CARBOHYDRATES: INTRODUCTORY BIOCHEMISTRY

General Overview of Carbohydrates

• Definition: Carbohydrates (referred to as “hydrates of carbon”) are organic compounds characterized by empirical formulas of the form
  $ext{(CH}<em>2 ext{O)}</em>n$, where $n ext{ is an integer and } n ext{ is greater than or equal to 3}.$
• Categories of Carbohydrates:
  • Monosaccharides: Single monomeric units.
  • Oligosaccharides: Composed of approximately 2 to 20 monosaccharides.
  • Polysaccharides: Composed of more than 20 monosaccharides.
  • Glycoconjugates: Molecules that consist of carbohydrates linked to proteins or lipids.

Monosaccharides

Aldoses and Ketoses

• Aldoses: Polyhydroxy aldehydes.
• Ketoses: Polyhydroxy ketones.
• Trioses: The smallest monosaccharides, containing three carbon atoms.

Fischer Projections of Monosaccharides

• The structure of monosaccharides can be represented in Fischer projections.
• For aldoses, the aldehyde functionality is drawn at the top (C-1) of the Fischer projection.
• Glyceraldehyde is an aldotriose, distinguished by its chiral center at C-2, which has four different groups attached.
• Dihydroxyacetone is a ketotriose that lacks a chiral carbon and is therefore not chiral.

Monosaccharide Structures: Examples

D-Sugars

• Definition: D-sugars exhibit the same arrangement as D-glyceraldehyde at the chiral carbon furthest from the carbonyl carbon.

• Common D-Aldoses: Includes all monosaccharides with 3 to 6 carbon atoms.

  • Aldotriose (C3): D-Glyceraldehyde.
  • Aldotetroses (C4): D-Erythrose, D-Threose.
  • Aldopentoses (C5): D-Ribose, D-Arabinose.
  • Aldohexoses (C6): D-Glucose, D-Galactose, D-Mannose, etc.

Monosaccharide Characteristics

• Hexoses are the most abundant monosaccharides in nature.
• Aldopentoses serve as critical components of nucleic acids.
• Derivatives of trioses and heptoses are significant intermediates in carbohydrate metabolism.
• All simple monosaccharides are typically crystalline solids, freely soluble in water, and insoluble in nonpolar solvents. Most also taste sweet.

Stereoisomers

• Definition: Stereoisomers have the same molecular formula and structural formula but differ in the spatial arrangement of atoms.
• Optical Isomerism: Exists in molecules with one or more asymmetric carbon atoms (chiral centers).
• All monosaccharides, except for dihydroxyacetone, contain at least one chiral center.
• D- and L-Glyceraldehyde serve as reference compounds for stereoisomer configurations.

Enantiomers

• Definition: Enantiomers are pairs of D-sugars (e.g., D-fructose) and L-sugars, which are mirror images of each other.
• The potential number of optical isomers is represented by the formula $2^n$, where $n$ is the number of asymmetric carbon atoms.
• D-sugars predominate in nature, while L-sugars are less common but do exist, such as L-Fucose and L-Rhamnose.

Epimers

• Definition: Epimers are sugars that differ at only one of several chiral centers.
• Example: D-Mannose and D-Glucose differ at C-2, while D-Galactose and D-Glucose differ at C-4.

Mutarotation and Anomers

• In aqueous solution, many monosaccharides behave as if they possess an additional asymmetric center compared to the open chain form shown in Fischer projections.
• D-Glucose can exist in two forms:
  • α-D-Glucose: Specific rotation $[ ext{α}]_{20} = +112.2°$.
  • β-D-Glucose: Specific rotation $[ ext{α}]_{20} = +18.7°$.
• When dissolved, the optical rotation of both forms changes over time until reaching an equilibrium value of $[ ext{α}]_{20} D = +52.7°.$ The final mixture comprises about one-third α-D-Glucose and two-thirds β-D-Glucose.

Cyclization of Aldoses and Ketoses

• Cyclization occurs when an alcohol reacts with an aldehyde to form a hemiacetal or a ketone to form a hemiketal.
• α-D-Glucopyranose: The result of cyclization of D-Glucose, exhibiting both α and β forms.
• Cyclization of D-Ribose can yield both pyranose and furanose forms.

Carbohydrate Derivatives

Sugar Phosphates

• Monosaccharides can be converted to phosphate esters via a reaction with ATP, serving as important intermediates in metabolic processes.

Deoxy Sugars

• In deoxy sugars, a hydrogen atom substitutes for a hydroxyl group (–OH).
• Most abundant deoxy sugar:
  • 2-Deoxy-D-ribose: Is a vital component of DNA.
• Other important deoxy sugars include L-Fucose and L-Rhamnose, which are components of bacterial cell walls.

Sugar Alcohols

• The carbonyl oxygen of monosaccharides can be reduced (by H₂ gas with metal catalysts or enzymes) to form sugar alcohols, which are polyhydroxy alcohols.
• Sugar alcohols are essential components of lipids.
• Example: FMN (Flavin Mononucleotide) and FAD (Flavin Adenine Dinucleotide).

Sugar Acids

• Definition: Sugar acids are carboxylic acids derived from aldoses.
• Two types of sugar acids have distinct formation pathways:
  1. Aldonic Acids: Formed by oxidation at the carbon at C-1.
  2. Uronic Acids: Formed by oxidation at the highest numbered carbon.
• Example of Aldonic Acid: D-Glucose forms D-Gluconic acid, which plays a role in carbohydrate metabolism.
• Example of Uronic Acid: D-Glucose forms D-Glucuronic acid, a biologically significant compound along with others like D-Galacturonic acid and D-Mannuronic acid.

Reducing Sugars

• Definition: A sugar is a reducing sugar if it has a free aldehyde group or a group that can readily convert into an aldehyde (such as fructose).
• Reducing sugars can act as reducing agents in alkaline solutions, oxidizing to form sugar acids.
• Tests for reducing sugars typically involve cupric ions (Cu²⁺) in a basic solution that yield a visible precipitate when reduced to cuprous ions (Cu⁺) upon reaction.

Amino Sugars

• Definition: An amino group replaces a hydroxyl group in a monosaccharide.
• Difference in structures - For example: D-Glucosamine and D-Galactosamine.
• Significance: Amino sugars are components of glycoconjugates, crucial for various biological functions.
• Structure:
  • Major component of chitin (structural polysaccharide in insect exoskeletons).
  • Found in glycolipids and chondroitin sulfate, vital for cartilage structure.
• Other amino sugars include muramic acid and neuraminic acid, crucial in bacterial cell walls and cell coats of animals, respectively.

Disaccharides and Other Glycosides

Glycosidic Bonds

• Definition: Glycosidic bonds are formed when the anomeric carbon of one monosaccharide reacts with the hydroxyl group of another monosaccharide, forming disaccharides.
• Oligosaccharides and polysaccharides consist of chains of monosaccharides linked by glycosidic bonds.
• Hydrolysis: Glycosidic bonds are broken down by enzymes known as glycosidases, which depend on the type of bond (alpha or beta), the structure of the monosaccharide units, and the specific alcohol involved.

Structure of Disaccharides

• Most prevalent oligosaccharides are disaccharides, with two monosaccharides connected via a glycosidic bond.
• Important factors in disaccharide description:
  • Linking atoms.
  • Configuration of the glycosidic bond.
  • Names of each monosaccharide residue connected.

Maltose Example

• Description: Maltose is formed from two D-Glucose molecules.
• Linked by an α(1→4) glycosidic bond.
• The second glucose has a free anomeric hydroxyl group, allowing for mutarotation.
• Maltose is classified as a reducing sugar.

Cellobiose

• Definition: A repeating disaccharide unit found in cellulose.
• Contains two D-Glucose molecules connected by a β(1→4) glycosidic bond, also undergoes mutarotation and is a reducing sugar.

Lactose

• Description: The prevalent carbohydrate in milk, composed of D-Glucose and D-Galactose linked by a β(1→4) glycosidic bond.
• Lactose undergoes mutarotation and is categorized as a reducing sugar.
• In infants, the intestinal enzyme lactase hydrolyzes lactose into its monosaccharide constituents for absorption.
• In many adults, low levels of lactase result in lactose persistence issues leading to fermentation and discomfort in the gut.

Sucrose

• Description: Commonly known as table sugar, sucrose consists of β-D-Fructose and α-D-Glucose linked by an α,β(1→2) glycosidic bond.
• Unique feature: Unlike many disaccharides, sucrose lacks free anomeric carbons and, thus, does not undergo mutarotation.
• Hydrolysis of sucrose to yield D-Glucose and D-Fructose is referred to as “inversion” and is significantly catalyzed by invertase.

Nucleosides and Other Glycosides

• Anomeric carbons of sugars can connect with alcohols, amines, and thiols, forming glycosidic linkages in suitable solvents.
• Aglycones: Groups attached to anomeric sugar carbon, such as nucleosides linked via a ring nitrogen as seen in guanosine.

Polysaccharides

General Characteristics

• Definition: Polysaccharides (or glycans) are defined by the nature of their recurring monosaccharide units, the chain length, the types of links between units, and the quantity of branching.
• Types:
  • Homoglycans: Comprising one type of monosaccharide.
  • Heteroglycans: Comprising multiple types of monosaccharides.

Classification Based on Biological Roles

• Storage Homoglycans:
  • Starch: Composed of amylose (unbranched) and amylopectin (branched).
  • Glycogen: The primary storage form in animals, more extensively branched than starch.

Structural Homoglycans

• Cellulose: A linear homopolysaccharide featuring β(1→4) linkages. Predominates in plant structures, accounts for significant organic matter.
• Chitin: Composed of N-acetylglucosamine (GlcNAc) linked by β(1→4), essential in arthropod exoskeletons.

Heteroglycans

• Glycosaminoglycans (GAGs): Linear polymers constructed from repeating disaccharide units, characterized by amino sugars and sulfated derivatives, often present in the extracellular matrix.
• Types include:
  • Hyaluronic Acid: Present in connective tissues and synovial fluid; important for lubricant and shock absorption in joints.
  • Chondroitin Sulfate: Key component of cartilage; affected by age or disease states.
  • Keratan Sulfate: Involved in eye and cartilage structures.
  • Heparin: Acts as an anti-coagulant, found in mast cells.

Peptidoglycans

• Structural polysaccharides in bacteria consist of sugar derivatives (GlcNAc and MurNAc) arranged in a grid-like structure, cross-linked by peptides, which are crucial for bacterial cell wall integrity.

Plant and Animal Cell Polysaccharides

• Cells possess outer coats that feature polysaccharides such as glycoproteins, glycolipids, and glycosaminoglycans, important in cellular structure and function.

Conclusion

• This guide offers a comprehensive outline of carbohydrates with a focus on definitions, classifications, and key biochemical features. It serves as a robust resource for understanding the complex roles that carbohydrates play in both biological and biochemical processes.