Glycoproteins - Hughes R. 1985

Introduction

Glycoproteins are Proteins in which oligosaccharide chains are attached to specific amino acid residues. Glycoproteins have been known for quite some time, and it is assumed that these proteins perform vital biological Functions [1–3]. The author hopes that after reading this book, the reader will be convinced of the validity of this statement.

The term "oligosaccharide" generally refers to a carbohydrate polymer composed of 2–10 monosaccharide units. A vast diversity of Monosaccharides exists in nature. The most common residue is D-glucose, three formulas of which are shown in Fig. 1.1. Monosaccharides vary in the length of their carbon chain, the number of hydroxyl or other equivalent groups (such as amino groups), and the spatial arrangement of hydroxyl groups and hydrogen atoms relative to the central axis. The Structure of an open six-carbon chain (Fig. 1.1) is merely a theoretical formula. In reality, monosaccharides exist exclusively as cyclic structures with 5 or 6 atoms in the ring, one of which is oxygen. Each monosaccharide typically occurs in only one specific cyclic form. For example, glucose exists as a six-membered cyclic pyranose form (Fig. 1.1), and in solution, its molecule adopts a preferred conformation known as the chair conformation (Fig. 1.1). As for the conformation of monosaccharide residues within glycoprotein molecules, much remains unclear. It should be noted, however, that the carbohydrate chains of glycoproteins possess a distinct three-dimensional structure, which is critical for fully elucidating the structure, METABOLISM, and function of these molecules [4]. In oligosaccharide chains, cyclic monosaccharides are linked to one another by covalent bonds.

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Fig. 1.1. Structural formulas of glucose.

Fig. 1.2. Structure of cyclic monosaccharides that make up the Oligosaccharides of glycoproteins. Hydrogen atoms are omitted for simplicity. The structure of neuraminic acids is shown in Fig. 2.3. The formation of (methyl) glucoside is illustrated using ß-D-glucopyranose as an example.

They are formed via the reaction of the hydroxyl group at C-1 with any hydroxyl group (other than the one at C-1) of a second monosaccharide, accompanied by the release of a Water molecule. This reaction is entirely analogous to the formation of a glycoside, such as methyl glycoside, and can be repeated involving any number of monosaccharides. The configuration at C-1 can vary, leading to the formation of either a- or ß-glycosidic bonds.

As will be shown later, the sizes of the carbohydrate chain in glycoproteins range from a disaccharide unit to highly complex structures containing 18 or even more monosaccharides. Strictly speaking, long carbohydrate chains should be referred to as Polysaccharides or glycans. The latter term is used very frequently; for example, one may speak of "Ovalbumin glycans." The molecules of certain proteins, such as Collagen and submandibular gland secretory proteins, contain only disaccharide units, whereas the carbohydrate chains or glycans of other glycoproteins are built from several monosaccharides and sometimes include up to seven different residues (Table 1.1). Glycans have a highly branched structure resembling a tree with a relatively rigid trunk and several branches that can exhibit high conformational flexibility. Most importantly, however, is the structural complexity of long glycoprotein glycans: their structure lacks any discernible periodicity. The structure of "true" (proper) polysaccharides, such as Cellulose, differs markedly from that of glycoprotein glycans. Typically, they consist of a limited set of different monosaccharides (often just a single monosaccharide; for example, only glucose in cellulose), featuring a defined repeating sequence of monosaccharides linked by characteristic glycosidic bonds, such as ß1→4 in cellulose. Such glycans are usually much longer than glycoprotein glycans. Nevertheless, this rather artificial distinction between true polysaccharides and glycoprotein carbohydrate chains is becoming obsolete. Above all, it has become clear that compounds previously regarded as "true" polysaccharides (e.g., starch, Glycogen, or heparin) with a typical repeating structure are synthesized on protein molecules; in other words, they begin their lifecycle as part of glycoproteins. Other representatives of this type of compound are the acidic polysaccharides of Connective Tissues, such as chondroitin sulfates, dermatan sulfate, and heparan sulfate. All these polysaccharides are tightly bound to protein and should be considered a special type of glycoprotein. They are commonly referred to as Proteoglycans, and these Connective Tissue substances will be designated as such below. Finally, for completeness, it should be mentioned that oligosaccharides similar to those found in glycoproteins can also be linked to a lipid such as ceramide. A detailed Description of the properties of such Glycolipids is not provided here, but it must be noted that these specific glycolipids are crucial components of Cell membranes. The function and metabolism of ceramide-linked sugars are often analogous to those of glycoprotein oligosaccharides. This similarity will be discussed in the relevant sections of this book.

Table 1.1. Glycoproteins, proteoglycans, and glycolipids

¹ To designate the corresponding monosaccharides, the following Abbreviations will be used below: glucose (glc, G), mannose (man, M), fucose (fuc, F), galactose (gal, Ga), N-acetylglucosamine (glcNAc, Gn), N-acetylgalactosamine (galNAc, Gan), N-acetylneuraminic acid (neuNAc, Sa,N).

² Always N-acylated.

All three classes of complex CARBOHYDRATES—glycoproteins, proteoglycans, and glycolipids (Table 1.1)—are sometimes collectively referred to by the term Glycoconjugates.

To denote complex carbohydrate sequences of glycans in this book, an abbreviated nomenclature is adopted. First, the monosaccharide residues of glycoproteins under Discussion are always in the pyranose form and, with the exception of L-fucose, in the D-configuration (Fig. 1.2). Second, although both a- and ß-forms commonly occur in glycans, There is a certain structural uniformity, and in some cases, the anomeric configuration of monosaccharide units may be omitted without loss of clarity. The abbreviated designations of monosaccharides used in the book are given in the footnote to Table 1.1.