Enzyme Models

The instruction is to use both models, which means each must do explanatory work. A description of two diagrams side by side does not explain an interaction; saying what each model accounts for does.

6 marks. Describe the interaction each model proposes, in sequence, then state what each explains, then what the second adds that the first cannot.

Both models exist to explain the same observation: an enzyme catalyses only one reaction, with one substrate, and will not act on a molecule of a different shape. Any acceptable model must therefore account for specificity in terms of the shape of the active site.

Proposed by Emil Fischer in 1894, the lock-and-key model pictures the active site as a rigid pocket of fixed shape. Only a substrate whose shape is exactly complementary can enter it, in the way a single key fits one lock; when it does, an enzyme-substrate complex forms, the reaction proceeds, the product is released, and the active site is left unchanged and ready to bind again.

The induced fit model retains complementary shape but abandons rigidity. The active site is flexible, and as the correct substrate approaches, the enzyme changes shape slightly so the site moulds around the substrate, producing a closer fit than existed before binding. The enzyme-substrate complex that results is more tightly held, and the strain this places on the substrate’s bonds contributes to lowering the activation energy. After the product is released the active site relaxes to its original shape.

Both models explain specificity, since in each the substrate must be approximately complementary to the active site, and both explain why the enzyme is unchanged and reusable. Only induced fit explains why catalysis occurs rather than merely binding, because the shape change actively distorts the substrate rather than simply holding it; and only induced fit is consistent with the fact that enzymes are flexible protein molecules in constant motion rather than rigid solids.

The induced fit model therefore does not contradict lock-and-key but extends it: the requirement for complementary shape is retained, while the rigidity that made the earlier model inconsistent with protein structure is replaced by a dynamic fit. This is a characteristic pattern in science, where a model is refined by later evidence rather than discarded outright.

Evaluate requires a judgement of worth supported by criteria. Describing both models earns almost nothing; the marks are for stating what makes a model useful, testing each against it, and reaching a conclusion.

5 marks. State your criteria, weigh each model against them with evidence, then give a judgement that follows from the weighing.

A scientific model is useful to the extent that it accounts for the observed evidence, allows accurate predictions, and can be understood and applied. These three criteria — explanatory power, predictive accuracy and accessibility — will be applied to each model in turn.

The lock-and-key model has high accessibility: it is simple, easily diagrammed and immediately explains specificity, competitive inhibition, and why denaturation destroys activity by altering the active site’s shape. Its explanatory power is limited, however. It treats the enzyme as rigid, which is inconsistent with evidence that enzymes are flexible proteins whose conformations shift; it does not explain why binding leads to catalysis rather than merely holding the substrate; and it cannot account for enzymes that act on a range of related substrates, nor for allosteric regulation, where a molecule binding elsewhere on the enzyme alters the active site.

The induced fit model has greater explanatory power on the same evidence: it accommodates enzyme flexibility, explains catalysis as arising from the strain that moulding places on the substrate’s bonds, accounts for enzymes acting on several related substrates, and makes allosteric regulation comprehensible. It is supported directly by X-ray crystallography, which shows the conformation of an enzyme differing between its free and substrate-bound states. Its cost is accessibility: it is harder to draw and to picture, and for the simple case of a single specific substrate it adds complexity without changing the prediction.

Induced fit is the more useful model overall, because usefulness in science is judged first by fit to evidence, and it accounts for observations — enzyme flexibility, the mechanism of catalysis, allosteric regulation — that lock-and-key cannot. Lock-and-key nevertheless retains real value as a teaching model and as a sufficient approximation wherever only specificity needs explaining, which is why both are retained rather than one being discarded. Their relationship illustrates how models are refined: the later model preserved what its predecessor got right, complementary shape, and replaced what the evidence contradicted.