explain the mode of action of enzymes in terms of an active site, enzyme–substrate complex, lowering of activation energy and enzyme specificity, including the lock-and-key hypothesis and the induced-fit hypothesis

Published by Patrick Mutisya · 14 days ago

Cambridge A-Level Biology – Mode of Action of Enzymes

Mode of Action of Enzymes

Key Concepts

  • Active site – a specialised region on the enzyme where substrate molecules bind.

  • Enzyme–substrate complex (ES complex) – the temporary association of enzyme and substrate(s) during a reaction.

  • Lowering of activation energy (\$E_a\$) – enzymes provide an alternative pathway with a lower energy barrier.

  • Enzyme specificity – each enzyme catalyses only particular reactions or substrates.

  • Lock‑and‑key hypothesis – the active site is a rigid complement to the substrate.

  • Induced‑fit hypothesis – binding of the substrate induces a conformational change in the enzyme, optimising the fit.

Active Site and Enzyme–Substrate Complex

The active site is typically a pocket or groove formed by the three‑dimensional folding of the polypeptide chain. It contains amino‑acid residues that:

  1. Bind the substrate(s) through non‑covalent interactions (hydrogen bonds, ionic bonds, Van der Waals forces).

  2. Orient substrates correctly for the chemical reaction.

  3. Participate directly in the catalytic mechanism (e.g., acting as acid/base catalysts).

When a substrate binds, the enzyme–substrate complex (ES) is formed. This complex is transient; after the reaction, the products are released and the enzyme is regenerated.

Lowering Activation Energy

Enzymes accelerate reactions by decreasing the activation energy required for the transition state. This can be illustrated by the energy profile:

\$\text{Reactants} \xrightarrow{\text{Enzyme}} \text{Transition State} \xrightarrow{\text{Enzyme}} \text{Products}\$

In the presence of an enzyme, the peak representing \$E_a\$ is lower, allowing more molecules to reach the transition state per unit time.

Enzyme Specificity

Specificity arises from the precise three‑dimensional arrangement of residues in the active site. Two main models explain how this specificity is achieved:

Lock‑and‑Key Hypothesis

Proposed by Emil Fischer (1894), this model suggests that the active site is a rigid structure that exactly matches the shape of its substrate, like a key fitting into a lock.

Induced‑Fit Hypothesis

Proposed by Daniel Koshland (1958), this model states that the active site is flexible. Binding of the substrate induces a conformational change in the enzyme, enhancing complementarity and catalytic efficiency.

Comparison of the Two Models

AspectLock‑and‑KeyInduced‑Fit
Active‑site rigidityRigid, pre‑formedFlexible, changes shape on binding
Substrate fitExact geometric fit requiredInitial fit followed by adjustment
Explanation of catalysisOnly accounts for specificityExplains both specificity and rate enhancement
Experimental supportLimited; cannot explain allosteric effectsSupported by X‑ray crystallography showing conformational changes

Overall Reaction Cycle

  1. Enzyme (E) binds substrate (S) → ES complex.

  2. Conformational change (induced fit) aligns catalytic residues.

  3. Transition state is stabilised, lowering \$E_a\$.

  4. Products (P) are formed and released.

  5. Enzyme returns to its original conformation, ready for another cycle.

Suggested diagram: Energy profile of a reaction with and without an enzyme, showing the lowered activation energy in the presence of the enzyme.

Key Points to Remember

  • Enzymes are biological catalysts that are not consumed in the reaction.

  • The active site provides a unique micro‑environment that stabilises the transition state.

  • Specificity is governed by the precise arrangement of amino‑acid residues.

  • Both lock‑and‑key and induced‑fit models contribute to our understanding, but induced‑fit better explains dynamic aspects of catalysis.