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

• Glycan: Generic term for oligosaccharides and polysaccharides.

General Formula and Classification

• General Formula: $(CH_2O)_n$

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

• Monosaccharide Classes:

  • Aldoses: Monosaccharides with an aldehyde group.

  • Ketoses: Monosaccharides with a ketone group.

Representative Carbohydrates

• Examples include glucose (an aldose), maltose (a disaccharide), and amylose (a polysaccharide).

Aldoses and Ketoses

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

• Dihydroxyacetone: The simplest ketose (triose).

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

Enantiomers

Monosaccharides are chiral molecules, meaning they have asymmetric carbons and can exist as optical isomers.

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

• Enantiomers: Non-superimposable 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 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 classified based on the number and arrangement of their chiral centers.

• Epimers are isomers that differ in configuration at only one specific carbon atom.

Ring Structures of Monosaccharides

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

• Cyclization creates a new asymmetric center (the anomeric carbon), 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: Glucose and mannose differ at C2; glucose and galactose differ at C4.

• Pyranose rings can adopt chair and boat conformations (conformational isomers).

Terminology for Carbohydrate Stereochemistry

• Anomers: Stereoisomers differing at the anomeric carbon.

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

• Conformational Isomers: Same stereochemical 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.

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, such as 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

• 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, β-D-N-acetylglucosamine, muramic acid, N-acetylmuramic acid.

Glycosides

• 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, yielding an O-glycoside.

• The bond formed is called a glycosidic bond.

9.3 Oligosaccharides

Distinguishing Features of Disaccharides

• Four major features:

  1. The sugar monomers involved and their stereochemistry.

  2. The carbons involved in the linkage.

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

  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 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 as in open-chain forms; indicate connections by an arrow (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 a condensation reaction (elimination of water).

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

• In lactose biosynthesis, the activated sugar is UDP-galactose, which 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 branches) and amylose (α1→4 unbranched polymer).

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

Starch (Amylose and Amylopectin) and Glycogen

• Amylose forms a helical structure stabilized by hydrogen bonds.

• Amylopectin and glycogen are branched, allowing rapid mobilization of glucose units.

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 tissue, skin, neural tissue).

• Act as viscosity-increasing agents or lubricants (e.g., synovial fluid), and as anticoagulants (e.g., heparin).

Peptidoglycans

• Major component of bacterial cell walls, especially in 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, carrying 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, especially during cancer chemotherapy; recombinant EPO is sometimes misused for athletic performance enhancement.

Additional info: This summary integrates and expands upon the provided slides, ensuring all key concepts are explained with academic clarity and context for biochemistry students.