Carbohydrates: Structure, Classification, and Biological Roles

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).

• Glycan: Generic term for oligosaccharides and polysaccharides.

General Formula

• Carbohydrates have the empirical formula $C_n(H_2O)_n$.

• For $n=1$: formaldehyde; $n=2$: acetaldehyde; $n=3-9$: sugars with typical carbohydrate properties.

Classification by Functional Group

• Aldoses: Monosaccharides with an aldehyde group.

• Ketoses: Monosaccharides with a ketone group.

Representative Carbohydrates

• Examples include glucose (monosaccharide), maltose (disaccharide), and amylose (polysaccharide).

Aldoses and Ketoses

• Glyceraldehyde (an aldose) and dihydroxyacetone (a ketose) are the simplest monosaccharides (trioses, $n=3$ carbons).

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

Enantiomers

Monosaccharides are often chiral, meaning they have asymmetric carbon atoms.

• Chirality: For example, the second carbon of glyceraldehyde has four different substituents.

• Enantiomers: Optical isomers that are nonsuperimposable mirror images (e.g., D- and L-glyceraldehyde).

Fischer and Wedge-Dash Projections

• Fischer projections are used to represent stereochemistry compactly.

• Wedge-dash representations show three-dimensional arrangements.

Diastereomers

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

• Diastereomers: Optical isomers 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

• Aldoses and ketoses can be organized in family trees based on their stereochemistry.

Ring Structures of Monosaccharides

Monosaccharides can cyclize to form ring structures, creating new stereocenters.

• Furanose: Five-membered ring.

• Pyranose: Six-membered ring.

• Cyclization creates an anomeric center, leading to 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 (conformational isomers).

Terminology for Carbohydrate Stereochemistry

• Anomers: Stereoisomers differing at the anomeric carbon (e.g., α- and β-glucopyranose).

• Epimers: Stereoisomers differing at one carbon other than the anomeric carbon (e.g., glucose and mannose).

• Conformational isomers: Same configuration, different three-dimensional conformation (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 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 (e.g., β-D-glucosamine, β-D-galactosamine).

• Derivatives include N-acetylglucosamine, muramic acid, and N-acetylmuramic acid.

Glycosides

• Formed by elimination of water between the anomeric hydroxyl of a cyclic saccharide and the hydroxyl 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.

• 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 α-D-Glcp(1→2)β-D-Fruf (p = pyranose, f = furanose).

Writing the Structure of Disaccharides

• Start with the nonreducing end on the left and use abbreviated monosaccharide names.

• 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 (e.g., 1→4).

Examples of Disaccharides

• Disaccharides with α-connections: maltose, trehalose.

• Disaccharides with β-connections: lactose, cellobiose.

Representative Disaccharides and Their Biochemical Roles

Disaccharide	Structure	Natural Occurrence	Physiological Role
Sucrose	Glc(α1→2)Fru(β)	Many fruits, seeds, honey	Photosynthesis product; 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, fungi, insect blood	Circulatory sugar in insects; energy storage
Maltose	Glc(α1→4)Glc	Plants (starch), animals (glycogen)	Starch/glycogen digestion product
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 condensation reactions (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., glycosaminoglycans)

Energy Storage Polysaccharides

• 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.

• Cellulose forms the main component of plant cell walls.

• Chitin provides a matrix for mineralization, similar to collagen in animals.

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.

9.5 Glycoproteins

Linking Saccharide Chains to Proteins

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

• N-linked: Attached to the amide group of asparagine side chains.

• O-linked: Attached to the hydroxyl group of serine or threonine side chains.

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

Blood-Group Antigens

• ABO blood types are determined by O-linked glycoproteins on the surface of red blood cells.

Erythropoietin (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; recombinant EPO is sometimes misused for performance enhancement.