5.5 Biomolecules: Carbohydrates, Proteins, Lipids & Nucleic Acids

5.5 Biomolecules: Carbohydrates, Proteins, Lipids & Nucleic Acids

Biomolecules are complex organic compounds synthesized by living organisms that serve as structural components, energy sources, biocatalysts, and genetic blueprints. The study of biomolecules bridges fundamental organic chemistry with biological function and is heavily emphasized in the Pakistan Army Medical Cadet examination.

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Carbohydrates: Classification, Structures & Linkages

Carbohydrates are defined as polyhydroxy aldehydes or polyhydroxy ketones, or substances that yield such compounds upon hydrolysis. Their general empirical formula is $C_x(H_2O)_y$.

Classification of Carbohydrates

1. Monosaccharides: Simple sugars that cannot be hydrolyzed into smaller carbohydrate units. They contain $3$ to $7$ carbon atoms.
   • Aldoses: Contain an aldehyde group (e.g., Glucose, Galactose, Ribose).
   • Ketoses: Contain a ketone group (e.g., Fructose, Ribulose).
   • Ring Structures & Anomers: In aqueous solution, D-glucose cyclizes to form a 6-membered pyranose ring via intramolecular hemiacetal formation between the $C_1$ aldehyde and $C_5$ hydroxyl group. This generates an asymmetric center at $C_1$ (the anomeric carbon), yielding $\alpha$-D-glucose ($-OH$ on $C_1$ pointing down in Haworth projection) and $\beta$-D-glucose ($-OH$ pointing up).
2. Oligosaccharides: Yield $2$ to $10$ monosaccharide units upon hydrolysis.
   • Disaccharides: Sucrose (Glucose + Fructose), Maltose (Glucose + Glucose), Lactose (Glucose + Galactose).
   • Reducing vs. Non-Reducing Sugars: Sugars with a free aldehyde or ketone hemiacetal group at the anomeric carbon reduce Tollens' and Fehling's reagents (e.g., all monosaccharides, maltose, lactose). Sucrose is a non-reducing sugar because the glycosidic bond links the anomeric carbons of both glucose ($C_1$) and fructose ($C_2$), leaving no free aldehyde or ketone group.
3. Polysaccharides: High-molecular-weight polymers yielding hundreds to thousands of monosaccharides upon complete hydrolysis.

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Amino Acids & Protein Architecture

Proteins are high-molecular-weight nitrogenous polymers composed of $\alpha$-amino acids linked by peptide bonds ($-CO-NH-$).

Chemistry of $\alpha$-Amino Acids

An $\alpha$-amino acid contains both an amino group ($-NH_2$) and a carboxylic acid group ($-COOH$) attached to the same $\alpha$-carbon atom: $H_2N-CH(R)-COOH$

Zwitterion Formation & Isoelectric Point ($pI$)

In neutral aqueous solution, the acidic carboxyl group loses a proton while the basic amino group accepts a proton, forming a dipolar ion known as a Zwitterion: $H_3N^+-CH(R)-COO^-$

• Amphoteric Nature: Zwitterions react with both acids (accepting $H^+$ to form a cation) and bases (donating $H^+$ to form an anion).
• Isoelectric Point ($pI$): The specific pH at which an amino acid exists predominantly as a neutral zwitterion with zero net electrical charge. At its $pI$, an amino acid does not migrate in an electric field.

          +H⁺ (Acidic pH < pI)              -H⁺ (Basic pH > pI)
        ──────────────────────►            ─────────────────────►
   H₃N⁺-CH(R)-COOH                   H₃N⁺-CH(R)-COO⁻                  H₂N-CH(R)-COO⁻
       Cationic Form                     Zwitterion                      Anionic Form
     (Migrates to Cathode)             (Net Charge = 0)                (Migrates to Anode)

Levels of Protein Structure

1. Primary Structure: The linear sequence of amino acids linked covalently by amide/peptide bonds. Dictated directly by genetic code.
2. Secondary Structure: Localized spatial folding of the polypeptide backbone stabilized by hydrogen bonding between peptide backbone $N-H$ and $C=O$ groups:
   • $\alpha$-Helix: Right-handed coil with $3.6$ amino acid residues per turn (e.g., keratin in hair).
   • $\beta$-Pleated Sheet: Adjacent polypeptide strands aligned parallel or antiparallel (e.g., fibroin in silk).
3. Tertiary Structure: Overall 3-dimensional globular or fibrous folding of a single polypeptide chain, stabilized by interactions between side chains ($R$-groups):
   • Disulfide bonds ($-S-S-$ covalent bridges between cysteine residues)
   • Ionic bonds / Salt bridges (between $-NH_3^+$ and $-COO^-$)
   • Hydrogen bonds
   • Hydrophobic interactions and Van der Waals forces
4. Quaternary Structure: Spatial arrangement and subunit interaction of multi-chain oligomeric proteins (e.g., Hemoglobin, composed of $2 \alpha$ and $2 \beta$ polypeptide chains with heme prosthetic groups).

Protein Denaturation

Denaturation is the disruption of non-covalent secondary, tertiary, and quaternary structures caused by heat, extreme pH, heavy metal ions ($Pb^{2+}, Hg^{2+}$), or organic solvents. Primary peptide bonds remain intact, but the protein loses its native 3D conformation and biological activity (e.g., coagulation of egg white albumin upon boiling).

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Lipids & Fatty Acid Chemistry

Lipids are a heterogeneous group of hydrophobic organic compounds insoluble in water but soluble in non-polar organic solvents (ether, chloroform, benzene).

Simple Lipids: Triglycerides (Triacylglycerols)

Triglycerides are triesters of glycerol (1,2,3-propanetriol) with three long-chain fatty acid molecules:

• Saturated Fatty Acids: Contain no carbon-carbon double bonds (e.g., Palmitic acid $C_{15}H_{31}COOH$, Stearic acid $C_{17}H_{35}COOH$). Higher melting points; solid at room temperature (Fats).
• Unsaturated Fatty Acids: Contain one or more double bonds (e.g., Oleic acid $C_{17}H_{33}COOH$, Linoleic acid $C_{17}H_{31}COOH$). Lower melting points; liquid at room temperature (Oils).

Chemical Reactions of Lipids

1. Saponification: Alkaline hydrolysis of fats or oils with aqueous $NaOH$ or $KOH$ to yield glycerol and alkali metal salts of fatty acids (Soaps): $\text{Triglyceride} + 3 NaOH \rightarrow \text{Glycerol} + 3 R-COO^-Na^+ \text{ (Soap)}$
   • Saponification Value: The mass of $KOH$ in milligrams required to saponify 1 gram of fat/oil.
2. Hydrogenation (Hardening of Oils): Passing $H_2$ gas through vegetable oils in the presence of finely divided Nickel catalyst at $200^\circ\text{C}$ converts liquid unsaturated oils into solid saturated vegetable ghee: $\text{Vegetable Oil } (Unsaturated) + H_2 \xrightarrow[200^\circ\text{C}]{Ni} \text{Vegetable Ghee } (Saturated)$
3. Iodine Value: The mass of iodine in grams absorbed by 100 grams of fat/oil. Measures the degree of unsaturation.

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Nucleic Acids: DNA, RNA & Genetic Code

Nucleic acids are biopolymers responsible for storing, transmitting, and expressing genetic information. They consist of repeating monomeric units called nucleotides.

Structure of Nucleotides vs. Nucleosides

• Nucleoside: Base $+$ Pentose Sugar
• Nucleotide: Base $+$ Pentose Sugar $+$ Phosphate Group (linked at $C_5'$ of sugar via phosphoester bond).
• Polynucleotide Chain: Nucleotides are joined together by $3',5'$-phosphodiester linkages.

Nitrogenous Bases & Sugar Differences

DNA Double Helix Architecture (Watson-Crick Model)

• Consists of two antiparallel polynucleotide chains ($5' \rightarrow 3'$ and $3' \rightarrow 5'$ direction).
• The sugar-phosphate backbones form the outer structural rails, while nitrogenous bases point inward.
• Complementary Base Pairing:
  • Adenine pairs with Thymine via 2 hydrogen bonds ($A = T$).
  • Guanine pairs with Cytosine via 3 hydrogen bonds ($G \equiv C$).
• Chargaff's Rule: In double-stranded DNA, $[A] = [T]$ and $[G] = [C]$, so total purines equal total pyrimidines ($[A] + [G] = [T] + [C]$).

Types of RNA & Central Dogma

1. Messenger RNA (mRNA): Carries genetic code from nuclear DNA to ribosomes; contains codons.
2. Transfer RNA (tRNA): Cloverleaf 2D shape; delivers specific amino acids to ribosomes during translation via its anticodon loop.
3. Ribosomal RNA (rRNA): Structural and catalytic component of ribosomes.

$\text{Central Dogma: } \text{DNA} \xrightarrow{\text{Replication}} \text{DNA} \xrightarrow{\text{Transcription}} \text{mRNA} \xrightarrow{\text{Translation}} \text{Protein}$