Macromolecules

Macromolecules are large biomolecules built by linking many smaller monomers together. The PMDC MDCAT 2026 syllabus focuses on proteins — their classification by structure and function, the way enzymes act as biological catalysts, and the broad biological importance of proteins in living systems. Expect 2-3 MCQs from this chapter, often blending chemistry with biology.

Classification of Proteins

Proteins are polymers of α-amino acids joined by peptide bonds (–CO–NH–) formed by condensation between the –COOH of one amino acid and the –NH₂ of the next. There are 20 standard amino acids, encoded by the genetic code, and the precise sequence determines the protein's three-dimensional shape and biological function.

Classification by structure

Primary structure

The linear sequence of amino acids joined by peptide bonds. Determined by the gene's mRNA. Sickle-cell anaemia is a primary-structure mutation: glutamic acid → valine at position 6 of β-globin.

Secondary structure

Local folding into α-helix or β-pleated sheet, stabilised by hydrogen bonds between the C=O and N–H groups of the polypeptide backbone.

Tertiary structure

The overall 3-D fold of a single polypeptide chain, stabilised by hydrogen bonds, hydrophobic interactions, ionic bonds, and disulphide (–S–S–) bridges between cysteine residues.

Quaternary structure

Assembly of two or more polypeptide subunits into a functional protein. Haemoglobin (2α + 2β subunits with 4 haem groups) is the textbook example.

Classification by composition

• Simple proteins — yield only amino acids on hydrolysis (e.g. albumin, globulin, keratin).
• Conjugated proteins — contain a non-protein prosthetic group: glycoproteins (sugar), lipoproteins (lipid), nucleoproteins (nucleic acid), metalloproteins, haemoproteins (haem, e.g. haemoglobin).
• Derived proteins — products of partial hydrolysis or denaturation (proteoses, peptones, peptides).

Classification by shape

• Fibrous proteins — long, insoluble in water, structural roles. Examples: collagen (skin, tendon), keratin (hair, nails), elastin, fibroin (silk).
• Globular proteins — spherical, water-soluble, functional/dynamic roles. Examples: haemoglobin, enzymes, antibodies, insulin.

Enzymes as Biocatalyst

Enzymes are biological catalysts — almost all are globular proteins (a few are catalytic RNA, called ribozymes). They speed up biochemical reactions by lowering the activation energy without being consumed and without changing the overall position of equilibrium.

Models of enzyme action

• Lock-and-Key (Fischer, 1894): rigid active site precisely complementary to the substrate — explains specificity but not flexibility.
• Induced Fit (Koshland, 1958): the active site moulds itself around the substrate on binding — the modern accepted view.

Michaelis–Menten kinetics (qualitative)

At low substrate concentration, rate rises almost linearly with [S]. As [S] increases, the rate plateaus at a maximum value V_max when every enzyme molecule is saturated. The substrate concentration at which rate = ½ V_max is called K_m (Michaelis constant) — a low K_m means high affinity for the substrate.

Factors affecting enzyme activity

• Temperature: rate roughly doubles every 10 °C up to an optimum (~37 °C in humans). Above the optimum the protein denatures — tertiary structure unfolds and activity is lost permanently.
• pH: each enzyme has an optimum pH (pepsin ~2, salivary amylase ~6.8, trypsin ~8). Extreme pH alters ionisation of active-site residues and denatures the enzyme.
• Substrate concentration: rate ↑ with [S] until V_max.
• Enzyme concentration: directly proportional to rate (when [S] is in excess).
• Cofactors / coenzymes: required by many enzymes — metal ions (Mg²⁺, Zn²⁺) or organic molecules (NAD⁺, FAD, derived from vitamins).

Inhibition

Competitive inhibition

Inhibitor structurally resembles the substrate and binds the active site. Effect can be reversed by raising [S]. Apparent K_m rises; V_max unchanged. Example: malonate vs succinate at succinate dehydrogenase.

Non-competitive inhibition

Inhibitor binds an allosteric (different) site, distorting the active site. Cannot be reversed by adding more substrate. V_max drops; K_m unchanged. Example: heavy metals (Hg²⁺, Pb²⁺) on enzyme –SH groups.

Importance of Proteins

Proteins are the most functionally diverse biomolecules. Roughly 50 % of the dry mass of cells is protein, and almost every cellular activity depends on one.

Daily requirement and deficiency

An average adult needs ~0.8 g protein per kg body weight per day. Severe deficiency causes kwashiorkor (oedema, swollen belly — protein deficiency with adequate calories) or marasmus (overall energy and protein deficiency, severe wasting).

Worked MCQs

Five MCQs that capture the high-yield testing patterns for this chapter. Read the explanation even when you get the answer right — it's where the deeper concept lives.

Quick Recap

• Proteins = polymers of α-amino acids joined by peptide bonds (–CO–NH–).
• Four structural levels: primary (sequence), secondary (α-helix / β-sheet, H-bonds), tertiary (3-D fold, includes –S–S–), quaternary (multiple subunits, e.g. haemoglobin).
• Fibrous (collagen, keratin) vs globular (haemoglobin, enzymes, antibodies).
• Enzyme cycle: E + S ⇌ ES → E + P. Lower E_a; do not change ΔH or equilibrium.
• K_m = [S] at ½ V_max; low K_m = high affinity.
• Competitive inhibitor ↑ K_m, V_max same; non-competitive ↓ V_max, K_m same.
• Protein deficiency → kwashiorkor / marasmus.