Question
Compare the lock and key model with the induced fit model of enzyme action. Explain how temperature, pH, and substrate concentration affect enzyme activity. What happens when an enzyme is denatured?
(NCERT Class 11, Biomolecules)
Solution — Step by Step
In this model, the enzyme’s active site has a rigid, fixed shape that perfectly matches the substrate — like a key fitting into a lock.
- The substrate (key) fits exactly into the active site (lock)
- The shape is pre-formed and does not change
- Only the specific substrate can bind — this explains enzyme specificity
Limitation: this model is too rigid. It can’t explain how some enzymes act on slightly different substrates or how binding itself can alter enzyme shape.
The active site is not rigid — it’s flexible. When the substrate approaches, the enzyme changes its shape to accommodate the substrate, like a hand closing around a ball.
- The active site moulds itself around the substrate
- Both enzyme and substrate undergo conformational changes
- This model explains why some enzymes can act on related but not identical substrates
- The conformational change also helps in catalysis — straining the substrate bonds
This is the currently accepted model and better explains experimental observations.
Temperature:
- Activity increases with temperature (more kinetic energy, more collisions)
- Reaches a maximum at optimum temperature (37°C for most human enzymes)
- Beyond optimum, the enzyme denatures — the 3D structure unfolds, active site loses shape, activity drops sharply
pH:
- Each enzyme has an optimum pH where activity is maximum
- Pepsin: pH 2 (stomach). Trypsin: pH 8 (intestine). Salivary amylase: pH 6.8
- Extreme pH changes the ionisation of amino acid residues in the active site, disrupting substrate binding
Substrate concentration:
- At low [S]: rate increases linearly with substrate (first-order kinetics)
- At high [S]: rate plateaus at V_max — all enzyme molecules are saturated (zero-order kinetics)
- The substrate concentration at half V_max is the Michaelis constant (Km) — a measure of enzyme-substrate affinity
Denaturation = loss of the enzyme’s native 3D structure (tertiary/quaternary structure) due to heat, extreme pH, or chemicals. The active site collapses. The enzyme becomes inactive, often irreversibly.
The primary structure (amino acid sequence) remains intact — only the folding is disrupted. Some enzymes can refold (renature) if conditions return to normal, but most cannot.
Why This Works
Enzymes are biological catalysts that lower the activation energy of reactions. They do this by binding substrates in a specific orientation, straining bonds, and providing an optimal microenvironment (correct pH, charge distribution) in the active site.
The induced fit model is better than lock and key because real enzymes are dynamic proteins — X-ray crystallography and NMR studies show clear conformational changes upon substrate binding. Hexokinase, for example, closes around glucose like a clamp, excluding water from the active site to prevent wasteful ATP hydrolysis.
Alternative Method
To remember the factors affecting enzyme activity, use the mnemonic: TPS — Temperature, pH, Substrate concentration. Each gives a characteristic curve: bell-shaped for temperature, bell-shaped for pH, and hyperbolic (Michaelis-Menten) for substrate concentration.
NEET loves graph-based questions on enzyme kinetics. You should be able to identify: (1) the optimum temperature from a bell curve, (2) V_max and Km from a Michaelis-Menten curve, and (3) how competitive vs non-competitive inhibitors change these graphs. Competitive inhibitor: same V_max, increased Km. Non-competitive: decreased V_max, same Km.
Common Mistake
Students often say “enzymes are killed by heat.” Enzymes are not alive — they’re proteins. They are denatured by heat, meaning their structure unfolds. Also, denaturation doesn’t always mean destruction — some enzymes can renature if the temperature drops back to normal. Use precise language: “the enzyme is denatured and loses its catalytic activity.”