Premed · Premed · Biochemistry
Lecture 10: Carbohydrate Chemistry and Structure
Biochemistry
Learning Objectives
By the end of this lecture, students will be able to:
- Classify carbohydrates as monosaccharides, disaccharides, oligosaccharides, and polysaccharides
- Describe the stereochemistry of monosaccharides (D/L, alpha/beta anomers)
- Draw Fischer and Haworth projections and convert between them
- Explain glycosidic bond formation and identify common disaccharides
- Describe the structure and function of major polysaccharides (glycogen, starch, cellulose)
- Explain the biological roles of glycoproteins and proteoglycans
Lecture Content
I. Introduction to Carbohydrates
Carbohydrates follow the general formula (CH2O)n -- hence the name "hydrates of carbon." They are classified by their functional group as aldoses (containing an aldehyde) or ketoses (containing a ketone), and by their number of carbons: trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), and heptoses (7C). These naming systems are combined to give precise descriptions: glucose is an aldohexose, fructose is a ketohexose, and ribose is an aldopentose.
II. Monosaccharide Stereochemistry
All monosaccharides except dihydroxyacetone have at least one chiral center. The D and L designation is based on the configuration of the highest-numbered chiral center, compared to D- and L-glyceraldehyde. In a Fischer projection, D-sugars have the hydroxyl on the highest-numbered chiral center pointing to the right. Most biologically relevant sugars are D-sugars.
The total number of stereoisomers equals 2^n, where n is the number of chiral centers. D-glucose, an aldohexose with 4 chiral centers, has 16 stereoisomers (8 D-forms and 8 L-forms). Epimers are sugars that differ in configuration at only one chiral center: D-glucose and D-mannose are epimers at C-2, while D-glucose and D-galactose are epimers at C-4. Enantiomers are complete mirror images, such as D-glucose and L-glucose.
III. Cyclization and Anomers
In solution, monosaccharides with five or more carbons cyclize through intramolecular hemiacetal or hemiketal formation. Aldohexoses like glucose form six-membered pyranose rings when the C-1 aldehyde reacts with the C-5 hydroxyl. Ketohexoses like fructose form five-membered furanose rings when the C-2 keto group reacts with the C-5 hydroxyl.
Cyclization creates a new chiral center at the anomeric carbon (C-1 for aldoses, C-2 for ketoses). The alpha anomer has the hydroxyl on the anomeric carbon in the axial position (pointing down in the Haworth projection), while the beta anomer has it in the equatorial position (pointing up). Mutarotation is the interconversion of alpha and beta anomers in solution through the open-chain form. At equilibrium, D-glucose is approximately 36% alpha and 64% beta, with the beta form being more stable because all its hydroxyls are equatorial.
<image>A figure showing the cyclization of D-glucose. Panel A: Fischer projection of open-chain D-glucose with all carbons and hydroxyls labeled. Panel B: The cyclization reaction showing the C-1 aldehyde attacking the C-5 hydroxyl to form a six-membered pyranose ring, with both alpha and beta anomers drawn as Haworth projections. The anomeric carbon (C-1) is highlighted, with the hydroxyl group pointing down in the alpha form and up in the beta form. Panel C: Chair conformations of alpha-D-glucopyranose and beta-D-glucopyranose, showing that all hydroxyls in the beta form are equatorial. Panel D: A diagram showing mutarotation — the equilibrium between alpha, open-chain, and beta forms with percentages at equilibrium.</image>
IV. Important Monosaccharides
D-Glucose is the most abundant monosaccharide, serving as the primary energy source and the principal sugar in blood. D-Galactose, an epimer of glucose at C-4, is a component of lactose and brain glycolipids. D-Mannose, an epimer of glucose at C-2, is common in glycoproteins. D-Fructose is a ketohexose found in fruits, honey, and semen and is the sweetest natural sugar. D-Ribose is an aldopentose that forms part of RNA, ATP, NAD+, FAD, and CoA. D-Deoxyribose (2-deoxyribose) is the sugar component of DNA, lacking the 2'-hydroxyl.
Several sugar derivatives are biologically important. Sugar acids result from oxidation of the aldehyde (aldonic acids) or the terminal hydroxyl (uronic acids, such as glucuronic acid). Sugar alcohols result from reduction of the carbonyl (sorbitol from glucose, ribitol from ribose). Amino sugars have an amino group replacing a hydroxyl (glucosamine, galactosamine), and these are often N-acetylated to form N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc). N-acetylneuraminic acid (sialic acid) is a 9-carbon sugar important in cell surface glycoproteins.
V. Disaccharides and the Glycosidic Bond
Disaccharides are formed by a glycosidic bond between the anomeric carbon of one sugar and a hydroxyl of another through a condensation reaction that releases water. They are named by the configuration (alpha or beta), the carbons involved, and the component sugars.
Maltose (Glc alpha-1,4 Glc) consists of two glucose units and is produced from starch digestion. Lactose (Gal beta-1,4 Glc), the sugar in milk, contains galactose and glucose and is hydrolyzed by lactase; lactose intolerance results from lactase deficiency. Sucrose (Glc alpha-1,2-beta Fru), common table sugar, contains glucose and fructose. Because the linkage involves both anomeric carbons, sucrose is a non-reducing sugar with no free anomeric carbon. Cellobiose (Glc beta-1,4 Glc) is produced from cellulose digestion and features a beta linkage.
Reducing vs. Non-Reducing Sugars
A reducing sugar has a free anomeric carbon that can open to the aldehyde or ketone form and act as a reducing agent. Maltose, lactose, and cellobiose are all reducing sugars, detectable by Benedict's or Fehling's reagent (Cu2+ is reduced to Cu+, producing a red precipitate). A non-reducing sugar has no free anomeric carbon; sucrose is the classic example.
VI. Polysaccharides
Storage Polysaccharides
Starch, the storage polysaccharide of plants, consists of two components: amylose, which is unbranched with alpha-1,4-linked glucose forming a helical structure, and amylopectin, which is branched with alpha-1,4 linkages and alpha-1,6 branches every 24 to 30 residues. Glycogen, the storage polysaccharide of animals, is similar to amylopectin but more highly branched, with alpha-1,6 branches every 8 to 12 residues. Glycogen is stored primarily in the liver and skeletal muscle. Its high degree of branching provides many non-reducing ends for rapid glucose mobilization.
Structural Polysaccharides
Cellulose, the structural polysaccharide of plants, consists of linear chains of beta-1,4-linked glucose. These extended, flat chains form hydrogen bonds between adjacent chains, creating strong fibers. Humans lack cellulase and therefore cannot digest cellulose, which serves as dietary fiber. Chitin, found in arthropod exoskeletons and fungal cell walls, consists of beta-1,4-linked N-acetylglucosamine.
<image>A comparison figure of polysaccharide structures. Panel A: Amylose shown as a helical chain of alpha-1,4-linked glucose with a close-up of the glycosidic bond. Panel B: Glycogen/amylopectin shown with alpha-1,4 backbone and alpha-1,6 branch points, with the branching frequency difference noted. Panel C: Cellulose shown as extended flat chains with beta-1,4 linkages and inter-chain hydrogen bonds creating a fibrous structure. Panel D: A comparison of alpha-1,4 vs. beta-1,4 linkages showing how alpha linkages produce helical structures while beta linkages produce extended flat structures.</image>
VII. Glycoconjugates
Glycoproteins
Glycoproteins are proteins with covalently attached oligosaccharide chains. N-linked glycosylation attaches sugar to the amide nitrogen of asparagine within the sequon Asn-X-Ser/Thr (where X is not proline). This process begins in the ER and is further processed in the Golgi, with the core structure consisting of two GlcNAc plus three mannose residues. O-linked glycosylation attaches sugar to the hydroxyl of serine or threonine, occurs in the Golgi, and typically begins with GalNAc. Glycosylation serves multiple functions including protein folding, stability, cell recognition, and protection from proteolysis. The blood group antigens of the ABO system are determined by glycosyltransferases that add specific sugars to the H antigen.
Proteoglycans and Glycosaminoglycans (GAGs)
Proteoglycans are proteins with very large glycosaminoglycan chains attached. GAGs are long, unbranched polysaccharides consisting of repeating disaccharide units, typically one amino sugar plus one uronic acid. They are highly negatively charged due to sulfate and carboxylate groups, and they attract water and cations to form a gel-like matrix. Hyaluronic acid (hyaluronan) contains GlcNAc and glucuronic acid without sulfation and is found in joint fluid and vitreous humor. Chondroitin sulfate contains GalNAc-sulfate and glucuronic acid and is found in cartilage. Heparan sulfate and heparin contain GlcNAc/GlcN-sulfate and iduronic acid/glucuronic acid and function as anticoagulants. Keratan sulfate contains GlcNAc and galactose and is found in the cornea and cartilage.
