Carbohydrates: Definition and Roles

Carbohydrate Definition & Classification

• Polyhydroxyaldehydes or polyhydroxyketones with general formula (CH2O)n.
• May contain nitrogen, sulfur, or phosphorus.
• Exist in linear or cyclic forms.
• Include oligomers and polymers that can form these compounds upon hydrolysis.
• Also known as saccharides, with names ending in "-ose".
• Classified by their monosaccharide units:
  • Monosaccharides: Single unit of polyhydroxyaldehydes or ketones (e.g., glucose, fructose, erythrose, etc.)
  • Oligosaccharides: Few units linked by ether bonds (e.g., sucrose, a disaccharide containing glucose and fructose).
  • Polysaccharides (Glycans): More than 20 monosaccharide units (some have 100,000+ units). They can be linear (e.g., amylose) or branched (e.g., amylopectin, glycogen).

Carbohydrate Roles

• Energy generation and storage: The primary energy source in metabolism through oxidation.
• Structural role: Found in plants (cellulose), bacterial cell walls, and insect exoskeletons.
• Inactive ingredients (excipients): Used in tablets, capsules, and other pharmaceuticals.
• Osmolites: Contribute to osmotic pressure inside and outside of cells.
• Recognition elements: Involved in immunity, immune responses, and cell identity/recognition.

Monosaccharide Types & Nomenclature

• Two main types: polyhydroxyaldehydes (aldoses) and polyhydroxyketones (ketoses).
• Classified by the number of carbon atoms:
  • Trioses
  • Tetroses
  • Pentoses
  • Hexoses

Monosaccharide Chirality

• Smallest monosaccharide is glyceraldehyde, which has two stereoisomers.
• Most natural sugars have a D relative configuration.
• Dihydroxyacetone is a ketotriose with no stereoisomers.

Monosaccharide Series: Aldoses

• Most natural sugars have a D relative configuration.
• Each chiral carbon generates two enantiomers.
• A sugar with 'n' chiral carbons has 2n stereoisomers.
• Only half of these stereoisomers will have the D-relative configuration.

Monosaccharide Series: Ketoses

• Refer to provided image (Figure 8 in the original text).

Monosaccharide Series: Epimers

• Two sugars that differ only in the configuration of one chiral carbon atom.

Hexose

• Includes aldohexose and ketohexose examples.
• See figure 10 for structural representations of D-glucose, D-galactose, D-fructose, and L-galactose.

Monosaccharides: Cyclic Structure

• Monosaccharides exhibit special properties due to the presence of both alcohol and carbonyl functionalities in their molecules.
• Leads to high reactivity.

Monosaccharides: Cyclic Structure - Anomers

• Cyclization creates a new chiral center.
• Two stereoisomers, differing only in stereochemistry at the hemiacetalic carbon, are called anomers.
• Alpha and Beta anomers are shown in the figure 12.

Monosaccharides: Mutarotation

• Glucose and fructose have anomers, these are stereoisomers that differ in their configuration at the anomeric carbon.
• α-D-glucopyranose is 36.4% at equilibrium, while β-D-glucopyranose is 63.5%.
• The interconversion of the two anomers via the acyclic form is called mutarotation.
• The stability of the anomers is dependent on the position of the hydroxyl groups.
• α-D-glucopyranose has an axial hydroxyl group, while β-D-glucopyranose has an equatorial hydroxyl group.
• Equatorial hydroxyl groups are more stable due to less steric hindrance.
• α and β are different configurations, not conformations, and are diastereomers.

Reducing Properties of Monosaccharides

• Glucose is a reducing sugar because it can be oxidized to D-gluconate.
• Copper is reduced from +2 to +1 in the Fehling's reaction, which is a test for reducing sugars.
• Cyclic forms need a free glycosidic OH to display reducing properties.

Glucose Measurement in Diagnosis and Treatment of Diabetes

• Glucose oxidase method is used in testing strips, and the reaction produces a colored product.
• Hexokinase method uses the enzyme hexokinase to convert glucose to glucose-6-phosphate.
• The amount of NADPH produced is proportional to the amount of glucose.

Disaccharides

• Disaccharides contain a glycosidic bond which is formed by dehydration.
• Reducing disaccharides have one free anomeric OH, while non-reducing disaccharides have both anomeric OHs linked.
• Lactose is a reducing disaccharide found in milk, and it is broken down by lactase.
• Sucrose is a non-reducing disaccharide commonly known as table sugar.
• Sucrose is the main circulating sugar in plants.
• Trehalose is a non-reducing disaccharide found in insects.

Oligosaccharides: Cyclodextrins

• Cyclodextrins are cyclic oligomers of D-glucose linked α1→4.
• The most common cyclodextrins have 6, 7, or 8 glucose units (α, β, γ-cyclodextrins).
• They have a toroidal structure with a hydrophilic exterior and a hydrophobic interior.
• They can form host-guest complexes with lipophilic drugs.

Polysaccharides: Constitution and Topology

• Polysaccharides are polymers of monosaccharides.
• Homopolysaccharides are made up of the same type of monosaccharide, while heteropolysaccharides are made up of different types of monosaccharides.

Fuel-Storage Homopolysaccharides

• Starch is a mixture of amylose and amylopectin, which are polymers of D-glucose.
• Amylose is a linear polymer linked α1→4, while amylopectin is a branched polymer linked α1→4 and α1→6.
• Glycogen is a branched polymer of D-glucose similar to amylopectin but with more branching.
• Starch and glycogen are storage polysaccharides.

Cellulose

• Cellulose is a linear polymer of D-glucose linked β1→4.
• It is highly insoluble due to inter- and intra-chain hydrogen bonding.
• Cellulose can be used in pharmaceutical formulations as an adsorbent, glidant, suspending agent, and diluent.

Chitin

• Chitin is a polymer of N-acetylglucosamine linked β1→4.
• It is found in the exoskeletons of insects.
• Chitin is similar in structure to cellulose.

Glycoconjugates: Peptidoglycans

• Peptidoglycans are a major component of bacterial cell walls.
• They are made up of repeating disaccharide units of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).
• Peptidoglycans are cross-linked by short peptides.
• Peptidoglycans are essential for bacterial cell wall integrity and are targeted by antibiotics like penicillin.

Synthesis of Bacterial Peptidoglycan

• Penicillin inhibits the transpeptidase enzyme, which is responsible for cross-linking peptidoglycans.
• This weakens the bacterial cell wall and can lead to bacterial cell lysis.

Penicillins: General Structure and Representatives

• Penicillins have a β-lactam ring and a thiazolidine ring.
• Examples of penicillins include ampicillin and amoxicillin.

Penicillins: Mechanism of Action

• Penicillins bind to the active site of transpeptidase, preventing the formation of cross-links in peptidoglycans.

Penicillins: Mechanism of Inactivation

• Bacteria have evolved to produce β-lactamases, which cleave the β-lactam ring of penicillins, rendering them inactive.
• Clavulanic acid is a β-lactamase inhibitor that can be used to overcome bacterial resistance to penicillins.

Glucosaminoglycans

• Glucosaminoglycans are linear heteropolysaccharides composed of repeating disaccharide units.
• They are found in extracellular matrices and play important roles in cell signaling and tissue structure.

Heparin and Congeners

• Heparin is a highly sulfated glucosaminoglycan that is used as an anticoagulant.
• Heparin has the highest negative charge density of any known biological macromolecule.
• Low molecular weight heparin (LMWH) is a shorter version of heparin.

Oligosaccharide Links in Glycoproteins

• Oligosaccharides are found covalently linked to proteins in glycoproteins.
• They are involved in cell recognition and signaling.

Other Glycoconjugates

• Digoxin is a cardiac-active glycoside extracted from foxglove.
• It is used in the treatment of heart failure and atrial fibrillation.
• It contains a tri-digitoxose sugar molecule linked to an aglycone steroid.

Lipopolysaccharides

• Lipopolysaccharides are found on the surface of gram-negative bacteria.
• They are recognized by vertebrate immune systems.

Oligosaccharide Recognition: Lectins

• Lectins are proteins that bind carbohydrates with high affinity and specificity.
• They play important roles in cell-cell interactions and immune recognition.