Carbohydrate Lecture Notes

Carbohydrates

• Suggested readings:
  • Carbohydrates, pp. 325-333
  • 11.1 Monosaccharides Are Aldehydes or Ketones with Multiple Hydroxyl Groups, pp. 333-337
  • 11.2 Complex Carbohydrates Are Formed by Linkage of Monosaccharides

Introduction to Carbohydrates

• This lecture will examine major carbohydrates, which serve as energy sources and/or cellular building blocks.
• A review of basic structural concepts and terminology is essential for discussing complex macromolecules and understanding carbohydrate metabolism and energy generation in the cell.

Carbohydrates as Biological Molecules

• Carbohydrates are a major class of biological molecules.
• They are aldehyde or ketone compounds with multiple -OH groups.
• The term carbohydrate originates from the chemical composition of molecules like glucose (C6H{12}O6), which can be represented as C6 dot (H2O)6.
• Simple carbohydrates are monosaccharides, containing 3-9 carbons.
• Diversity arises from stereochemical variations around carbon atoms.
• Monosaccharides link to form longer chains called oligosaccharides.

Glucose as a Common Monosaccharide

• Glucose is the most common simple carbohydrate or monosaccharide in nature.
• It is a hexose, having six carbons.
• It is a major fuel source for the body, isolated cells, and embryos.
• Plant polymers like starch and cellulose are composed of long chains of glucose molecules.

Major Roles of Carbohydrates

• Carbohydrates, especially glucose, are a major energy source for many cells.
• Animal cells store glucose as glycogen, primarily in the liver and muscle.
• Carbohydrates are involved in key cellular structures:
  • Ribose and deoxyribose form the backbones of RNA and DNA, respectively.
  • Carbohydrates link to proteins and lipids, especially those in the cell membrane, contributing to membrane functions such as:
    • Recognition of signaling molecules
    • Cellular adhesion
    • Cell-cell interactions
• Carbohydrates are major constituents of the extracellular matrix in animal cells.

Aldoses and Ketoses

• Monosaccharides are divided into aldoses and ketoses.
• Aldoses have an aldehyde group on carbon 1.
• The simplest aldose is glyceraldehyde, with carbon 1 (the aldehyde carbon) at the top in conventional drawings.
• Ketoses have a ketone function on one of the internal carbons, typically carbon 2.
• The simplest ketose is dihydroxyacetone.
• Phosphorylated forms of glyceraldehyde and dihydroxyacetone are seen in the intracellular oxidation pathway of glucose.
• Aldehydes and ketones have an oxygen atom double-bonded to a carbon atom, but ketones have this carbon bound to two other carbons, while aldehydes have the terminal carbon bearing oxygen and hydrogen.

Asymmetrical Carbons and Stereoisomers

• All carbohydrates (except dihydroxyacetone) have one or more asymmetrical carbons.
• Glyceraldehyde has two stereoisomers.
• Carbohydrate stereoisomers are mirror images, similar to amino acids.
• The physiological form of glyceraldehyde is the D isomer.
• Different methods depict the 3D structure of asymmetrical carbons on a 2D surface.
• Solid cones connect atoms/groups above the plane, and broken cones for those below the plane.
• Easier stick diagrams (Fisher projections) use horizontal bonds for groups in front of the plane.

Hexoses and Pentoses

• Hexoses are six-carbon sugars.
• D-glucose is the most common hexose in nature and is an aldose sugar.
• Glucose has four asymmetric carbons (carbons 2-5), resulting in many isomers with the same chemical composition (C6H{12}O_6) but different symmetry at one or more carbons.
• Pentoses are five-carbon sugars.
• D-ribose is a pentose sugar and a major component of RNA.
• Like glucose, ribose is an aldehyde sugar or aldose.

Epimers

• Epimers are sugars that are identical except for the configuration at one carbon atom.
• D-galactose and D-mannose are two epimers of glucose commonly found in complex cellular and extracellular oligosaccharides.
• Both are hexoses and aldoses.
• D-mannose differs from D-glucose at C-2, and D-galactose differs at C-4.
• D-mannose and D-galactose are not epimers of each other since they differ at more than one carbon.
• Nearly all physiological sugars are D isomers; an unlabeled sugar name implies it is a D sugar.

Ring Formation of Glucose

• Glucose primarily exists in a six-membered ring form in solution, although straight chains are easier to visualize.
• An oxygen atom connects carbon-1 and carbon-5, forming a hemiacetal.
• A hydrogen atom moves, but the overall chemical composition remains unchanged.
• Ring structures and open chain forms are present in solution, with equilibrium favoring the ring (pyranose) form.

Anomers

• Hemiacetal formation generates an additional center of asymmetry at carbon-1.
• The two configurations are  (-OH below the plane of the ring) and  (-OH above the plane).
• These forms are anomers rather than isomers because isomers have fixed structures, while anomers are interconvertible.
• Interconversion occurs because both are in equilibrium with a small amount of open chain or aldehyde structure.

Fructose

• Fructose is the most common ketose in our diet.
• It is a hexose sugar with six carbons.
• It has a keto group on carbon-2 rather than an aldehyde group on carbon-1 (unlike glucose).
• Fructose spontaneously forms ring structures; the term furanose is used for the five-membered ring.

Pentose Rings

• Pentoses (five-carbon sugars) also form furanose rings.
• Ribose and deoxyribose form ring structures.

Nucleic Acids

• Nucleic acids contain nitrogenous bases held together by long chains (polymers) of pentose phosphates.
• DNA contains deoxyribose, while RNA contains ribose.
• The absence of an -OH group on C-2 of deoxyribose contributes to the greater chemical stability of DNA compared to RNA.

DNA Double Helix

• The classic DNA double helix is formed by two chains of deoxyribose-phosphate polymer running in opposite directions.
• The chains are held together by specific hydrogen bonds between nitrogenous bases.
• The four nitrogenous bases are abbreviated A, C, G, and T:
  • A pairs with T
  • C pairs with G

Modified Monosaccharides

• Basic carbohydrates are all Cx(H2O)_x.
• Modified monosaccharides have one or more substituents to this basic structure.
• Examples:
  • Fucose has a methyl group at carbon-6; it is a deoxysugar because it lacks one hydroxyl group.
  • N-acetyl-galactosamine and N-acetylglucosamine have amine groups instead of hydroxyls on carbon-2; these are further modified by an acetate group.
  • The bond between the amine group and the carboxyl of the acetate is an amide linkage, similar to peptide bonds.

Sialic Acid

• Sialic acid is a complex example based on neuraminic acid, a nine-carbon sugar derivative.
• The extra three carbons are denoted as –R.
• It is an acid due to the carboxyl group (–COO-) at carbon-1.
• It is also an aminosugar, with the amine group on carbon-5.
• Neuraminic acid is further modified by acetylation, similar to N-acetylglucosamine.

Reducing Sugars

• Free aldehyde and ketone groups are chemically reactive and can be oxidized in solution.
• They are called reducing sugars because they can reduce Cu^{+2} (cupric) ions (and other oxidizing agents).
• In the process, Cu^{+2} is reduced to Cu^{+}$(cuprous).
• Hemiacetal and hemiketal ring forms are in equilibrium with open-chain structures, so sugars like glucose and ribose are reducing sugars.
• The aldehyde group of the sugar is oxidized to an acid.

Glycosidic Bonds

• The reactive aldehyde and ketone groups of sugars can form glycosidic bonds with alcohol and amino groups.
• Example: Addition of methanol to glucose forms an O-glycosidic bond.
• The O-glycosidic bond has two stereoisomers: the α and β form.
• If the sugar bonded with a molecule having an amino rather than a hydroxyl group, it would form an N-glycosidic bond.
• The glycosidic bond ties up the anomeric carbon (former aldehyde) in a covalent bond, preventing the sugar ring from opening into a straight-chain form.
• The aldehyde group is no longer free to react with other molecules (such as Cu^{+2} ions), and the product is not a reducing sugar.

Complex Carbohydrates

• Complex carbohydrates are formed by linkages between monosaccharides.
• Disaccharides contain two sugar molecules.
• A glycosidic bond forms between the aldehyde (or ketone) group of one sugar and the hydroxyl group of another.
• Maltose contains two glucose residues linked head-to-tail.
• Two hydrogen atoms and one oxygen atom are removed as a water molecule in the process.
• The notation C-1 → C-4 indicates that the glycosidic bond is formed by carbon-1 of the first glucose being linked to carbon-4 of the second glucose.
• If the oxygen of the glycosidic bond is below the rings of the sugars, this is an α-linkage.

Formation and Breaking of Glycosidic Bonds

• Formation of a glycosidic bond between two sugars (monosaccharides) involves the removal of water.
• Breaking the glycosidic bond involves adding water and separating the two sugars (hydrolysis).
• Hydrolysis occurs during digestion when disaccharides are broken down to their component monosaccharides.

Common Disaccharides

• Sucrose and lactose are common components of the human diet.
• Both contain a glucose molecule and a second monosaccharide.
• Enzymes on the luminal surface of small intestine cells split these disaccharides into their constituent monosaccharides (hydrolysis).
• The monosaccharides are then absorbed and transported in the blood.
• Cells can take up and oxidize monosaccharides (especially glucose) but not disaccharides; sucrose added to culture medium would not be utilized.
• Embryologists use sucrose in cryopreservation media because it does not penetrate the cells, preventing excess water from entering during thawing.

Glycogen

• Animal cells store glucose as a polymer called glycogen (a homopolymer since all monosaccharides are the same).
• Major depots are in liver (hepatocytes) and muscle, but small amounts are found in nearly all cells.
• Glycogen consists of long chains of glucose molecules linked together with α-1,4 glycosidic linkages (like maltose).
• Glycogen is a highly branched polymer, with branches approximately every 10 glucose moieties along each chain (branches have branches!).
• Branches are created by α-1,6 glycosidic linkages.
• The branched structure provides a compact molecule for storage within the cell.
• All aldehyde groups are tied up in glycosidic linkages, leaving non-reducing ends to the chains, making glycogen relatively inert and less likely to interact with other cellular molecules.

Plant Glucose Polymers

• Plants form two types of glucose polymers:
  • Starch: Used for energy storage by the plant.
  • Storage parts of plants (tubers of potatoes, seeds of rice and wheat) have relatively high starch content.
  • Starch is similar to glycogen in having α-1,4 glycosidic linkages and α-1,6 branches but is less branched.
  • Amylose consists of straight chains without any branches.
  • Amylopectin has branches approximately every 30 glucose moieties.
  • Starch is readily hydrolyzed by digestive enzymes and is a major source of energy in the human diet.
  • Cellulose: A glucose homopolymer.
  • A major component of cell walls (and wood), providing structural strength for the plant.
  • The difference between cellulose and the unbranched chains of amylose is that the glycosidic linkages in cellulose are β-1,4 rather than α-1,4.
  • The polymers form long straight chains rather than compact granules.
  • Humans (and most animals) lack enzymes that can hydrolyze the β-1,4 linkages in cellulose and therefore cannot digest it.