The most important storage polysaccharides are starch in plant cells and glycogen in animal cells. Both polysaccharides occur intracellularly as large clusters or granules. Starch and glycogen molecules are heavily hydrated, because they have many exposed hydroxyl groups available to hydrogen-bond with water. Most plant cells have the ability to form starch, and starch storage is especially abundant in tubers (underground stems), such as potatoes, and in seeds.

Starch contains two types of glucose polymer, amylose and amylopectin (Fig. 7-13). Amylose consists of long, unbranched chains of d-glucose residues connected by linkages (as in maltose). Such chains vary in molecular weight from a few thousand to more than a million. Amylopectin is even larger ( up to 200 million) but unlike amylose is highly branched. The glycosidic linkages joining successive glucose residues in amylopectin chains are ; the branch points (occurring every 24 to 30 residues) are linkages.

Glycogen is the main storage polysaccharide of animal cells. Like amylopectin, glycogen is a polymer of -linked glucose subunits, with -linked branches, but glycogen is more extensively branched (on average, a branch every 8 to 12 residues) and more compact than starch. Glycogen is especially abundant in the liver, where it may constitute as much as 7% of the wet weight; it is also present in skeletal muscle. In hepatocytes, glycogen is found in large α granules (see Fig. 15-1), which are clusters of smaller β granules, each of which is a single, highly branched glycogen molecule with an average molecular weight of several million. The large α glycogen granules also contain, in tightly bound form, the enzymes responsible for the synthesis and degradation of glycogen (see Fig. 15-16).

Because each branch of glycogen ends with a nonreducing sugar unit, a glycogen molecule with n branches has nonreducing ends, but only one reducing end. When glycogen is used as an energy source, glucose units are removed one at a time from the nonreducing ends. Degradative enzymes that act only at nonreducing ends can work simultaneously on the many branches, speeding the conversion of the polymer to monosaccharides.

Why not store glucose in its monomeric form? Hepatocytes in the fed state store glycogen equivalent to a glucose concentration of 0.4 m. The actual concentration of glycogen, which contributes little to the osmolarity of the cytosol, is about 0.01 μm. If the cytosol contained 0.4 m glucose, the osmolarity would be threateningly elevated, leading to osmotic entry of water that might rupture the cell (see Fig. 2-12).

Cellulose, a tough, fibrous, water-insoluble substance, is found in the cell walls of plants, particularly in stalks, stems, trunks, and all the woody portions of the plant body. Cellulose constitutes much of the mass of wood, and cotton is almost pure cellulose. Like amylose, the cellulose molecule is a linear, unbranched homopolysaccharide, consisting of 10,000 to 15,000 d-glucose units. But there is a very important difference: in cellulose the glucose residues have the β configuration (Fig. 7-14), whereas in amylose the glucose is in the α configuration. The glucose residues in cellulose are linked by glycosidic bonds, in contrast to the bonds of amylose. This difference causes individual molecules of cellulose and amylose to fold differently in space, giving them very different macroscopic structures and physical properties.

The tough, fibrous nature of cellulose makes it useful in such commercial products as cardboard and insulation material, and it is a major constituent of cotton and linen fabrics. Cellulose is also the starting material for the commercial production of cellophane, rayon, and lyocell.

Chitin is a linear homopolysaccharide composed of N-acetylglucosamine residues in linkage (Fig. 7-15). The only chemical difference from cellulose is the replacement of the hydroxyl group at C-2 with an acetylated amino group, which makes chitin more hydrophobic and water-resistant than cellulose. Chitin forms extended fibers similar to those of cellulose, and like cellulose cannot be digested by vertebrates. Chitin is the principal component of the hard exoskeletons of nearly a million species of arthropods — insects, lobsters, and crabs, for example — and is probably the second most abundant polysaccharide, next to cellulose, in nature; an estimated 1 billion tons of chitin are produced in the biosphere each year.

The folding of polysaccharides in three dimensions follows the same principles as those governing polypeptide structure: subunits with a more-or-less rigid structure dictated by covalent bonds form three-dimensional macromolecular structures that are stabilized by weak interactions within or between molecules, such as hydrogen bonds, interactions due to the hydrophobic effect, van der Waals interactions, and, for polymers with charged subunits, electrostatic interactions. Because polysaccharides have so many hydroxyl groups, hydrogen bonding has an especially important influence on their structure. Glycogen, starch, cellulose, and chitin are composed of pyranoside (six-membered ring) subunits, as are the oligosaccharides of glycoproteins and glycolipids, to be discussed later. Such molecules can be represented as a series of rigid pyranose rings connected by an oxygen atom bridging two carbon atoms (the glycosidic bond). There is, in principle, free rotation about both COO bonds linking the residues, but as in polypeptides (see Figs 4-2, 4-8), rotation about each bond is limited by steric hindrance by substituents. The three-dimensional structures of these molecules can be described in terms of the dihedral angles, ϕ and ψ, about the glycosidic bond (Fig. 7-16). The bulkiness of the pyranose ring and its substituents, along with electronic effects at the anomeric carbon, place constraints on the angles ϕ and ψ; thus, certain conformations are much more stable than others.

The most stable three-dimensional structure for the -linked chains of starch and glycogen is a tightly coiled helix (Fig. 7-17), stabilized by interchain hydrogen bonds. The average plane of each residue along the amylose chain forms a angle with the average plane of the preceding residue, so the helical structure has six residues per turn. For amylose, the core of the helix is of precisely the right dimensions to accommodate iodine as complex ions . This interaction gives an intensely blue product, making it a common qualitative test for amylose.

For cellulose, the most stable conformation is that in which each chair is turned relative to its neighbors, yielding a straight, extended chain. All —OH groups are available for hydrogen bonding with neighboring chains. With several chains lying side by side, a stabilizing network of interchain and intrachain hydrogen bonds produces straight, stable supramolecular fibers of great tensile strength (Fig. 7-18). This property of cellulose has made it useful to civilizations for millennia. Many manufactured products, including papyrus, paper, cardboard, rayon, insulating tiles, and a variety of other useful materials, are derived from cellulose. The water content of these materials is low because extensive interchain hydrogen bonding between cellulose molecules satisfies their capacity for hydrogen-bond formation.

The rigid component of bacterial cell walls (peptidoglycan) is a heteropolymer of alternating -linked N-acetylglucosamine and N-acetylmuramic acid residues (see Fig. 6-32). The linear polymers lie side by side in the cell wall, cross-linked by short peptides, the exact structure of which depends on the bacterial species. The peptide cross-links weld the polysaccharide chains into a strong sheath (peptidoglycan) that envelops the entire cell and prevents cellular swelling and lysis due to the osmotic entry of water.

The enzyme lysozyme kills bacteria by hydrolyzing the glycosidic bond between N-acetylglucosamine and N-acetylmuramic acid. The enzyme is found in human tears, where it is presumably a defense against bacterial infections of the eye, and in hen’s eggs, where it prevents bacterial infection of the developing embryo. Penicillin and related antibiotics kill bacteria by preventing synthesis of the peptidoglycan cross-links, leaving the cell wall too weak to resist osmotic lysis (p. 211).

The extracellular space in the tissues of multicellular animals is filled with a gel-like material, the extracellular matrix (ECM), which holds the cells together and provides a porous pathway for the diffusion of nutrients and oxygen to individual cells. The ECM is composed of an interlocking meshwork of heteropolysaccharides (also called ground substance) and fibrous proteins such as fibrillar collagens, elastins, and fibronectins. The basement membrane is a specialized ECM that underlies epithelial cells; it consists of specialized collagens, laminins, and heteropolysaccharides.

These heteropolysaccharides, the glycosaminoglycans, are a family of linear polymers composed of repeating disaccharide units (Fig. 7-19). They are unique to animals and bacteria and are not found in plants. One of the two monosaccharides is always either N-acetylglucosamine or N-acetylgalactosamine; the other is in most cases a uronic acid, usually d-glucuronic or l-iduronic acid. Some glycosaminoglycans contain esterified sulfate groups. The combination of sulfate groups and the carboxylate groups of the uronic acid residues gives glycosaminoglycans a very high density of negative charge. To minimize the repulsive forces among neighboring charged groups, these molecules assume an extended conformation in solution, forming a rodlike helix in which the negatively charged carboxylate groups occur on alternate sides of the helix (as shown for heparin in Fig. 7-19). The extended rod form also provides maximum separation between the negatively charged sulfate groups. The specific patterns of sulfated and nonsulfated sugar residues in glycosaminoglycans allow specific recognition by a variety of protein ligands that bind electrostatically to these molecules. The sulfated glycosaminoglycans are attached to extracellular proteins to form proteoglycans (Section 7.3).

The glycosaminoglycan hyaluronan (hyaluronic acid) contains alternating residues of d-glucuronic acid and N-acetylglucosamine (Fig. 7-19). With up to 50,000 repeats of the basic disaccharide unit, hyaluronan has a molecular weight of several million; it forms clear, highly viscous, noncompressible solutions that serve as lubricants in the synovial fluid of joints and give the vitreous humor of the vertebrate eye its jellylike consistency (the Greek hyalos means “glass”; hyaluronan can have a glassy or translucent appearance). Hyaluronan is also a component of the ECM of cartilage and tendons, to which it contributes tensile strength and elasticity as a result of its strong noncovalent interactions with other components of the matrix. Hyaluronidase, an enzyme secreted by some pathogenic bacteria, can hydrolyze the glycosidic linkages of hyaluronan, rendering tissues more susceptible to bacterial invasion. In many animal species, a similar enzyme in sperm hydrolyzes the outer glycosaminoglycan coat around an ovum, allowing sperm penetration.

Other glycosaminoglycans differ from hyaluronan in three respects: they are generally much shorter polymers, they are covalently linked to specific proteins (proteoglycans), and one or both monomeric units differ from those of hyaluronan. Chondroitin sulfate (Greek chondros, “cartilage”) contributes to the tensile strength of cartilage, tendons, ligaments, heart valves, and the walls of the aorta. Dermatan sulfate (Greek derma, “skin”) contributes to the pliability of skin and is also present in blood vessels and heart valves. In this polymer, many of the glucuronate residues present in chondroitin sulfate are replaced by their C-5 epimer, l-iduronate (IdoA).

Keratan sulfates (Greek keras, “horn”) have no uronic acid, and their sulfate content is variable. They are present in cornea, cartilage, bone, and a variety of horny structures formed from dead cells: horn, hair, hoofs, nails, and claws. Heparan sulfate (Greek hēpar, “liver”; it was originally isolated from dog liver) contains variable, nonrandom arrangements of sulfated and nonsulfated sugars. The exact sequence of sulfated residues gives the molecule the ability to interact specifically with a large number of proteins, including growth factors and ECM components, as well as various enzymes and factors present in plasma. Heparin is a highly sulfated, intracellular form of heparan sulfate produced primarily by mast cells (a type of leukocyte, or immune cell). Its physiological role is not yet clear, but purified heparin is used as a therapeutic agent to inhibit coagulation of blood through its capacity to bind the protease inhibitor antithrombin (see Fig. 7-24).

Table 7-2 summarizes the composition, properties, roles, and occurrence of the polysaccharides described in Section 7.2.

TABLE 7-2 Structures and Roles of Some Polysaccharides

Polymer	Typea	Repeating unitb	Size (number of monosaccharide units)	Roles/significance
Starch				Energy storage: in plants
Amylose	Homo-	, linear	50–5,000
Amylopectin	Homo-	, with branches every 24–30 residues	Up to
Glycogen	Homo-	, with branches every 8–12 residues	Up to 50,000	Energy storage: in bacteria and animal cells
Cellulose	Homo-		Up to 15,000	Structural: in plants, gives rigidity and strength to cell walls
Chitin	Homo-	NAc	Very large	Structural: in insects, spiders, crustaceans, gives rigidity and strength to exoskeletons
Dextran	Homo-	, with branches	Wide range	Structural: in bacteria, extracellular adhesive
Peptidoglycan	Hetero-; peptides attached	4)Mur2Ac GlcNAc	Very large	Structural: in bacteria, gives rigidity and strength to cell envelope
Hyaluronan (a glycosaminoglycan)	Hetero-; acidic	4)GlcA GlcNAc	Up to 100,000	Structural: in vertebrates, extracellular matrix of skin and connective tissue; viscosity and lubrication in joints
aEach polymer is classified as a homopolysaccharide (homo-) or heteropolysaccharide (hetero-). bThe abbreviated names for the peptidoglycan, agarose, and hyaluronan repeating units indicate that the polymer contains repeats of this disaccharide unit. For example, in peptidoglycan, the GlcNAc of one disaccharide unit is -linked to the first residue of the next disaccharide unit.