Glycoproteins - Hughes, R. 1985

Structure
Structure of O-glycans

In addition to the aforementioned points regarding Collagen O-glycans, several Characteristic Properties of glycans attached via glycosidic bonds to amino acid hydroxyl groups warrant further Structure/133.html">Discussion.

Class="center">2.5.1. Secrets of the Glycoprotein Nature (Mucins)

Glycoproteins containing large amounts of O-linked glycans are familiar to anyone who has seen the slimy trail left by a snail crawling across a dry path, or who has tasted bird's nest soup in a Chinese restaurant. These and similar glycoproteins are often called mucins or mucoids due to their exceptionally high viscosity and gel-like appearance. The German chemist Hoppe-Seyler used the rather unflattering term Schleimstoff, i.e., mucus, to designate them. These substances are rather unpleasant in appearance and inconvenient to work with, particularly when attempting chemical and physical analyses. Nevertheless, it should be remembered that mucins perform vital biological Functions. It is crucial for higher organisms (both vertebrates and invertebrates) that the cavities of the respiratory, digestive, and urogenital tracts are lined with a layer of Cells secreting viscous glycoproteins. Examples of such secretions include saliva (which, incidentally, is the main ingredient in bird's nest soup), bronchial and intestinal secretions, seminal fluid, and cervical mucus. All of these can act as lubricants, for instance in the digestive tract. Furthermore, the thick viscous layer protects underlying Tissues from mechanical and chemical damage (such as from digestive juices).

Secretory glycoproteins have been intensively studied for many years. This is due both to their important biological role and to their association with severe disorders, such as cystic fibrosis. The carbohydrate composition is best understood in salivary gland secretions, particularly glycoproteins from the submandibular gland. Two decades ago, Alfred Gottschalk, working first in Australia and later in West Germany, conducted detailed studies on The structure of the simplest substance found in sheep glands. In this glycoprotein, a disaccharide consisting of N-acetylneuraminic acid and N-acetylgalactosamine residues is attached to numerous Serine and Threonine residues of the polypeptide chain (Fig. 2.14). It turned out that one in every six amino acid residues is a glycosylated serine or threonine, with about 200 such residues per polypeptide chain. The third most common amino acid in submandibular gland glycoproteins is Proline, making the glycosylated regions exceptionally rich in it. The protein itself resembles a comb in structure: short carbohydrate chains, like Teeth, project from a rigid, proline-rich polypeptide backbone. These comb-like structures, linked by disulfide bridges between protein globules, form large glycoprotein molecules with unique viscous properties [4]. In the submandibular glycoproteins of other animal species, many other oligosaccharide chains are attached to the Polypeptides in addition to the Disaccharides described above (Fig. 2.14). For example, the well-characterized porcine submandibular secretion contains the neutral disaccharide galß1→3gaINAc, along with its sialylated forms. Of particular interest are the fucose-containing chains of the porcine glycoprotein. Such chains are easily detected because they also occur in human secretions, such as the Blood group H antigen. The addition of an N-acetylgalactosamine residue converts the H antigenic determinant into the blood group A antigen, a structure also found in porcine submandibular glycoproteins (Fig. 2.14).

Fig. 2.14. Structure of O-glycans from submandibular gland (SMG) secretory Proteins. The N-acetylgalactosamine residue is linked to serine (or threonine); R represents a serine or threonine residue of the polypeptide chain.

Very little is known about the mucous secretions of The Stomach and intestine, despite the relative ease of obtaining them. This is because such secretions represent complex mixtures of numerous glycoproteins that are extremely difficult to separate. Figure 2.15 illustrates the structure of some O-glycans recently identified [16] in the rat colon. Several characteristic features deserve mention, most notably a novel type of linkage: N-acetylglucosaminyl (ß1→3) N-acetylgalactosamine. The first of these residues serves as a site for chain elongation, converting it into a highly complex sequence. The longest chain terminates in a region characteristic of the A determinant (compare with the chain responsible for A-activity found in porcine submandibular secretions; Fig. 2.14).

Fig. 2.15. Structure of O-glycans from rat colonic glycoproteins, where R represents a serine or threonine residue of the polypeptide chain [16].