How do enzymes catalyse reactions?

Lecture 4

Enzymes as biological catalysts

Enzymes accelerate chemical reactions in cells without being consumed, allowing life‑sustaining reactions to occur at physiological temperatures.

Activation energy (Ea)

The energy barrier that must be overcome for a reaction to proceed; enzymes lower this barrier.

Transition state

A high‑energy, unstable intermediate between reactants and products; enzymes stabilize this state to speed up reactions.

Free energy change (ΔG)

Determines whether a reaction is thermodynamically favourable; enzymes do not alter ΔG.

Reaction rate vs ΔG

Enzymes increase reaction rate but do not change the overall energy difference between reactants and products.

Active site

A specific region of the enzyme where substrates bind and catalysis occurs; shaped to complement the transition state.

Substrate binding

Substrates bind through non‑covalent interactions such as hydrogen bonds, ionic interactions, and van der Waals forces.

Induced fit model

Substrate binding induces conformational changes in the enzyme, optimizing catalytic interactions.

Proximity effect

Enzymes increase reaction rates by bringing reactants close together.

Orientation effect

Enzymes position substrates in the correct orientation for reaction, reducing entropy barriers.

General acid–base catalysis

Enzyme side chains donate or accept protons to facilitate bond cleavage or formation.

Covalent catalysis

Enzyme forms a temporary covalent bond with the substrate, creating a reactive intermediate.

Metal ion catalysis

Metal ions stabilize charges, orient substrates, or participate in redox chemistry.

Electrostatic catalysis

Charged residues stabilize transition states or reaction intermediates.

Serine proteases

Enzymes that use a catalytic triad (Ser, His, Asp) to hydrolyse peptide bonds.

Catalytic triad

Serine acts as nucleophile, histidine as a base, and aspartate stabilizes histidine.

Oxyanion hole

A pocket in serine proteases that stabilizes the negatively charged transition state.

Enzyme–substrate complex

Temporary association between enzyme and substrate that precedes catalysis.

Transition state analogues

Molecules resembling the transition state bind tightly to enzymes and act as potent inhibitors.

Rate enhancement

Enzymes can accelerate reactions by factors of 10⁶–10¹² through transition state stabilization.

Specificity of catalysis

Enzymes are highly specific for their substrates due to precise structural complementarity.