# Lecture 17: Carbohydrates: Disaccharides and Polysaccharides
## Organic Chemistry II
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## Learning Objectives
By the end of this lecture, students will be able to:
1. Define glycosidic bonds and describe how they link monosaccharides
2. Draw and name common disaccharides (maltose, cellobiose, lactose, sucrose)
3. Distinguish between reducing and non-reducing disaccharides
4. Describe the structures and functions of starch, glycogen, and cellulose
5. Explain why humans can digest starch but not cellulose
6. Describe the roles of carbohydrates in cell recognition and blood group antigens
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## Lecture Content
### I. Glycosidic Bonds
A glycosidic bond is an acetal linkage that connects the anomeric carbon of one sugar to an oxygen on another sugar (or on a non-sugar molecule called an aglycon). The naming convention specifies whether the anomeric carbon has the alpha or beta configuration and identifies the carbon numbers involved. An alpha-1,4-glycosidic bond, for example, connects C1 of one sugar (in the alpha configuration) to the oxygen at C4 of the other.
Glycosidic bonds are formed by acid-catalyzed condensation of the anomeric hydroxyl with the hydroxyl of another sugar. They are cleaved by aqueous acid or by specific glycosidase enzymes. The enzyme specificity is crucial: alpha-glycosidases cleave alpha linkages but not beta ones, and vice versa. This selectivity has profound biological consequences.
### II. Disaccharides
Maltose (malt sugar) consists of two D-glucose units joined by an alpha-1,4-glycosidic bond. The anomeric carbon of the second glucose unit remains free as a hemiacetal, making maltose a reducing sugar capable of opening to the aldehyde form. Maltose is found in germinating grains and is produced by the enzymatic hydrolysis of starch by the enzyme maltase.
Cellobiose also consists of two D-glucose units, but they are joined by a beta-1,4-glycosidic bond. It too is a reducing sugar. Cellobiose is obtained by partial hydrolysis of cellulose, and the beta linkage gives it a fundamentally different three-dimensional shape compared to maltose.
Lactose (milk sugar) is composed of D-galactose and D-glucose joined by a beta-1,4-glycosidic bond, with galactose providing the anomeric carbon and glucose retaining a free anomeric hydroxyl. Lactose is a reducing sugar and is hydrolyzed by the enzyme lactase (beta-galactosidase). Lactose intolerance results from a deficiency of lactase, causing undigested lactose to be fermented by gut bacteria, producing gas and discomfort. Galactose and glucose are C4 epimers.
Sucrose (table sugar) is the most abundant disaccharide in nature. It consists of D-glucose and D-fructose joined by an alpha-1,2-glycosidic bond, meaning that the anomeric carbon of glucose (C1, in the alpha configuration) is linked to the anomeric carbon of fructose (C2, in the beta configuration). Because both anomeric carbons participate in the glycosidic bond, neither can open to the free carbonyl form, making sucrose a non-reducing sugar. Sucrose is hydrolyzed by the enzyme sucrase (invertase), and the resulting mixture of glucose and fructose is called "invert sugar" because the specific rotation changes sign upon hydrolysis.
Structural drawings of four disaccharides in Haworth projection. Panel A: Maltose showing two glucose units linked by an alpha-1,4 bond, with the free anomeric OH on the right-hand glucose highlighted and labeled as the reducing end. Panel B: Cellobiose showing two glucose units linked by a beta-1,4 bond. Panel C: Lactose showing galactose linked to glucose by a beta-1,4 bond. Panel D: Sucrose showing glucose and fructose linked through both anomeric carbons (alpha-1, beta-2 bond), with a note indicating no free anomeric carbon and therefore non-reducing.
### III. Polysaccharides: Starch
Starch is the primary storage polysaccharide in plants, found abundantly in potatoes, rice, wheat, and corn. It is composed entirely of D-glucose units and exists as a mixture of two components.
Amylose, which accounts for about 20 to 30 percent of starch, is an unbranched chain of D-glucose units linked exclusively by alpha-1,4-glycosidic bonds. Chains typically contain 200 to 1000 glucose units and adopt a helical conformation (a left-handed helix with approximately six glucose units per turn). Amylose gives a deep blue color with iodine because the I2/I- complex fits neatly inside the helix.
Amylopectin, comprising 70 to 80 percent of starch, is a branched polymer. Its backbone consists of alpha-1,4-glycosidic bonds, but every 24 to 30 glucose units, a branch point occurs through an alpha-1,6-glycosidic bond. Amylopectin molecules are much larger than amylose, containing up to a million glucose units, and give a red-violet color with iodine.
Digestion of starch begins in the mouth with salivary amylase (ptyalin) and continues in the small intestine with pancreatic amylase. These alpha-amylases are endoglycosidases that cleave alpha-1,4 bonds at random points along the chain, producing maltose and branched oligosaccharides called dextrins. Maltase and the debranching enzyme isomaltase complete the digestion, releasing free glucose.
### IV. Polysaccharides: Glycogen
Glycogen is the storage polysaccharide in animals, deposited primarily in the liver and skeletal muscle. Its structure resembles amylopectin but is more highly branched, with alpha-1,6 branch points occurring every 8 to 12 glucose units. Individual glycogen molecules can contain up to 10 million glucose units.
The extensive branching is functionally significant because it creates many non-reducing ends that are simultaneously accessible to degradative enzymes. Glycogen phosphorylase cleaves glucose units from these non-reducing ends, enabling rapid mobilization of glucose when energy is needed. The synthesis of glycogen (glycogenesis) is catalyzed by glycogen synthase, while its breakdown (glycogenolysis) is catalyzed by glycogen phosphorylase.
### V. Polysaccharides: Cellulose
Cellulose is the primary structural polysaccharide in plants and the most abundant organic compound on Earth. Like starch, it is composed entirely of D-glucose units, but the linkage is fundamentally different: cellulose uses beta-1,4-glycosidic bonds. This single difference in stereochemistry at the anomeric carbon has dramatic structural consequences.
The beta linkage forces each successive glucose unit to flip 180 degrees relative to its neighbor, producing a flat, ribbon-like chain rather than the helical coil of amylose. These flat chains engage in extensive intermolecular hydrogen bonding between parallel strands, assembling into strong, rigid microfibrils. Cellulose is insoluble in water and forms the major structural component of plant cell walls, wood, cotton, and paper. Typical cellulose chains contain 1000 to 15,000 glucose units.
Humans cannot digest cellulose because we lack cellulase, the beta-glucosidase enzyme that cleaves beta-1,4 bonds. Cellulose passes through the human digestive tract as dietary fiber. Ruminant animals such as cows and sheep can digest cellulose thanks to symbiotic bacteria and protozoa in their rumen that produce cellulase. Termites similarly rely on symbiotic microorganisms.
Structural comparison of amylose and cellulose. Top panel: Amylose with alpha-1,4 linkages showing the helical coiled conformation, with glucose units in the same orientation, and an inset showing the alpha-glycosidic bond geometry. Bottom panel: Cellulose with beta-1,4 linkages showing the flat, ribbon-like extended conformation, with alternating glucose units flipped 180 degrees, and an inset showing the beta-glycosidic bond geometry. Intermolecular hydrogen bonds between cellulose chains are depicted as dashed lines forming a sheet structure.
### VI. Other Important Polysaccharides
Chitin is the second most abundant polysaccharide, serving as the structural material in arthropod exoskeletons and fungal cell walls. It consists of N-acetylglucosamine units linked by beta-1,4-glycosidic bonds, giving it a structure similar to cellulose but with an N-acetylamino group at C2 in place of the hydroxyl.
Glycosaminoglycans (GAGs) are long, unbranched polysaccharides built from repeating disaccharide units. Examples include hyaluronic acid, chondroitin sulfate, and heparin. These molecules carry numerous negative charges from carboxylate and sulfate groups, causing them to attract water and form a gel-like matrix in connective tissues. Heparin serves as a clinically important anticoagulant.
Peptidoglycan (murein) is the structural polysaccharide of bacterial cell walls. Its sugar backbone alternates between N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) connected by beta-1,4 bonds, with short peptide chains cross-linking adjacent strands. Penicillin and other beta-lactam antibiotics kill bacteria by inhibiting the enzymes that form these peptide cross-links.
### VII. Carbohydrates in Cell Recognition
Glycoproteins are proteins with covalently attached carbohydrate chains that face the extracellular environment. They play essential roles in cell-cell recognition, immune responses, and blood type determination.
The ABO blood group system is determined by the terminal sugar residue on glycolipids and glycoproteins of red blood cell surfaces. Type O blood has the H antigen, which features a fucose residue attached to a galactose-N-acetylglucosamine core. Type A blood adds N-acetylgalactosamine to the terminal position of the H antigen. Type B blood adds galactose instead. Type AB has both modifications. Antibodies in the blood recognize these sugar epitopes, forming the basis of blood type compatibility and transfusion medicine.
Lectins are proteins that bind specific carbohydrate structures with high selectivity. They participate in cell adhesion, immune recognition, and the interactions between pathogens and their host cells.
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