HK

Carbohydrates: Structure and Function

Carbohydrates

What are Carbohydrates?

  • Carbohydrates are the most widely distributed and abundant organic compounds on earth.
  • They are the building blocks of sugar units, also known as "hydrates of carbon."
  • The general formula for carbohydrates is Cn(H2O)n = (CH2O)_n.

Functions of Carbohydrates in Our Body:

  • (1) Energy Provision:
    • Carbohydrates provide the body with energy.
    • Glycogen is stored in muscle or liver.
    • Starch is stored in plant cells.
    • Most carbohydrates in foods are broken down into glucose.
    • Glucose in the blood is taken up by body cells and used to produce Adenosine Triphosphate (ATP), a fuel molecule.
    • Excess glucose can be stored for later use if the body has enough to fulfill current needs.
  • (2) Support/Structural Component:
    • Cellulose in cell walls provides structural support.
    • Glycosaminoglycans are found in cartilage.
    • Pectin is a structural compound in cell walls of plant materials.
  • (4) Cell Attachment and Cell-Cell Communication:
    • Carbohydrates play a role in cell attachment and communication within the extracellular matrix.
    • Components include collagen fiber, plasma membrane, integrin, proteoglycan complex, and fibronectin.
  • (5) Interaction with Other Macro-molecules:
    • Glycosylation is a common Post-Translational modification (occurs in the endomembrane system).
    • The sugar-phosphate backbone is present in DNA/RNA structure.

Carbohydrate Malfunctions

  • Disorders of carbohydrate metabolism include:
    • Diabetes: Elevated blood glucose levels.
    • Galactosemia: Inability to metabolize galactose.
    • Glycogen storage disease: Abnormal storage or processing of glycogen.
    • Lactose intolerance: Inability to properly digest lactose.

Classification of Carbohydrates:

Number of Carbons:

  • Three carbons: triose.
  • Four carbons: tetrose.
  • Five carbons: pentose.
  • Six carbons: hexose.
  • Seven carbons: heptose.
  • Etc.

Number of Carbohydrate Units:

  • Monosaccharides: One carbohydrate unit (simplest carbohydrates).
  • Disaccharides: Two carbohydrate units (complex carbohydrates).
  • Trisaccharides: Three carbohydrate units.
  • Polysaccharides: Many carbohydrate units.

Examples of Carbohydrate Classifications:

  • Monosaccharides: Glucose, Fructose, Galactose.
  • Disaccharides: Sucrose, Lactose, Maltose.
  • Oligosaccharides: Raffinose, Stachyose.
  • Polysaccharides: Starch, Glycogen, Cellulose.

Classification of Carbohydrates: Isomers

  • Isomers have the same molecular formula but different structures.

Constitutional Isomers (Structural Isomers):

  • Differ in the order of attachment of atoms.
  • Example: Glyceraldehyde and Dihydroxyacetone (both have the formula (C3H6O_3)).
  • Aldose: Carbonyl group (C=O) at C1, forming an aldehyde.
  • Ketose: Carbonyl group (C=O) at any carbon other than C1, forming a ketone.

Stereoisomers:

  • Atoms are connected in the same order but differ in spatial arrangement.
Enantiomers:
  • Nonsuperimposable mirror images; chiral molecules with optical activity.
  • Example: D-Glyceraldehyde and L-Glyceraldehyde (both have the formula (C3H6O_3)).
  • Fischer Projections and the D, L Notation:
    • Representation of a three-dimensional molecule as a flat structure.
    • Tetrahedral carbon represented by two crossed lines: the vertical line goes back behind the plane, and the horizontal line comes out of the plane.
    • Carbohydrates are designated as D- or L- based on the stereochemistry of the highest-numbered chiral carbon in the Fischer projection.
    • If the hydroxyl group on the highest-numbered chiral carbon points to the right, it is designated as D. If it points to the left, it is L.
    • Most naturally occurring carbohydrates are of the D- configuration.
Diastereoisomers:
  • Isomers that are not mirror images.
  • Aldopentoses (C5) have three chiral carbons and eight stereoisomers.
  • Aldohexoses (C6) have four chiral carbons and sixteen stereoisomers (number of stereoisomers = 2^n, where n = number of chiral carbons).
Epimers:
  • A type of diastereomer that differs in the configuration at only one asymmetric carbon atom within a molecule.
  • Example: Glucose and galactose (different at C4), glucose and mannose (different at C2).
Anomers:
  • A specific type of epimer that refers to stereoisomers differing in configuration at the anomeric carbon, which becomes chiral during ring closure in cyclic structures.

Cyclization:

  • Many common sugars exist in cyclic forms because they are thermodynamically more stable (lower energy).
  • Reaction of an alcohol with an aldehyde forms a hemiacetal.
  • Reaction of an alcohol with a ketone forms a hemiketal.
  • Pyranose Formation:
    • Formation of a six-membered ring.
    • Example: D-Glucose forms α-D-glucopyranose and β-D-glucopyranose.
    • α-anomer: OH on C1 points down.
    • β-anomer: OH on C1 points up.
  • Furanose Formation:
    • Formation of a five-membered ring.
    • Example: Fructose forms fructofuranose and fructopyranose.
  • The hemiacetal or hemiketal carbon of the cyclic form of carbohydrates is the anomeric carbon.
  • Carbohydrate isomers that differ only in the stereochemistry of the anomeric carbon are called anomers.
  • Converting Fischer Projections to Haworth formulas leads to cyclization and anomers.

Common Sugars in Ring Forms:

  • Examples include α-D-Glucose, D-Ribose, 2-Deoxy-D-ribose, α-D-Fructose, α-D-Galactose, and α-D-Mannose.

Chair and Boat Forms:

  • Cyclic structures can adopt chair or boat conformations.
  • The chair form has less steric hindrance and, therefore, lower energy, making it more stable.

Equilibrium between Cyclic Forms:

  • The pyranose form of glucose dominates (>99%) at equilibrium in aqueous solution.
  • Furanose forms and open-chain forms exist in smaller amounts.

Reducing Sugars:

  • Reducing sugars are mono- or disaccharides that donate electrons.
  • They have a free ketone (C=O) or free aldehyde (C-OH) group, or a free hemiacetal group.
  • All monosaccharides have reducing ability.
  • The Fehling test is used to detect reducing sugars based on their ability to reduce copper ions (Cu^{2+}). A red precipitate indicates a positive result.. If no reducing sugars are present, the solution remains blue.

Oxidation of Monosaccharides:

  • The aldehyde groups in monosaccharides can be oxidized to carboxylic acid groups.
  • Oxidation of glucose yields gluconic acid.
  • C6H{12}O_6 + Oxidizing Agent \rightarrow Aldonic Acid
  • Mild oxidizing agents like bromine water or Tollens' reagent can be used.

Modifications of Sugars:

  • (1) Phosphate Groups:
    • Phosphate groups are added during glycolysis and are key intermediates in energy generation.
    • Examples: D-glucose-6-phosphate, D-fructose-6-phosphate, D-fructose-1,6-bisphosphate.
  • (2) Adenosine-Triphosphate (ATP):
    • ATP is formed via a N-glycosidic linkage on the anomeric carbon.
  • (3) Amino Sugars:
    • In amino sugars, a hydroxyl group is replaced with an -NH_2 or -NHAc group.
  • (5) Deoxy Sugars:
    • Deoxy sugars are carbohydrates missing a hydroxyl group.
    • Examples: 2-Deoxy-D-ribose, 6-Deoxy-L-Galactose (fucose).

From Monosaccharides to Complex Carbohydrates:

  • Monosaccharides -> Disaccharides -> Oligosaccharides -> Polysaccharides

Linking of Monosaccharides:

  • Monosaccharides are linked together via O-glycosidic bonds.
  • The chemistry of sugar chains depends on the types of sugars and the bonds holding them together.

Disaccharides:

  • Sucrose:
    • Non-reducing disaccharide.
    • Composed of glucose and fructose.
    • O-\alpha-D-glucopyranosyl-(1\rightarrow 2)-\beta-D-fructofuranoside
    • Sucrase/invertase cleaves the bond to yield glucose and fructose, which can then enter ATP production pathways.
  • Maltose:
    • Reducing sugar.
    • Composed of two glucose molecules linked by an alpha 1-4 glycosidic bond.
    • O-\alpha-D-Glucopyranosyl-(\alpha1 \rightarrow 4)-\alpha-D-glucopyranose
    • Maltase cleaves this bond to yield glucose, which can then enter ATP production pathways.
  • Lactose:
    • Reducing sugar.
    • Composed of glucose and galactose linked by a beta 1-4 glycosidic bond.
    • Lactase cleaves this bond to yield glucose and galactose, which can then enter ATP production pathways.
    • Lactose intolerance results from a lack of lactase, making lactose hard to digest.
  • Cellobiose:
    • Reducing sugar.
    • Composed of two glucose molecules linked by a beta 1-4 glycosidic bond.

Polysaccharides:

  • Polymeric oligosaccharides.
  • Starch:
    • Stored glucose in plant cells.
    • Amylose: Unbranched chain arranged in a coiled structure.
    • Amylopectin: Branched structure.
    • Over half of ingested carbohydrates are in the form of starch.
  • Starch Digestion:
    • α-Amylase breaks down starch into oligosaccharides, trisaccharides, and α-dextrins.
    • α-Glucosidase breaks down disaccharides into glucose.
  • Glycogen:
    • Stored glucose in animal cells.
    • \alpha-1,4-Glycosidic bonds with α-1,6-Glycosidic branches
  • Cellulose:
    • Unbranched polymer with beta 1-4 linkages.
    • Forms straight chains called fibrils, which come together via hydrogen bonds to form twined ropes of glucose.
    • Cellulase can break down beta-1,4 glycosidic bonds.

Carbohydrates in Complex with Other Molecules:

Glycoproteins:

  • Carbohydrates covalently attached to a protein.
  • More protein than sugar.
  • Found in the cell membrane for cell-cell signaling and cell adhesion.
  • Many secreted proteins are also glycoproteins.
  • O-linked through serine/threonine.
  • N-linked through asparagine.
  • Carbohydrate chains are shorter and attach to specific amino acid residues.
  • Glycoproteins allow cells to stick together and transmit information due to the diversity in sugar monomers, linkages, and branching.
  • Lectins: Proteins on cell surfaces recognize other proteins based on the specific carbohydrate they carry, forming a lectin-glycoprotein interaction.
    • Selectins are one class of lectins used by immune system cells to anchor at sites of injury for the inflammatory response.
      Role in Nature: E. coli adheres to the digestive system through lectins, and viruses gain entry to host cells by co-opting this system.
  • Blood Type:
    • The role of glycoproteins A, B, and O types due to glycosyltransferase.
  • Antibodies: Glycoproteins found in serum and tissue fluids, produced in response to contact with immunogenic foreign molecules.
    • IgE, IgG, IgM, IgA, and IgD are examples.

Proteoglycans:

  • Complex molecules composed of a core protein and long chains of glycosaminoglycans (GAGs).
  • Essential components of the extracellular matrix.
  • GAGs are long, linear polysaccharides made of repeating disaccharide units (amino sugar and uronic acid).
  • Play crucial roles in maintaining structural integrity, regulating cell signaling, and facilitating interactions between cells and their environment.

Glycolipids:

  • Molecules composed of a lipid (fatty acid) moiety linked to a carbohydrate chain.
  • Found in the cell membrane and are involved in cell recognition, signaling, and adhesion.
  • Contain a hydrophobic lipid tail and a hydrophilic carbohydrate portion.
    Glycosphingolipids: Sphingosine linked to a fatty acid, with a carbohydrate attached.
    Glyceroglycolipids: Glycerol as the lipid component, often found in bacterial and plant membranes.

Lipopolysaccharides (LPS):

  • Large molecules that make up a significant portion of the outer membrane of Gram-negative bacteria.
    Lipid A: A glycolipid that is a hydrophobic anchor embedding into the bacterial outer membrane. It is responsible for endotoxic properties and triggers strong immune responses.
    Core Oligosaccharide: A short chain of sugar molecules that varies between different Gram-negative bacteria.
    O-Antigen: The outermost portion consisting of repeating sugar units, highly variable among bacterial strains, and plays a role in host-pathogen interactions.

Sugar in Structure of Nucleic Acids:

  • Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) are nucleic acids for storage and transmission of genetic information.
  • Nucleotides are composed of a sugar molecule, a phosphate molecule, and a nitrogenous base.
  • Sugar in DNA: Deoxyribose (a five carbon sugar).
  • Sugar in RNA: Ribose (a five carbon sugar).
  • Nitrogenous bases in RNA: Adenine, Uracil, Cytosine, Guanine.
  • Nitrogenous bases in DNA: Adenine, Thymine, Cytosine, Guanine.