an important mechanism of metabolic regulation. 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—molecules containing one or more carbohydrate chains covalently linked to protein (to form glycoproteins or proteoglycans, see Chapter 50) or lipid (to form glycolipids, see Chapter 21). Almost all plasma proteins, and many peptide hormones, are glycoproteins, as are a number of blood group substances (others are glycosphingolipids). Many cell membrane proteins (see Chapter 40) contain substantial amounts of carbohydrate, and many are anchored to the lipid bilayer by a glycan chain. Evidence is accumulating that alterations in the structures of glycoproteins and other glycoconjugates on the surface of cancer cells are important in metastasis.
GLYCOPROTEINS OCCUR WIDELY & PERFORM NUMEROUS FUNCTIONS
Glycoproteins occur in most organisms, from bacteria to human beings. Many viruses also contain glycoproteins, some of which play key roles in viral attachment to host cells. The glycoproteins have a wide range of functions (Table 46–1); their carbohydrate content ranges from 1 to over 85% by weight. The glycan structures of glycoproteins change in response to signals involved in cell differentiation, normal physiology, and neoplastic transformation. This is the result of different expression patterns of glycosyltransferases. Table 46–2 lists some of the major functions of the glycan chains of glycoproteins.
TABLE 46–1Some Functions Served by Glycoproteins ||Download (.pdf) TABLE 46–1 Some Functions Served by Glycoproteins
|Function ||Glycoproteins |
|Structural molecule ||Collagens |
|Lubricant and protective agent ||Mucins |
|Transport molecule ||Transferrin, ceruloplasmin |
|Immunological molecule ||Immunoglobulins, histocompatibility antigens |
|Hormone ||Chorionic gonadotropin, thyroid-stimulating hormone (TSH) |
|Enzyme ||Various, eg, alkaline phosphatase |
|Cell attachment–recognition site ||Various proteins involved in cell–cell (eg, sperm-oocyte), virus-cell, bacterium-cell, and hormone-cell interactions |
|Antifreeze ||Plasma proteins of cold-water fish |
|Interact with specific carbohydrates ||Lectins, selectins (cell adhesion lectins), antibodies |
|Receptor ||Cell surface proteins involved in hormone and drug action |
|Regulate folding ...|