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.

• Storage and generation of energy: Carbohydrates such as glucose, glycogen, and starch serve as primary energy sources and energy reserves.

• 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.

• Building and maintaining biological structure: Structural carbohydrates such as cellulose and chitin provide rigidity and support.

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; may be homopolysaccharides (one type of monomer) or heteropolysaccharides (multiple types of monomers).

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

• Two classes: Aldoses (aldehyde group) and Ketoses (ketone group).

Representative Carbohydrates

Examples include glucose, maltose, and polymers such as glycogen.

Aldoses and Ketoses

Monosaccharides are further classified based on the position of their carbonyl group.

• Glyceraldehyde: An aldose (aldehyde group at C1).

• Dihydroxyacetone: A ketose (ketone group at C2).

• Monosaccharides with three carbons are trioses ($n=3$), four are tetroses, five are pentoses, six are hexoses, and seven are heptoses.

Enantiomers

Monosaccharides are chiral molecules, often existing as optical isomers.

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

• Enantiomers: Nonsuperimposable mirror images, designated as D and L forms.

• Fischer projections: Compact way to represent stereochemistry.

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

Diastereomers

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

• Diastereomers: Optical isomers that are not mirror images.

• D and L notation: Refers 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

Aldoses and ketoses have complex stereochemical relationships, often depicted in hierarchical diagrams.

Ring Structures

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

• Five-membered (furanose) and six-membered (pyranose) rings: Common forms of cyclic sugars.

• Anomeric center: Cyclization creates a new asymmetric center, leading to α or β anomers.

• Haworth projection: Used to represent cyclic forms.

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

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

Terminology for Carbohydrate Stereochemistry

• Anomers: Stereoisomers differing at the anomeric carbon.

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

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

9.2 Derivatives of the Monosaccharides

Phosphate Esters

Sugar phosphates are important intermediates in metabolism, functioning as activated compounds in biosynthetic pathways.

• Example: β-D-Glucose-1-phosphate

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, such as β-D-glucuronic acid.

Alditols

Reduction of the sugar carbonyl group yields alditols.

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

Amino Sugars

Amino sugars are carbohydrates in which at least one hydroxyl group is replaced by an amine group.

• Found in many polysaccharides and glycoproteins.

• 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 elimination of water between the hydroxyl group of the anomeric carbon of a cyclic saccharide and the hydroxyl group of another compound.

• This bond is called a glycosidic bond.

• Example: Formation of methyl-α-D-glucopyranoside.

9.3 Oligosaccharides

Distinguishing Features of Disaccharides

Disaccharides are oligosaccharides composed of two monosaccharide units.

• Four major features:

  1. The sugar monomers involved and their stereochemistry

  2. The carbons involved in the linkage

  3. The order of sugars (chemical reactivity of functional groups)

  4. The configuration of the anomeric carbon (α or β)

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

Writing the Structure of Disaccharides

• Start with the nonreducing end on the left.

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

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

• Number the carbons involved in glycosidic bond formation as in open structures, and indicate connections by arrows (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 α(1→2) Fru β	Many fruits, seeds, honey	Final product of photosynthesis; primary energy source in many plants
Lactose	Gal β(1→4) Glc	Milk, some plant sources	Major animal energy source
α,α-Trehalose	Glc α(1→1) Glc	Yeast, other fungi, insect blood	Major circulatory sugar in insects; used for energy
Maltose	Glc α(1→4) Glc	Plants (starch) and animals (glycogen)	Derived from starch and glycogen digestion
Cellobiose	Glc β(1→4) Glc	Plants (cellulose)	Cellulose polymer dimer
Gentiobiose	Glc β(1→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, which are thermodynamically unfavored and require activation.

• $\Delta G^\circ$ for glycosidic bond formation is about +15 kJ/mol.

• Activation is achieved by using high-energy derivatives, such as UDP-galactose in lactose biosynthesis.

9.4 Polysaccharides

Homopolysaccharides and Heteropolysaccharides

Polysaccharides are large carbohydrate polymers classified by their monomer composition.

• Homopolysaccharides: Made of one type of monomer (e.g., cellulose, starch).

• Heteropolysaccharides: Made 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., glycosaminoglycans)

Energy Storage Polysaccharides

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

• Starch: Contains both amylopectin (α(1→6) branches) and amylose (α(1→4) unbranched polymer).

• Glycogen: Similar to amylopectin but with higher molecular weight and more frequent branch points.

Structural Polysaccharides

Structural polysaccharides provide rigidity and support in various organisms.

• 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 polymers of repeating disaccharide units with structural and nonstructural roles in vertebrates.

• Important in connective, epithelial, and neural tissues.

• Form matrices for proteins in skin and connective tissues.

• Act as lubricants and anticoagulants (e.g., heparin).

Peptidoglycans

Peptidoglycans are cross-linked polysaccharide-peptide complexes found in bacterial cell walls.

• Composed of alternating copolymers of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).

• Crosslinked through short peptides.

• Target of antibiotics such as penicillin.

9.5 Glycoproteins

Linking Saccharide Chains to Proteins

Glycoproteins are proteins with covalently attached oligosaccharide or polysaccharide chains.

• Chains can be N-linked (to asparagine) or O-linked (to threonine or serine).

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

Blood-Group Antigens

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

Erythropoetin (EPO)

EPO is a glycoprotein hormone synthesized in the kidney that stimulates red blood cell production.

• Contains both O- and N-linked oligosaccharides.

• Used therapeutically to counteract anemia during cancer chemotherapy.

• Recombinant EPO is sometimes misused by athletes to enhance performance.

Additional info: Stereochemical diagrams and molecular models referenced in the notes are standard visual aids in biochemistry textbooks for illustrating isomerism and ring structures.