Carbohydrates Overview

Carbohydrates

• Polyhydroxyaldehydes or polyhydroxyketones with the general formula (CH2O)n, sometimes containing N, S, or P.
• Can be linear or cyclic.
• Also include oligomers and polymers, which form upon hydrolysis.
• Also called saccharides, named with the suffix “-ose”.
• Classified in monosaccharides, oligosaccharides, and polysaccharides.

Monosaccharides

• Single units of polyhydroxyaldehydes or ketones.
• Examples include glucose, fructose, erythrose.

Oligosaccharides

• Contain a few monosaccharide units linked via ether bonds.
• Sucrose is a disaccharide made up of one unit of D-glucose and one unit of D-fructose.

Polysaccharides

• Contain more than 20 monosaccharide units.
• Some have more than 100,000 units.
• Can be linear (e.g., amylose) or branched (e.g., amylopectin, glycogen).

Carbohydrate Roles

• Energy generation and storage: Oxidation of carbohydrates is the primary energy generating process in metabolism.
• Structural role in plants (cellulose), cell walls of bacteria, and exoskeleton of insects.
• Inactive ingredients in tablets, capsules, and other pharmaceutical formulations.
• Osmolites, contributing to osmotic pressure inside and outside the cells.
• Recognition elements in immunity, immune response, cell identity, and recognition.

Monosaccharides: Types and Nomenclature

• Two main types: polyhydroxyaldehydes (aldoses) and polyhydroxyketones (ketoses), determined by the position of the carbonyl group.
• Classified by the number of carbon atoms in the molecule, including trioses, tetroses, pentoses, and hexoses.

Monosaccharides: Chirality

• Smallest monosaccharide is glyceraldehyde, which has two stereoisomers.
• Most natural sugars have the D relative configuration, determined by the position of the hydroxyl group on the most distant chiral carbon from the carbonyl group.

Monosaccharides: Fischer Projection

• A two-dimensional representation of the three-dimensional molecular structure showing all chiral centers within a molecule.
• The longest carbon chain is written vertically with the most oxidized carbon at the top.
• Horizontal lines represent bonds projecting forward, vertical lines represent bonds projecting to the rear.
• Carbon atoms at the intersection of horizontal and vertical lines are not shown.
• Carbon atoms are numbered sequentially from the top.
• The D or L configuration is determined by the position of the hydroxyl group on the chiral carbon farthest from the carbonyl group: on the right for D configuration, and on the left for L configuration.

Carbohydrates: Classification and Structure

• Carbohydrates are organic compounds composed of carbon, hydrogen, and oxygen.
• They play crucial roles in living organisms, including energy storage, structural support, and cell recognition.
• Carbohydrates are classified based on their complexity: monosaccharides, disaccharides, oligosaccharides, and polysaccharides.
• Monosaccharides are the simplest sugars:
  • They can be classified as aldoses (contain an aldehyde group) or ketoses (contain a ketone group).
  • Each chiral carbon in a monosaccharide generates two enantiomers.
  • The number of stereoisomers for a sugar with "n" chiral carbons is 2^n.
  • Only half of these stereoisomers will have the D-relative configuration (found in most natural sugars).
  • Epimers are two sugars that differ only in the configuration of one chiral carbon atom.
• Monosaccharides can exist in cyclic forms:
  • The formation of a cyclic structure creates a new chiral center called the anomeric carbon.
  • The two stereoisomers that differ in stereochemistry at the anomeric carbon are called anomers.
  • The interconversion of the two anomers via the acyclic form is called mutarotation.
• Pyranose rings are not flat but adopt 3D conformations:
  • They exist in equilibrium between two chair forms: equatorial-equatorial (less steric hindrance, more stable) and axial-axial (more steric hindrance, less stable).
  • The most stable conformation of a pyranose ring is the one with the most substituents in equatorial positions.
  • Anomers are different configurations (not conformations), they are diastereomers and can only be interconverted by bond cleavage.
• Monosaccharides exhibit reducing properties:
  • They can reduce copper from +2 to +1 oxidation state, as demonstrated in Fehling's reaction.
  • This property is exhibited only if the sugar can adopt an acyclic form, or if the glycosidic OH is free in the cyclic form.
  • The ability to reduce oxidizing agents is a key factor in diagnosing diabetes.

Disaccharides

• Disaccharides consist of two monosaccharides linked by a glycosidic bond.
• Common disaccharides include:
  • Lactose (glucose and galactose): Reducing sugar, found in milk.
  • Sucrose (glucose and fructose): Non-reducing sugar, table sugar.
  • Trehalose (glucose and glucose): Non-reducing sugar, found in insects.

Polysaccharides

• Polysaccharides are polymers of monosaccharides linked together by glycosidic bonds.
• They are classified as homopolysaccharides (contain only one type of monosaccharide) or heteropolysaccharides (contain multiple types of monosaccharides).
• Homopolysaccharides play important roles in energy storage and structural support.
• Examples of homopolysaccharides include:
  • Starch:
    • A mixture of amylose (linear polymer of glucose units linked α1→4) and amylopectin (branched polymer of glucose units linked α1→4 and α1→6).
    • Amylose forms a helical structure due to intra-chain hydrogen bonding, allowing it to form inclusion complexes with iodine.
    • Amylopectin is highly branched, leading to a compact structure.
    • Starch is used as an excipient in pharmaceutical formulations.
  • Glycogen:
    • Highly branched polymer of glucose linked α1→4 and α1→6.
    • Serves as a storage polysaccharide in animal cells.
  • Cellulose:
    • Linear polymer of glucose linked β1→4.
    • Forms very tough fibers due to strong intra- and inter-chain hydrogen bonding.
    • It is a major structural component of plant cell walls.
    • Cellulose can be modified to create various derivatives with altered properties, used in pharmaceutical formulations.
  • Chitin:
    • Polymer of N-acetylglucosamine (NAG), linked β1→4.
    • Strong and resilient, similar in structure to cellulose.
    • Found in exoskeletons of arthropods and cell walls of fungi.
    • Chitin and chitosan are used in pharmaceutical formulations as excipients.

Glycoconjugates

• Peptidoglycans:
  • Are heteropolysaccharides composed of NAG and NAM (N-acetylmuramic acid) joined by β1→4 glycosidic bonds.
  • They form the rigid, protective outer layer (cell wall) of bacteria.
  • Peptidoglycans are cross-linked by short peptides, differing between Gram-positive and Gram-negative bacteria.
  • The synthesis of peptidoglycan is a complex, multi-step process involving multiple enzymes.
  • β-lactam antibiotics, such as penicillins, inhibit the cross-linking of peptidoglycans, weakening bacterial cell walls and leading to cell lysis.

Lectins

• Lectins are proteins that bind to carbohydrates.
• They play critical roles in cell recognition and adhesion.
• Examples of lectins include:
  • Selectins: Mediates cell recognition and adhesion, especially involved in the movement of white blood cells (leukocytes) to sites of inflammation.
  • Integrins: Act as receptors, mediating cell-cell and cell-extracellular matrix interactions.
• Examples of lectin-mediated functions:
  • Leukocyte rolling and migration: Selectins on endothelial cells bind glycoproteins on leukocytes, allowing them to roll along blood vessel walls and migrate to sites of inflammation.
  • Bacterial adherence: Some bacteria, such as Helicobacter pylori (which causes stomach ulcers) adhere to the gastric epithelium using lectins that bind to specific blood group antigens.

Goals and Objectives:

• Describe the importance of carbohydrates in living organisms.
• Distinguish between the different classes of carbohydrates.
• Identify the key structural features of each class of carbohydrate.
• Understand the different types of isomers that can exist in monosaccharides, including enantiomers, epimers, anomers, and different conformations.
• Explain the properties that make a sugar a reducing sugar.
• Describe the structure and function of polysaccharides, including starch, glycogen, cellulose, and chitin.
• Describe the structure and function of peptidoglycans.
• Explain the mechanism of action of β-lactam antibiotics, such as penicillins.
• Describe the function of lectins, including selectins and integrins.
• Provide examples of lectin-mediated functions in the body.