Other Glycoproteins

Lipoproteins bind a small amount of certain drugs (imipramine, amitriptyline, nortriptyline, phenytoin, and quinidine), which usually bind to alpha,-acid glycoprotein. 

The binding sites of the protein are not unlimited and are subject to saturation. When this occurs, toxicity may develop following further drug administration, because the later portion of the drug remains free. Consistent with this view is the observation that toxic manifestations of drugs are quite frequent and considerably higher in individuals suffering from hypoalbuminemia, or altered plasma and tissue protein concentrations, or both. 

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All of the glycoproteins and glycopeptides thus far mentioned probably contain their carbohydrate as moieties whose size does not exceed 15 sugar residues this point will be discussed later (see p. 447). Other glycoproteins are known in which at least some of... 

The presence of D-xylose in several other glycoproteins,38 including an alpha-amylase (see p. 442) and pineapple-stem bromelain134 has been reported, but its mode of attachment is not yet known. 

Another factor influencing nonspecific tissue distribution is the carbohydrate portion of the IgG molecule, which is attached to the therapeutic protein via an N-linked glycan in the constant domain (Fc). Loss of terminal sialylated residues on the carbohydrate of IgG exposes galactose and promotes receptor-mediated binding of IgG to hepatocytes. Consequently this results in an increase in nonspecific distribution to the liver. Details of desialyation of IgG and its consequences are discussed in Chapter 10. Other glycoproteins may exert similar mechanisms of nonspecific distribution. 

If all the sugar residues of the glycophorin molecules in an erythrocyte were spread over the surface of the cell they could cover approximately one-fifth of its surface in a loose network. However, it is more likely that they form bushy projections of a more localized sort. These oligosaccharides not only act as immunological determinants but also serve as receptors for influenza viruses. Other glycoproteins related to glycophorin A occur in smaller amounts.244... 

In the MFGM of human milk, mucin is associated with two other glycoproteins, butyrophilin and lactadherin. Yolken et al. (1992) found that a non-immunological fraction of human milk inhibited the replication of rotaviruses in tissue culture, and prevented the development of gastroenteritis in an animal model. Further characterization indicated that virus bound to mucin and to the associated 46 kD protein (identified as lactadherin). The biological functions of lactadherin may be related to its ability to interact physically with a wide variety of molecules. 

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