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 play key roles in cell-cell recognition, especially in the immune system.

• Cellular Protection: They form protective structures like bacterial and plant cell walls.

• Cell Adhesion: Glycoproteins mediate cell adhesion processes.

• Biological Lubrication: Glycosaminoglycans act as lubricants in biological systems.

• Structural Roles: Carbohydrates such as cellulose and chitin build and maintain biological structures.

Carbohydrate Terminology

Carbohydrates are classified based on their structure and complexity.

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

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

• Polysaccharide: Polymers formed from multiple saccharide units; can be homopolysaccharides (one type of monomer) or heteropolysaccharides (multiple types).

• Glycan: Generic term for oligosaccharides and polysaccharides.

General Formula and Classes

Monosaccharides follow a general formula and are classified by their functional groups.

• General formula: $C_n(H_2O)_n$

• When $n=1$: formaldehyde; $n=2$: acetaldehyde; $n=3-9$: sugars.

• Aldoses: Monosaccharides with an aldehyde group.

• Ketoses: Monosaccharides with a ketone group.

Aldoses and Ketoses

Monosaccharides are further classified by the position of their carbonyl group.

• Glyceraldehyde: An aldose (triose, $n=3$ carbons).

• Dihydroxyacetone: A ketose (triose).

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

Chirality and Stereoisomerism

Monosaccharides are chiral molecules, leading to various stereoisomers.

• Chirality: Monosaccharides have asymmetric carbons (e.g., C2 in glyceraldehyde).

• Enantiomers: Optical isomers that are nonsuperimposable mirror images (designated as D and L forms).

• Fischer Projections: Compact way to represent stereochemistry.

• Wedge-dash representations: Show three-dimensional arrangement.

Diastereomers

Compounds with more than one asymmetric carbon can have diastereomers.

• Diastereomers: Optical isomers that are not mirror images.

• Convention: D and L refer to the configuration of the asymmetric carbon farthest from the carbonyl carbon.

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

• Ketotetrose erythrose has only two enantiomers and no diastereomers.

Stereochemical Relationships

The stereochemistry of aldoses and ketoses can be visualized in hierarchical diagrams.

• Aldoses: Multiple stereoisomers based on the number of asymmetric carbons.

• Ketoses: Fewer stereoisomers due to fewer asymmetric centers.

Ring Structures of Monosaccharides

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

• Furanose: Five-membered ring.

• Pyranose: Six-membered ring.

• Anomeric center: New asymmetric center formed during cyclization; anomers are designated as α or β.

• Haworth projection: Common way to depict ring structures.

Epimers and Conformational Isomers

Isomers can differ in configuration at a single carbon or in their three-dimensional conformation.

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

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

9.2 Derivatives of the Monosaccharides

Phosphate Esters

Sugar phosphates are key intermediates in metabolism and biosynthesis.

• Sugar phosphates: Formed by esterification of a hydroxyl group with phosphate.

• Example: β-D-Glucose-1-phosphate is involved in glycogen synthesis.

Lactones and Sugar Acids

Monosaccharides can be oxidized to form acids and lactones.

• Aldonic acids: Oxidation at C1 yields aldonic acids, which are in equilibrium with lactone forms.

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

Alditols

Reduction of the carbonyl group in monosaccharides produces alditols.

• Alditols: Polyhydroxy alcohols formed by reduction of the carbonyl group.

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

Amino Sugars

Amino sugars are important components of polysaccharides and glycoproteins.

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

• Examples: β-D-glucosamine, β-D-galactosamine.

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

Glycosides

Glycosides are formed by the reaction of the anomeric carbon with another compound.

• O-glycoside: Formed by elimination of water between the anomeric hydroxyl and another hydroxyl group.

• Glycosidic bond: The covalent bond formed in this process.

9.3 Oligosaccharides

Distinguishing Features of Disaccharides

Disaccharides are oligosaccharides composed of two monosaccharide units.

• Features:

  1. Sugar monomers and their stereochemistry

  2. Carbons involved in the linkage

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

  4. Configuration of the anomeric carbon (α or β)

• Example abbreviation: $\alpha$-D-Glcp(1→2)-β-D-Fruf (p=pyranose; f=furanose)

Writing the Structure of Disaccharides

Disaccharide structures are written using conventions for naming and linkage.

• Nonreducing end is placed on the left.

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

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

• Carbons involved in glycosidic bond formation are numbered and indicated by arrows (e.g., 1→4).

Representative Disaccharides and Their Biochemical Roles

Disaccharides have diverse natural occurrences and physiological 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 polymers
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 but require activation due to unfavorable thermodynamics.

• Condensation reaction: Elimination of water forms glycosidic bonds between saccharide monomers.

• Thermodynamics: The reaction has $\Delta G^\circ \approx +15$ kJ/mol, so activation is needed.

• Activation: In lactose biosynthesis, UDP-galactose acts as a high-energy derivative to facilitate bond formation.

9.4 Polysaccharides

Homopolysaccharides and Heteropolysaccharides

Polysaccharides are large carbohydrate polymers with diverse functions.

• Homopolysaccharides: Composed of one type of monomer.

• Heteropolysaccharides: Composed of more than one type of monomer.

• Functional types:

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

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

  3. Lubricants (e.g., glycosaminoglycans)

Energy Storage Polysaccharides: Starch and Glycogen

Starch and glycogen are the main energy storage polysaccharides in plants and animals, respectively.

• Starch: Found in plants; contains both amylopectin (α1→6 branches) and amylose (α1→4 unbranched polymer).

• Glycogen: Found in animals and microbes; similar to amylopectin but with higher molecular weight and more frequent branching.

Structural Polysaccharides: Cellulose and Chitin

Structural polysaccharides provide rigidity and protection in plants, fungi, and animals.

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

• Chitin: Homopolymer of N-acetyl-D-glucosamine; major component of exoskeletons in arthropods and mollusks.

Glycosaminoglycans

Glycosaminoglycans are repeating disaccharide polymers with structural and functional roles in vertebrates.

• Important in connective, epithelial, and neural tissues.

• Form matrices for proteins in skin and connective tissues.

• Act as lubricants and viscosity-increasing agents in body fluids.

• Function as anticoagulants (e.g., heparin).

Peptidoglycans

Peptidoglycans are complex polysaccharide-peptide structures found in bacterial cell walls.

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

• Target of antibiotics such as penicillin, which inhibit crosslinking during synthesis.

9.5 Glycoproteins

Linking Saccharide Chains to Proteins

Glycoproteins are proteins covalently linked to oligosaccharide or polysaccharide chains, with diverse biological functions.

• More than half of eukaryotic proteins are glycoproteins.

• N-linked glycoproteins: Saccharide chains attached to the amide group of asparagine residues.

• O-linked glycoproteins: Saccharide chains attached to the hydroxyl group of threonine or serine residues.

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

Blood-Group Antigens and Erythropoietin

Glycoproteins play key roles in blood-group antigenicity and hormone function.

• ABO blood types: Determined by O-linked glycoproteins on erythrocyte surfaces.

• Erythropoietin (EPO): A glycoprotein hormone synthesized in the kidney, stimulating red blood cell production; contains both O- and N-linked oligosaccharides.

• Recombinant EPO is used therapeutically and sometimes misused in sports.