Carbohydrates Lecture Notes

Carbohydrates: Introduction

• Major class of biological macromolecules.
• Aldehydes or ketones with multiple -OH (hydroxyl) groups.

Carbohydrates: Terminology and Composition

• Term "carbohydrate" originates from the composition of molecules like glucose (C6H{12}O_6), which can be considered six carbon atoms and six water molecules.
• Simple carbohydrates are monosaccharides containing 3-9 carbon atoms.
• Diversity primarily stems from stereochemical variations around carbon atoms.
• Monosaccharides can link to form longer chains called oligosaccharides.

Glucose: A Key Monosaccharide

• Most common simple carbohydrate (monosaccharide) in nature.
• Hexose (six-carbon sugar).
• Major fuel source for the body, isolated cells, and embryos.
• Plant polymers like starch and cellulose consist of long glucose molecule chains.
• Carbohydrates like glucose are extremely polar, forming many hydrogen bonds with water, hence being very water-soluble.

Roles of Carbohydrates

• Major energy source for cells, especially glucose.
• Animal cells store glucose as glycogen, primarily in the liver and muscle.
• Key components of cellular structures, e.g., ribose and deoxyribose in RNA and DNA.
• Linked to proteins and lipids, mainly in the cell membrane, contributing to:
  • Recognition of signaling molecules.
  • Cellular adhesion.
  • Cell-cell interactions.
• Major constituents of the extracellular matrix in animal cells.

Monosaccharides: Aldoses and Ketoses

• Simple sugars divided into:
  • Aldoses: aldehyde group on carbon one.
  • Simplest aldose: glyceraldehyde.
  • Ketoses: ketone function on an internal carbon (usually carbon two).
  • Simplest ketose: dihydroxyacetone.
• Phosphorylated forms of glyceraldehyde and dihydroxyacetone involved in intracellular glucose oxidation.
• Aldehydes and ketones both have an oxygen atom double-bonded to a carbon atom, but:
  • Ketone: carbon is bonded to two other carbons.
  • Aldehyde: terminal carbon bonds to oxygen and hydrogen.

Stereoisomers of Carbohydrates

• All carbohydrates, except dihydroxyacetone, have one or more asymmetrical carbons.
• Stereoisomers are mirror images (e.g., D-glyceraldehyde and L-glyceraldehyde).
• Physiological form of glyceraldehyde is the D isomer.
• Representing 3D structures on 2D:
  • Solid cones: atoms above the plane.
  • Broken cones: atoms below the plane.
  • Fischer projections: horizontal bonds for groups in front of the plane.

Hexoses

• Six-carbon sugars; D-glucose is most common.
• D-glucose has four asymmetric carbons (carbons 2-5), leading to various isomers with the formula C6H{12}O_6, differing in symmetry at one or more carbons.

Pentoses

• Five-carbon sugars; D-ribose is a major component of RNA.
• Like glucose, ribose is an aldose.

Epimers

• Sugars identical except for configuration at one carbon atom.
• Examples: D-galactose and D-mannose are epimers of glucose (at carbon 4 and 2, respectively).
• D-mannose and D-galactose are not epimers of each other, as they differ at more than one carbon.

D and L Isomers

• Nearly all physiological sugars are D isomers.
• If D or L is not specified, assume it is a D sugar.

Ring Formation

• Glucose mainly exists in a six-membered ring form in solution.
• Oxygen atom connects carbon one and carbon five, forming a hemiacetal.
• Ring structures and open-chain forms are in equilibrium, favoring the pyranose (ring) form.
• Hemiaesthesia formation generates an additional asymmetry center at carbon one.
  • Alpha form: -OH is below the ring plane.
  • Beta form: -OH is above the ring plane.
• Alpha and Beta forms are anomers (interconvertible) rather than isomers (fixed structures), due to equilibrium with a small amount of open-chain aldehyde structure.

Fructose

• Most common ketose in the diet; a six-carbon sugar like glucose.
• Has a keto group on carbon two, unlike glucose (aldehyde group on carbon one).
• Fructose spontaneously forms ring structures, termed furanose for the five-membered ring.

Pentose Rings

• Five-carbon sugars (pentoses) also form furanose rings. The figures show:
  • Ribose: Ring structure formed between the C1 aldehyde and the C4 hydroxyl.
  • Deoxyribose: Lacks the hydroxyl group at the second carbon atom.

Nucleic Acids

• Nucleic acids contain nitrogenous bases held together by long chains polymers of pentose phosphates.
• Pentose in DNA is deoxyribose; RNA contains ribose.
• The absence of an -OH group on deoxyribose's second carbon atom contributes to DNA's greater chemical stability compared to RNA.
• Classic DNA double helix: two chains of deoxyribose phosphate polymer running in opposite directions.
• Chains held by hydrogen bonds between nitrogenous bases:
  • A (adenine) pairs with T (thymine).
  • C (cytosine) pairs with G (guanine).

Modified Monosaccharides

• Modified monosaccharides have substituents that differentiate them from basic carbohydrates.
• Examples:
  • Glucose with a methyl group on carbon six (deoxy sugar).
  • N-acetylgalactosamine and N-acetylglucosamine: amine groups replace hydroxyls on carbon two, further modified by an acetate group (amide linkage).
  • Sialic acid: based on neuraminic acid (nine-carbon sugar derivative) w/ three extra carbons (R).
  • Carboxyl group at carbon one (acidic).
  • Amino sugar with amine group on carbon five.
  • Further modified by acetylation, similar to N-acetylglucosamine.

Reducing Sugars

• Free aldehyde and ketone groups are chemically reactive and can oxidize in solution.
• Sugars like glucose and ribose (in equilibrium with open-chain structures) are reducing sugars, reducing copper ions (Cu2+) to copper (Cu+) in clinical tests.
• The sugar's aldehyde group oxidizes to an acid.

Glycosidic Bonds

• Reactive aldehyde and ketone groups of sugars can form glycosidic bonds with alcohol and amino groups.
• Example: Methanol addition to glucose forms an O-glycosidic bond (alpha or beta form).
• N-glycosidic bond forms if the sugar bonds with a molecule having an amino group.
• The glycosidic bond ties up the anomeric carbon in a covalent bond, preventing the sugar ring from opening and the aldehyde group from reacting. Therefore, the product isn't a reducing sugar.

Complex Carbohydrates

• Formed by linkages between monosaccharides.
• Disaccharides: contain two sugar molecules.
• Glycosidic bond: formed between the aldehyde or ketone group of one sugar molecule and the hydroxyl group of a second molecule.
• Maltose: contains two glucose residues linked head to tail, with the glycosidic bond formed by carbon one of the first glucose and carbon four of the second glucose (alpha-1,4-glycosidic bond). Two hydrogen atoms and one oxygen atom are lost as water.

Formation and Hydrolysis of Glycosidic Bonds

• Formation: Removal of water.
• Breaking: Addition of water (hydrolysis), separating the two sugars.
• Hydrolysis occurs during digestion when disaccharides are broken down into component monosaccharides.

Common Disaccharides

• Sucrose (table sugar): glucose and fructose.
• Lactose (milk sugar): glucose and galactose.
• Enzymes on the luminal surface of small intestine cells split disaccharides into constituent monosaccharides via hydrolysis (adding water).
• Monosaccharides are absorbed and transported in the blood, while cells can only utilize monosaccharides (especially glucose), not disaccharides.
• Sucrose is used in cryopreservation media because it doesn't penetrate cells, preventing excess water entry during thawing.

Glycogen: Animal Glucose Storage

• Animal cells store glucose as glycogen (a homopolymer).
• Major depots: liver (hepatocytes) and muscle; small amounts in nearly all cells.
• Glycogen: long chains of glucose molecules linked by alpha-1,4-glycosidic linkages (like maltose).
• Highly branched polymer with branches approximately every 10 glucose moieties created by alpha-1,6-glycosidic linkages.
• Branching results in a compact molecule for storage within the cell.
• Non-reducing ends on chains prevent aldehyde groups from interacting with other cellular molecules.

Starch: Plant Glucose Storage

• Starch is the energy storage form in plants.
• High content in storage parts (e.g., potato tubers, rice and wheat seeds).
• Similar to glycogen, having alpha-1,4-glycosidic linkages and alpha-1,6 branches, but less branched.
  • Amylose: straight chains without branches.
  • Amylopectin: branches approximately every 30 glucose moieties.
• Starch is readily hydrolyzed by digestive enzymes, a major dietary energy source.

Cellulose: Plant Structural Component

• Major component of cell walls and wood, providing structural strength in plants.
• Chemically different from amylose because glycosidic linkages in cellulose are beta-1,4 rather than alpha-1,4 linkages.
• Polymers form long, straight chains instead of compact granules.
• Humans and most animals lack enzymes to hydrolyze beta-1,4 linkages and cannot digest cellulose.