C1.1 Enzymes and metabolism

If the chemical reactions of life ran at their natural, unaided speed, you would not survive a single second — many would take years to complete. Enzymes are the biological catalysts that solve this problem, speeding up reactions by factors of millions while remaining unchanged themselves. For C1.1 the central idea is that an enzyme’s power comes from the precise three-dimensional shape of its active site, and that anything affecting this shape — temperature, pH, or an inhibitor — affects how well the enzyme works. Master the link between structure and function and the rest of the topic follows.

How enzymes work: active site and induced fit

An enzyme is a globular protein that acts as a catalyst — it speeds up a specific reaction by lowering its activation energy (the energy barrier that must be overcome for a reaction to proceed) without being used up. Each enzyme has a region called the active site, a pocket whose shape and chemistry are complementary to a particular substrate. Because the fit is so specific, most enzymes catalyse only one reaction or one type of reaction — this is enzyme specificity.

The substrate binds to the active site to form an enzyme–substrate complex. The older lock and key picture treated the active site as a rigid shape, but the syllabus uses the more accurate induced-fit model: the active site changes shape slightly as the substrate binds, moulding around it. This better fit strains the substrate’s bonds and helps to lower the activation energy, after which the products are released and the unchanged enzyme is free to bind another substrate.

Factors affecting the rate of enzyme activity

Because activity depends on the active site’s shape and on collisions between enzyme and substrate, several factors influence the rate:

• Temperature: raising the temperature increases kinetic energy, so enzyme and substrate collide more often and rate rises — up to an optimum. Beyond this, the enzyme begins to denature: bonds holding its tertiary structure break, the active site loses its shape, and activity falls sharply.
• pH: each enzyme has an optimum pH at which its active site shape is ideal. Values far from the optimum disrupt the bonds maintaining the active site and can denature the enzyme. Pepsin works best in the acidic stomach, while many other enzymes prefer near-neutral pH.
• Substrate concentration: rate increases with substrate concentration until the enzymes become saturated — all active sites are occupied — after which adding more substrate has no further effect and the rate plateaus.

Denaturation is generally irreversible; cooling a heat-denatured enzyme does not restore its function, a point examiners frequently check.

Enzyme inhibition

Enzyme activity can be reduced by inhibitors, and the syllabus distinguishes two types by where they bind:

• Competitive inhibitors have a shape similar to the substrate and bind to the active site itself, blocking the substrate. Their effect can be overcome by adding more substrate, because substrate and inhibitor compete for the same site.
• Non-competitive inhibitors bind to a different site (an allosteric site), changing the enzyme’s overall shape so the active site no longer fits the substrate. Adding more substrate does not relieve this inhibition.

This principle underlies end-product inhibition, a key way cells control metabolism: the final product of a pathway acts as a non-competitive inhibitor of an enzyme earlier in the pathway, switching off its own production when enough has accumulated. This is an example of negative feedback.

Metabolism: pathways, anabolism and catabolism

Metabolism is the sum of all the enzyme-catalysed reactions occurring in an organism. These reactions are organised into metabolic pathways — ordered chains or cycles of reactions in which the product of one step is the substrate of the next, with each step controlled by its own enzyme.

Metabolic reactions fall into two complementary groups. Anabolism is the building of large, complex molecules from smaller ones — for example, joining amino acids to form proteins by condensation reactions; it requires energy. Catabolism is the breaking down of large molecules into smaller ones — for example, hydrolysis of polysaccharides into sugars, or respiration of glucose; it releases energy. Together, anabolism and catabolism allow the cell to grow, repair itself and harness energy, all under precise enzyme control.