5

9.1 Monosaccharides

Diverse Functions of Carbohydrates

Carbohydrates are essential biomolecules with a wide range of biological functions in living organisms.

• Energy Storage and Generation: Carbohydrates such as glucose, glycogen, and starch serve as primary energy sources and storage forms.

• Molecular Recognition: Carbohydrates are involved in cell-cell recognition, notably in the immune system.

• Cellular Protection: Structural carbohydrates form protective barriers, e.g., bacterial and plant cell walls.

• Cell Adhesion: Glycoproteins mediate cell adhesion processes.

• Biological Lubrication: Glycosaminoglycans act as lubricants in joints and other tissues.

• Structural Roles: Polysaccharides like cellulose and chitin provide structural integrity to plants and arthropods.

Carbohydrate Terminology

• Monosaccharide: Simple sugars and their derivatives containing 3 to 9 carbon atoms.

• Oligosaccharide: Molecules formed by linking several monosaccharides (e.g., disaccharides).

• Polysaccharide: Polymers composed of many monosaccharide units; can be homopolysaccharides (one type of monomer) or heteropolysaccharides (multiple types of monomers).

• Glycan: Generic term for oligosaccharides and polysaccharides.

General Formula: $C_n(H_2O)_n$

• When $n=1$: formaldehyde

• When $n=2$: acetaldehyde

• When $n=3-9$: compounds with properties of sugars

Monosaccharides are classified as aldoses (aldehyde group) or ketoses (ketone group).

Aldoses and Ketoses

• Glyceraldehyde is the simplest aldose (triose).

• Dihydroxyacetone is the simplest ketose (triose).

• Monosaccharides with four carbons are tetroses, five carbons are pentoses, six are hexoses, and seven are heptoses.

Enantiomers

Monosaccharides are chiral molecules, meaning they have at least one carbon atom with four different substituents, leading to optical isomerism.

• Enantiomers: Non-superimposable mirror images (e.g., D- and L-glyceraldehyde).

• Fischer Projections: A two-dimensional representation of stereochemistry.

• Wedge-Dash Notation: Three-dimensional representation of stereochemistry.

Diastereomers

• Compounds with more than one asymmetric carbon can be enantiomers or diastereomers.

• Diastereomers: Stereoisomers that are not mirror images.

• D- and L- refer to the configuration of the asymmetric carbon farthest from the carbonyl group.

• Example: D-Threose and L-Erythrose are diastereomers.

• Ketotetrose erythulose has only two enantiomers and no diastereomers.

Stereochemical Relationships of Aldoses and Ketoses

Stereochemical relationships can be visualized in tree diagrams, showing how different sugars are related by changes at specific chiral centers.

Ring Structures of Monosaccharides

• Sugars can cyclize to form five-membered (furanose) or six-membered (pyranose) rings.

• Cyclization creates a new asymmetric center at the anomeric carbon, resulting in α or β anomers.

• Ring structures are often depicted using Haworth projections.

• Glucose and mannose are epimers (differ at C2); glucose and galactose are epimers at C4.

• Pyranose rings can adopt chair or boat conformations, which are examples of conformational isomers.

Terminology for Carbohydrate Stereochemistry

• Anomers: Stereoisomers differing at the anomeric carbon (α or β).

• Epimers: Stereoisomers differing at one carbon other than the anomeric carbon.

• Conformational Isomers: Molecules with the same stereochemical configuration but different three-dimensional conformations (e.g., chair vs. boat forms).

9.2 Derivatives of the Monosaccharides

Phosphate Esters

Sugar phosphates are important intermediates in metabolism, acting as activated compounds in biosynthetic and catabolic pathways.

• Example: β-D-Glucose-1-phosphate is a key intermediate in glycogen synthesis and breakdown.

Lactones and Sugar Acids

• Monosaccharides can be oxidized at C1 to yield aldonic acids, which are in equilibrium with their lactone forms.

• Oxidation at C6 yields uronic acids (e.g., β-D-glucuronic acid).

Alditols

• Reduction of the sugar carbonyl group yields an alditol (sugar alcohol).

• Example: Reduction of glucose forms D-glucitol (sorbitol).

Amino Sugars

• At least one hydroxyl group is replaced by an amine group.

• Common in polysaccharides and glycoproteins.

• Examples: β-D-glucosamine, β-D-galactosamine, β-D-N-acetylglucosamine, muramic acid, N-acetylmuramic acid.

Glycosides

• Formed by the elimination of water between the anomeric hydroxyl group of a cyclic saccharide and the hydroxyl group of another compound, yielding an O-glycoside.

• The bond formed is called a glycosidic bond.

9.3 Oligosaccharides

Distinguishing Features of Disaccharides

Disaccharides are oligosaccharides composed of two monosaccharide units joined by a glycosidic bond. Their properties depend on:

• The sugar monomers involved and their stereochemistry

• The carbons involved in the linkage

• The order of sugars (determined by the chemical reactivity of functional groups involved in linkage)

• The configuration of the anomeric carbon (α or β)

Example: Sucrose is abbreviated as $\alpha$-D-Glcp(1→2)-β-D-Fruf (p = pyranose, f = furanose)

Writing the Structure of Disaccharides

• Start with the nonreducing end on the left, using the abbreviated monosaccharide name.

• Designate anomeric and enantiomeric forms by prefixes (e.g., β-, D-).

• Indicate ring configuration by a suffix (p for pyranose, f for furanose).

• Number the carbons involved in glycosidic bond formation as in open-chain forms, and indicate the linkage (e.g., 1→4).

Representative Disaccharides and Their Biochemical Roles

Disaccharide	Structure	Natural Occurrence	Physiological Role
Sucrose	Glc(α1→2)Fru(β)	Many fruits, seeds, honey	Final product of photosynthesis; primary energy source in many plants
Lactose	Gal(β1→4)Glc	Milk, some plant sources	Major animal energy source
α,α-Trehalose	Glc(α1→1)Glc	Yeast, other fungi, insect blood	Major circulatory sugar in insects; used for energy storage
Maltose	Glc(α1→4)Glc	Plants (starch) and animals (glycogen)	Derived from starch and glycogen digestion
Cellobiose	Glc(β1→4)Glc	Plants (cellulose)	Cellulose polymer dimer
Gentiobiose	Glc(β1→6)Glc	Some plants (e.g., gentians)	Constituent of plant glycosides and some polysaccharides

Stability and Formation of Glycosidic Bonds

• Glycosidic bonds are formed by a condensation reaction (elimination of water).

• The reaction is thermodynamically unfavored ($\Delta G^\circ \approx +15$ kJ/mol), requiring activation.

• In lactose biosynthesis, UDP-galactose (a high-energy derivative) condenses with glucose to form lactose.

9.4 Polysaccharides

Homopolysaccharides and Heteropolysaccharides

• Homopolysaccharides: Composed of one type of monosaccharide (e.g., cellulose, starch, glycogen).

• Heteropolysaccharides: Composed of more than one type of monosaccharide (e.g., glycosaminoglycans).

• Functional categories:

  • Energy storage (e.g., starch, glycogen)

  • Structural (e.g., cellulose)

  • Lubricants (e.g., some glycosaminoglycans)

Energy Storage Polysaccharides: Starch and Glycogen

• Starch (plants): Contains both amylopectin (α1→6 branched glucose polymer) and amylose (α1→4 unbranched polymer).

• Glycogen (animals/microbes): Similar to amylopectin but with higher molecular weight and more frequent, shorter branches.

• The secondary structure of amylose forms a helix stabilized by hydrogen bonds.

Structural Polysaccharides

• Cellulose: Major structural polysaccharide in plants; linear homopolymer of β-D-glucose linked by β(1→4) bonds.

• Chitin: Homopolymer of N-acetyl-D-glucosamine; structural component in fungi, algae, mollusks, and arthropods.

Glycosaminoglycans

• Polymers of repeating disaccharide units.

• Serve structural and nonstructural roles in vertebrates (e.g., connective, epithelial, and neural tissues).

• Form matrices for proteins in skin and connective tissues; act as lubricants and anticoagulants (e.g., heparin).

Peptidoglycans

• Major component of bacterial cell walls (especially Gram-positive bacteria).

• Composed of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) crosslinked by short peptides.

• Target of antibiotics such as penicillin, which inhibit crosslinking and thus cell wall synthesis.

9.5 Glycoproteins

Linking Saccharide Chains to Proteins

• More than half of all eukaryotic proteins are glycoproteins (proteins with covalently attached oligosaccharide or polysaccharide chains).

• Glycan chains can be N-linked (to asparagine side chain amide) or O-linked (to serine or threonine hydroxyl groups).

• Functions include protein distribution, cell adhesion, and cell recognition.

Blood-Group Antigens and Glycoproteins

• ABO blood group antigens are O-linked glycoproteins on the surface of red blood cells.

Erythropoietin A (EPO)

• Hormone produced in the kidney that stimulates red blood cell production.

• EPO is a glycoprotein with both O- and N-linked oligosaccharides.

• Used therapeutically to treat anemia, especially during cancer chemotherapy; sometimes misused for athletic performance enhancement.