2.2 Enzyme Inhibition and Pathway Control

A competitive inhibitor resembles the normal substrate closely enough to bind to the active site. While it occupies that site, substrate cannot bind. Increasing substrate concentration increases the probability that substrate rather than inhibitor reaches each newly available active site, so competitive inhibition can be reduced. The inhibitor does not need to be converted to product, and its binding may be reversible.

A non-competitive inhibitor binds away from the active site and changes enzyme conformation or catalytic behavior. Some active sites can no longer function effectively, so adding substrate does not restore the lost maximum rate. In strict enzyme kinetics, pure non-competitive inhibition is one case within a wider group of allosteric and mixed effects; at IB level, the central contrast is whether increasing substrate can overcome inhibition.

Penicillin illustrates inhibition applied medically. It interferes with bacterial enzymes that cross-link peptidoglycan during cell-wall construction. Growing susceptible bacteria then form weakened walls and may lyse under osmotic pressure. Human cells lack peptidoglycan walls, which helps explain selective toxicity, although allergies and bacterial resistance remain clinically important.

In end-product inhibition, a product late in a pathway inhibits an enzyme acting near the beginning. When product accumulates, pathway flow slows; when the product is consumed, inhibition decreases and flow rises. This negative feedback avoids wasting substrates and ATP, and prevents potentially harmful accumulation. Inhibiting the first committed step is especially efficient because intermediates are not produced needlessly.

Many feedback-regulated enzymes are allosteric. Their regulatory molecule binds at an allosteric site distinct from the active site. Binding stabilizes a conformation with lower or higher activity. In the threonine-to-isoleucine pathway, accumulated isoleucine inhibits threonine deaminase near the start. The end product therefore adjusts its own production without a conscious cellular decision.

Feedback inhibition is dynamic. It does not permanently switch a pathway off, and the product is not necessarily structurally similar to the initial substrate. A graph of pathway rate against end-product concentration would generally decline, but actual cells integrate several signals: substrate supply, energy status, compartmentalization, gene expression and competing branches can all alter flux.

Some enzymes require non-protein helpers. A cofactor is a helper required for activity and may be an inorganic ion such as Mg²⁺, Zn²⁺ or Fe²⁺. A coenzyme is a small organic helper, often derived from a vitamin. Coenzymes can transfer electrons or chemical groups between reactions and are regenerated rather than used as a fuel in a single pass.

Coenzyme A, made using pantothenic acid (vitamin B5), carries acetyl groups in fatty-acid metabolism and the link reaction. NAD and FAD act as electron and hydrogen carriers in respiration, while NADP serves the analogous carrier role emphasized in photosynthesis. Calling these molecules enzymes is incorrect: they assist protein catalysts but do not provide the active-site structure by themselves.