Unit 2: Basic Chemistry of Biomolecules: Carbohydrates, Lipids, Proteins & Amino Acids

Learning Objectives

• Classify carbohydrates, lipids, proteins, and amino acids based on their chemical structure and properties.
• Describe the chemical reactions and optical activity of carbohydrates.
• Differentiate between saponifiable and non-saponifiable lipids, and identify essential fatty acids.
• Explain the organizational levels of protein structure and the macromolecular nature of proteins.
• Discuss the biological and pharmaceutical importance of each class of biomolecules.

Core Content

PART A: CARBOHYDRATES

2.1 Chemistry & Definition

Definition: Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield such compounds upon hydrolysis. They have the general formula Cₙ(H₂O)ₙ (hydrates of carbon).

Chemical Nature:

• Contain carbon, hydrogen, and oxygen.
• Functional groups: Aldehyde (-CHO) or Ketone (-C=O) groups with multiple hydroxyl (-OH) groups.
• The simplest carbohydrates are monosaccharides (e.g., glucose, fructose).

2.2 Classification of Carbohydrates

Based on Carbon Chain Length:

• Trioses (3C): Glyceraldehyde, Dihydroxyacetone
• Tetroses (4C): Erythrose
• Pentoses (5C): Ribose, Deoxyribose
• Hexoses (6C): Glucose, Fructose, Galactose
• Heptoses (7C): Sedoheptulose

2.3 Optical Activity of Carbohydrates

• Definition: The ability of a compound to rotate plane-polarized light.
• Chiral Centers: Carbohydrates contain asymmetric carbon atoms (chiral centers) that give rise to optical isomers.
• D and L Isomers: Based on the configuration of the asymmetric carbon farthest from the carbonyl group:
  • D-isomer: OH group on the right (most naturally occurring sugars).
  • L-isomer: OH group on the left.
• Enantiomers: Mirror-image isomers (e.g., D-glucose and L-glucose).
• Diastereomers: Non-mirror image isomers (e.g., D-glucose and D-mannose).
• Epimers: Differ at only one chiral carbon (e.g., D-glucose and D-galactose at C-4).
• Anomers: Cyclic forms differing at the anomeric carbon (C-1 for aldoses):
  • α-anomer: OH at C-1 is below the ring plane.
  • β-anomer: OH at C-1 is above the ring plane.
• Mutarotation: The change in optical rotation observed when an α or β anomer is dissolved in water and reaches equilibrium (a mixture of both anomers).

2.4 Important Reactions of Carbohydrates

2.5 Biological Importance of Carbohydrates

• Primary Energy Source: Glucose is the main fuel for cellular respiration (ATP production).
• Energy Storage: Glycogen (in animals) and starch (in plants) store glucose.
• Structural Role: Cellulose (plants), Chitin (exoskeleton), and Peptidoglycan (bacterial cell walls).
• Cell Recognition: Glycoproteins and glycolipids on cell surfaces mediate cell-cell interactions and immune responses.
• Nucleic Acid Backbone: Ribose and deoxyribose form the structural framework of RNA and DNA.
• Metabolic Intermediates: Important in the synthesis of other biomolecules.

2.6 Pharmaceutical Importance of Carbohydrates

PART B: LIPIDS

2.7 Chemistry & Definition

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

Chemical Nature:

• Primarily composed of carbon, hydrogen, and oxygen, with occasional phosphorus and nitrogen.
• They are esters of fatty acids with alcohols (e.g., glycerol, cholesterol).

2.8 Classification of Lipids

A. Based on Saponification (Hydrolysis by Alkali)

B. Based on Chemical Composition

2.9 Chemistry of Fatty Acids

Definition: Fatty acids are carboxylic acids with long hydrocarbon chains (usually 4–36 carbons). They are the building blocks of many lipids.

Classification of Fatty Acids:

Essential Fatty Acids (EFA):

• α-Linolenic acid (ALA) – Omega-3 family (18:3)
• Linoleic acid (LA) – Omega-6 family (18:2)
• Arachidonic acid – Conditionally essential (20:4) (can be synthesized from LA)
• Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) – Long-chain Omega-3s (found in fish oil)

2.10 Important Reactions of Lipids and Fatty Acids

2.11 Biological Importance of Lipids

• Energy Source: Most concentrated source of energy (9 kcal/g vs. 4 kcal/g for carbohydrates).
• Energy Storage: Fats stored in adipose tissue are a major reserve fuel.
• Structural Role: Phospholipids and cholesterol form the lipid bilayer of cell membranes.
• Insulation: Subcutaneous fat provides thermal insulation and mechanical cushioning.
• Hormone Precursors: Cholesterol is the precursor for steroid hormones (estrogen, testosterone, cortisol).
• Bile Acid Synthesis: Cholesterol forms bile acids necessary for fat digestion and absorption.
• Fat-soluble Vitamin Carriers: Vitamins A, D, E, K are lipid-soluble and absorbed with dietary fats.
• Eicosanoid Synthesis: Essential fatty acids are precursors to prostaglandins, thromboxanes, and leukotrienes (mediators of inflammation and immunity).

2.12 Pharmaceutical Importance of Lipids

PART C: PROTEINS AND AMINO ACIDS

2.13 Chemistry & Definition

Definition: Proteins are large, complex macromolecules composed of amino acids linked by peptide bonds. They are the most abundant organic molecules in the human body, constituting about 50% of cellular dry weight.

Chemical Nature:

• Contain carbon, hydrogen, oxygen, nitrogen, and often sulfur (in cysteine and methionine).
• Protein molecules are polymers of amino acids joined by peptide bonds (-CO-NH-).
• The diversity of proteins arises from the sequence and arrangement of 20 standard amino acids.

2.14 Classification of Amino Acids

A. Based on R-group Properties (Chemical Nature)

B. Based on Nutritional Requirements (Biosynthetic Capacity)

C. Based on Metabolic Fate (Ketogenic vs Glucogenic)

2.15 Classification of Proteins

A. Based on Shape and Solubility

B. Based on Chemical Composition

2.16 Organizational Levels of Protein Structure

2.17 Macromolecular Nature of Proteins

• Molecular Weight: Proteins range from 5,000 Da (small peptides) to over 1,000,000 Da (large complexes).
• Polymerization: Composed of 50 to several thousand amino acid residues.
• Conformation: Proteins exist in native (functional) and denatured (non-functional) states.
• Biological Activity Depends on Conformation: The specific 3D structure determines function; loss of native conformation (denaturation) leads to loss of biological activity.

Denaturation of Proteins:

• Definition: Disruption of higher-order (secondary, tertiary, quaternary) structure without breaking peptide bonds.
• Agents: Heat, pH extremes, organic solvents, heavy metal ions, detergents.
• Examples: Egg white coagulation on heating; irreversible in most cases.

2.18 Important Reactions of Amino Acids and Proteins

2.19 Biological Importance of Proteins

• Enzymes: Catalyze virtually all biochemical reactions (e.g., DNA polymerase, digestive enzymes).
• Structural Support: Collagen (bone, skin), Keratin (hair, nails), Elastin (elastic tissues).
• Transport: Hemoglobin (O₂ transport), Albumin (fatty acid transport), Transferrin (iron transport).
• Immunological Defense: Immunoglobulins (antibodies) protect against pathogens.
• Hormones and Signaling: Insulin, Glucagon, Growth hormone, Cytokines.
• Movement and Contraction: Actin, Myosin (muscle contraction).
• Gene Regulation: Histones (DNA packaging), Transcription factors.
• Blood Clotting: Fibrinogen, Thrombin.
• Osmotic Balance: Albumin maintains oncotic pressure in blood.
• Buffering: Proteins (e.g., Hemoglobin) act as biological buffers.

2.20 Pharmaceutical Importance of Proteins and Amino Acids

4. Diagrams/Tables

Table 1: Summary of Carbohydrates Classification

                              CARBOHYDRATES
                                    │
            ┌───────────────────────┼───────────────────────┐
            │                       │                       │
     MONOSACCHARIDES          OLIGOSACCHARIDES       POLYSACCHARIDES
        (1 unit)                (2–10 units)            (>10 units)
            │                       │                       │
       - Aldoses              - Disaccharides      - Homopolysaccharides
       - Ketoses              - Trisaccharides     - Heteropolysaccharides
            │                       │                       │
        Glucose                  Sucrose                Starch
        Fructose                 Maltose                Glycogen
        Galactose                Lactose                Cellulose
        Ribose                                          Hyaluronic acid

Table 2: Protein Structure Hierarchy

Diagram 1: Structure of an Amino Acid

        H
        │
H₂N ─── C ─── COOH
        │
        R

R = Variable side chain

Key Groups

• Amino group: -NH₂
• Carboxyl group: -COOH
• α-carbon: Central carbon atom
• R-group: Variable side chain that distinguishes each amino acid

Diagram 2: Peptide Bond Formation

      H₂N ── CH ── COOH   +   H₂N ── CH ── COOH
              │                       │
              R₁                      R₂

                    ↓ Condensation

      H₂N ── CH ── CO ── NH ── CH ── COOH   +   H₂O
              │               │
              R₁              R₂

Peptide bond: -CO-NH-

5. Exam Angle

Short Questions (2-5 marks)

1. Classify carbohydrates with suitable examples.
2. What is optical activity? Explain D and L configuration of sugars.
3. Differentiate between saponifiable and non-saponifiable lipids.
4. List essential fatty acids and their pharmaceutical importance.
5. What is the primary structure of proteins?
6. What is denaturation of proteins? Give causes and examples.
7. Differentiate between glucogenic and ketogenic amino acids.
8. Write the test for tyrosine and cysteine.
9. What are conjugated proteins? Give examples.
10. Differentiate between α-helix and β-pleated sheet.

Long Essays (10+ marks)

1. Classify carbohydrates, describe their chemical reactions, and explain their biological and pharmaceutical importance.
2. Write a detailed note on the classification of lipids and the pharmaceutical importance of lipids.
3. Describe the organizational levels of protein structure. Add a note on the biological and pharmaceutical importance of proteins.
4. Give the classification of amino acids and describe their chemical reactions.

Key Points Frequently Tested

• Carbohydrates: Reducing properties, mutarotation, D/L isomerism.
• Lipids: Essential fatty acids (Omega-3, Omega-6), saponification number, rancidity.
• Proteins: Names and abbreviations of 20 amino acids, denaturation, tests for specific amino acids.
• Clinical correlations: G6PD deficiency (carbohydrate metabolism), hyperlipidemia, protein-energy malnutrition, rheumatoid arthritis (protein biomarkers).

6. Summary Box

• Carbohydrates are polyhydroxy aldehydes/ketones classified as mono-, oligo-, and polysaccharides. They exhibit optical activity and provide energy, structure, and cell recognition.
• Lipids are hydrophobic molecules classified as simple, complex, or derived lipids. Essential fatty acids (Omega-3, Omega-6) must be obtained from the diet. Lipids serve as energy stores, membrane components, and hormone precursors.
• Proteins are macromolecules made of amino acids linked by peptide bonds. There are 20 standard amino acids, classified by R-group properties and nutritional requirements.
• Protein structure has four levels: primary (sequence), secondary (α-helix/β-sheet), tertiary (3D folding), and quaternary (subunit assembly). The native conformation is essential for function.
• All three classes of biomolecules have immense pharmaceutical importance—as drugs, excipients, diagnostic markers, drug targets, and therapeutic agents.

7. References

• Chatterjee, M. N., & Shinde, R. (2011). Textbook of Medical Biochemistry (8th ed.). Jaypee Brothers Medical Publishers.
• Murray, R. K., Bender, D. A., Botham, K. M., Kennelly, P. J., Rodwell, V. W., & Weil, P. A. (2015). Harper's Illustrated Biochemistry (30th ed.). Lange Medical Books / McGraw-Hill Education.
• Nelson, D. L., & Cox, M. M. (2012). Lehninger Principles of Biochemistry (6th ed.). W. H. Freeman.
• Peet, A., Lieberman, M. A., & Marks, A. (2012). Marks' Basic Medical Biochemistry (4th ed.). Lippincott Williams & Wilkins.
• Champe, P. C., & Harvey, R. A. (2013). Lippincott's Illustrated Reviews: Biochemistry (6th ed.). Lippincott Williams & Wilkins.