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: Large polymers of saccharide units; can be homopolysaccharides (one type of monomer) or heteropolysaccharides (multiple types of monomers).

• 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; $n=3-9$: compounds with sugar properties.

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: tetroses; five: pentoses; six: hexoses; seven: heptoses.

Chirality and Stereoisomerism

• Chirality: Monosaccharides are chiral; e.g., the second carbon of glyceraldehyde has four different substituents.

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

• Fischer Projections: Compact way to represent stereochemistry; wedge-dash diagrams also used.

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 the number of carbons and stereochemistry.

Ring Structures of Monosaccharides

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

• Cyclization creates a new asymmetric center (the anomeric center), leading to α or β anomers.

• Ring structures are depicted using Haworth projections.

• Common hexoses: β-D-glucopyranose, β-D-mannopyranose, β-D-galactopyranose, β-D-fructofuranose.

• Epimers: Isomers differing in configuration at only one carbon (e.g., glucose and mannose at C2).

• Conformational isomers: Same stereochemical configuration, different three-dimensional conformation (e.g., chair and boat forms of pyranose rings).

Terminology for Carbohydrate Stereochemistry

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

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

• Conformational isomers: Molecules with the same configuration but different 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.

• 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 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

• Four major features:

  1. Sugar monomers involved and their stereochemistry

  2. Carbons involved in the linkage

  3. Order of sugars (determined by chemical reactivity of functional groups)

  4. 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

• Nonreducing end is placed on the left with abbreviated monosaccharide name.

• Anomeric and enantiomeric forms are indicated by prefixes (e.g., β-, D-).

• Ring configuration is indicated by a suffix (p for pyranose, f for furanose).

• Carbons involved in glycosidic bond formation are numbered as in open-chain forms; connections are indicated by arrows (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
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 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 monomer (e.g., cellulose, starch, glycogen).

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

• Functional categories:

  1. Energy storage polysaccharides (e.g., starch, glycogen)

  2. Structural polysaccharides (e.g., cellulose)

  3. Lubricants (e.g., some 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 β1→4 bonds.

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

• 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 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 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

• ABO blood types are determined by O-linked glycoproteins on erythrocyte surfaces.

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 (e.g., during cancer chemotherapy); sometimes misused for athletic performance enhancement.