Biomolecules — Amino Acids, Proteins, Enzymes, Nucleic Acids

Why Biomolecules Matter

Every living cell is built from four categories of macromolecules: carbohydrates, lipids, proteins, and nucleic acids. Understanding their structure, classification, and function is essential — not just for this chapter, but for genetics, cell biology, and physiology as well. For NEET, this chapter yields 2-3 questions, often on enzyme kinetics, protein structure, or nucleic acid differences.

Protein Structure Hierarchy

flowchart TD
    A[Protein Structure Levels] --> B[Primary - Amino acid sequence]
    B --> C[Secondary - Alpha helix or Beta sheet]
    C --> D[Tertiary - 3D folding of single chain]
    D --> E[Quaternary - Multiple subunit assembly]
    A --> F[Building block: Amino acid]
    F --> G[20 standard amino acids]
    G --> H[Linked by peptide bonds]
    H --> I[Polypeptide chain]
    I --> B

Amino Acids — Building Blocks of Proteins

All amino acids have the same basic structure: a central carbon ( $\alpha$ -carbon) bonded to an amino group (-NH $_2$ ), a carboxyl group (-COOH), a hydrogen, and a variable R group (side chain).

There are 20 standard amino acids in proteins. The R group determines the properties of each amino acid:

Non-polar: Glycine, Alanine, Valine, Leucine, Isoleucine
Polar uncharged: Serine, Threonine, Asparagine, Glutamine
Positively charged: Lysine, Arginine, Histidine
Negatively charged: Aspartate, Glutamate
Special: Cysteine (forms disulphide bonds), Proline (causes kinks)

Amino acids are linked by peptide bonds (between the -COOH of one and -NH $_2$ of the next, with loss of H $_2$ O). A chain of amino acids = polypeptide.

The peptide bond is formed by a condensation reaction (dehydration synthesis). Breaking it requires hydrolysis. Peptide bonds are rigid and planar — this constrains the backbone geometry.

Protein Structure — Four Levels

Primary Structure

The linear sequence of amino acids in the polypeptide chain. Determined by the gene. Changing even one amino acid can alter function (e.g., sickle cell anaemia: Glu → Val at position 6 of the beta chain).

Secondary Structure

Local folding patterns stabilised by hydrogen bonds between backbone atoms.

Alpha helix ( $\alpha$ -helix): Right-handed coil. H-bonds between every 4th peptide bond.
Beta pleated sheet ( $\beta$ -sheet): Flat, zigzag structure. H-bonds between adjacent strands.

Tertiary Structure

The overall 3D shape of a single polypeptide. Stabilised by:

Disulphide bonds (between cysteine residues)
Hydrophobic interactions
Ionic bonds
Hydrogen bonds

Quaternary Structure

Assembly of two or more polypeptide subunits. Example: Haemoglobin has 4 subunits (2 alpha + 2 beta chains). Not all proteins have quaternary structure.

NEET asks about haemoglobin structure regularly. Key facts: quaternary structure, 4 subunits (2 $\alpha$ + 2 $\beta$ ), each subunit has a haem group with Fe $^{2+}$ that binds O $_2$ . Total 4 O $_2$ molecules per haemoglobin.

Enzymes — Biological Catalysts

Enzymes are mostly proteins (some are RNA — called ribozymes) that speed up biochemical reactions by lowering the activation energy. They are not consumed in the reaction.

Properties of Enzymes

Highly specific — each enzyme acts on a specific substrate (lock and key model / induced fit model)
Sensitive to temperature and pH — each enzyme has an optimum
Reusable — not consumed, catalyse many reaction cycles
Work in small amounts

Lock and Key vs Induced Fit

Lock and key model (Fischer): The substrate fits exactly into the enzyme’s active site, like a key into a lock. The active site shape is rigid.

Induced fit model (Koshland): The active site is flexible and moulds around the substrate upon binding. This is the currently accepted model.

Factors Affecting Enzyme Activity

Factor	Effect
Temperature	Activity increases up to optimum (~37°C for human enzymes), then drops sharply (denaturation)
pH	Each enzyme has an optimum pH. Pepsin: pH 2. Trypsin: pH 8. Salivary amylase: pH 6.8
Substrate concentration	Activity increases until all active sites are occupied (V $_{max}$ )
Enzyme concentration	More enzyme = faster reaction (if substrate is not limiting)
Inhibitors	Competitive (bind active site), Non-competitive (bind elsewhere)

V = \frac{V_{max}[S]}{K_m + [S]}

Where:

$V$ = reaction velocity
$V_{max}$ = maximum velocity
$[S]$ = substrate concentration
$K_m$ = Michaelis constant (substrate concentration at which $V = V_{max}/2$ )

Low $K_m$ = high affinity for substrate. High $K_m$ = low affinity.

Students confuse competitive and non-competitive inhibition. Competitive inhibitors resemble the substrate and bind the active site — they can be overcome by increasing substrate concentration. Non-competitive inhibitors bind elsewhere and change the enzyme’s shape — increasing substrate does NOT overcome them.

Carbohydrates

General formula: C $_n$ (H $_2$ O) $_n$ (approximately).

Type	Examples	Function
Monosaccharides	Glucose (C $_6$ H $_{12}$ O $_6$ ), Fructose, Ribose, Deoxyribose	Energy source, nucleic acid components
Disaccharides	Sucrose (glucose + fructose), Lactose (glucose + galactose), Maltose (glucose + glucose)	Transport sugar, dietary sugar
Polysaccharides	Starch, Glycogen, Cellulose, Chitin	Energy storage, structural

Starch = storage in plants (amylose + amylopectin) Glycogen = storage in animals (liver, muscles) Cellulose = structural in plant cell walls (most abundant organic molecule on Earth) Chitin = structural in fungal cell walls and arthropod exoskeletons

Lipids

Not true polymers — they are esters of fatty acids and glycerol (or other alcohols).

Types

Simple lipids (Fats and oils): Glycerol + 3 fatty acids (triglycerides). Saturated fats = solid at room temperature. Unsaturated fats = liquid (oils).
Phospholipids: Glycerol + 2 fatty acids + phosphate group. Form cell membranes (bilayer).
Steroids: Four fused carbon rings. Examples: cholesterol, hormones (testosterone, estrogen, cortisol).

Lipids are the most energy-dense biomolecules — they yield 9 kcal/g (vs 4 kcal/g for carbohydrates and proteins). They also provide insulation and cushioning for organs.

Nucleic Acids

DNA vs RNA

Feature	DNA	RNA
Sugar	Deoxyribose	Ribose
Bases	A, T, G, C	A, U, G, C
Structure	Double-stranded helix	Usually single-stranded
Location	Nucleus (mainly)	Nucleus and cytoplasm
Function	Genetic information storage	Protein synthesis (mRNA, tRNA, rRNA)

Nucleotide Structure

Each nucleotide = nitrogenous base + pentose sugar + phosphate group

Bases:

Purines: Adenine (A), Guanine (G) — two rings
Pyrimidines: Cytosine (C), Thymine (T, in DNA), Uracil (U, in RNA) — one ring

A = T \quad \text{and} \quad G = C

\frac{A + G}{T + C} = 1 \quad \text{(Purines = Pyrimidines)}

These rules hold for double-stranded DNA because of complementary base pairing.

Solved Examples

Example 1 (NEET — Easy)

Q: What type of bond links amino acids in a protein?

A: Peptide bond — formed between the carboxyl group (-COOH) of one amino acid and the amino group (-NH $_2$ ) of the next, with the release of one water molecule (condensation reaction).

Example 2 (NEET — Medium)

Q: If a DNA strand has 30% adenine, what is the percentage of guanine?

A: By Chargaff’s rule, A = T = 30%. Since A + T + G + C = 100%, we get G + C = 40%. Since G = C, G = 20%.

Example 3 (NEET — Hard)

Q: Explain why enzymes lose activity at high temperatures.

A: At high temperatures, the weak bonds (hydrogen bonds, hydrophobic interactions, ionic bonds) that maintain the enzyme’s 3D shape (tertiary structure) are disrupted. The enzyme unfolds — this is called denaturation. The active site loses its specific shape and can no longer bind the substrate. This is usually irreversible.

Common Mistakes to Avoid

Mistake 1: Saying “enzymes are always proteins.” Most enzymes are proteins, but some RNA molecules (called ribozymes) also have catalytic activity. Example: the ribosome itself is a ribozyme — rRNA catalyses peptide bond formation.

Mistake 2: Applying Chargaff’s rules to RNA. Chargaff’s rules (A=T, G=C) apply only to double-stranded DNA. In single-stranded RNA, there is no complementary pairing within the molecule, so A does not equal U.

Mistake 3: Confusing starch and cellulose. Both are polymers of glucose, but starch has alpha-1,4 glycosidic bonds (digestible by humans) while cellulose has beta-1,4 glycosidic bonds (not digestible by humans — we lack the enzyme cellulase).

Practice Questions

Q1. What is the__(?) difference between a cofactor and a coenzyme?

A cofactor is a non-protein component required for an enzyme to function. If the cofactor is an inorganic ion (like Zn $^{2+}$ , Mg $^{2+}$ , Fe $^{2+}$ ), it is called a metal ion activator. If it is an organic molecule, it is called a coenzyme (like NAD $^+$ , FAD, coenzyme A). Coenzymes are often derived from vitamins.

Q2. Why is cellulose not digested by humans but starch is?

Both are glucose polymers, but they differ in glycosidic bonds. Starch has alpha-1,4 linkages that are cleaved by human amylase enzymes. Cellulose has beta-1,4 linkages that require the enzyme cellulase, which humans do not produce. Herbivores like cows can digest cellulose because bacteria in their rumen produce cellulase.

Q3. What are essential amino acids?

Essential amino acids are those that the human body cannot synthesise and must obtain from the diet. There are about 9 essential amino acids in humans: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Deficiency of any one can impair protein synthesis and growth.

Q4. Explain the__(?) difference between fibrous and globular proteins.

Fibrous proteins have elongated, thread-like structures. They are insoluble in water and serve structural roles. Examples: collagen (connective tissue), keratin (hair, nails), actin and myosin (muscle). Globular proteins are spherical, soluble in water, and serve functional roles. Examples: enzymes, antibodies, haemoglobin.

Q5. What is an isoenzyme?

Isoenzymes (isozymes) are different molecular forms of the same enzyme that catalyse the same reaction but differ in structure, amino acid sequence, and physical properties. Example: lactate dehydrogenase (LDH) exists in 5 isoforms found in different tissues (heart, liver, muscle). Their relative levels in blood can indicate which organ is damaged.

FAQs

What is denaturation? Denaturation is the loss of a protein’s 3D structure due to disruption of non-covalent bonds by heat, extreme pH, or chemicals. The primary structure (amino acid sequence) remains intact, but the protein loses its biological activity because the active site shape is altered.

What is the__(?) most abundant protein in the human body? Collagen — a fibrous protein found in connective tissue, bone, cartilage, and skin. It makes up about 25-30% of total body protein.

Why are vitamins important for enzyme function? Many vitamins serve as coenzymes (or precursors to coenzymes) that are essential for enzyme activity. For example, vitamin B $_1$ (thiamine) is a precursor of TPP (thiamine pyrophosphate), a coenzyme for pyruvate dehydrogenase. Without the vitamin, the enzyme cannot function.

What is the__(?) difference between saturated and unsaturated fatty acids? Saturated fatty acids have no double bonds between carbon atoms — the chain is straight and they pack tightly (solid at room temperature, like butter). Unsaturated fatty acids have one or more double bonds that create kinks in the chain, preventing tight packing (liquid at room temperature, like vegetable oil).