IB Biology HLEnzymes & MetabolismPaper 1 & 2~15 min read
Enzyme Inhibition
A cell that could only switch enzymes on would be in serious trouble. Inhibitors are the off switch — and they are also how statins lower cholesterol and how penicillin kills bacteria.
📚 What you need to know
An inhibitor is a substance that binds to an enzyme and reduces or stops its activity. Inhibitors can come from inside the cell or from outside it.
Competitive inhibitors resemble the substrate and bind to the active site, competing with the substrate for it.
Non-competitive inhibitors bind to an allosteric site elsewhere on the enzyme. This causes a conformational change that alters the shape of the active site.
Only specific substances, called effectors, bind to an allosteric site, and that binding is reversible.
Raising substrate concentration can overcome a competitive inhibitor, but cannot overcome a non-competitive one.
Statins are competitive inhibitors of the enzyme that synthesises cholesterol, lowering blood LDL.
End-product inhibition is a feedback loop: the end product of a pathway acts as a non-competitive inhibitor of an early enzyme. The example to learn is isoleucine inhibiting threonine deaminase.
Mechanism-based inhibition is irreversible: a substrate analogue forms a covalent bond with the active site. Penicillin is the example.
Two ways to block an enzyme
Both types slow the enzyme down or stop it, but they do it in completely different places.
Competitive inhibition
The inhibitor has a similar shape to the substrate.
It binds to the active site and gets in the way, competing with the substrate for the space.
While the inhibitor is there, the substrate cannot bind, so no enzyme–substrate complex forms.
Binding is reversible, so it is a numbers game: whichever molecule is more concentrated wins more often.
Non-competitive inhibition
The inhibitor binds somewhere else entirely — an allosteric site, usually well away from the active site.
Binding there causes interactions inside the enzyme that lead to conformational changes.
Those changes alter the shape of the active site, so the substrate can no longer bind.
This lasts for as long as the effector stays bound. It is reversible, but adding substrate does not help — the substrate has nowhere to go.
Notice the right-hand active site: it has not been filled, it has been reshaped. The substrate is not competing with anything — it simply does not fit.
Telling them apart from a graph
This is the graph question that appears again and again. Plot rate against substrate concentration for an uninhibited enzyme and for each inhibitor, and the three curves behave differently.
Cover the labels and you can still identify the curves: the one that catches up is competitive, the one that never does is non-competitive.
Reading the curves
Both inhibitors lower the initial rate, so both curves start below the normal one.
With a competitive inhibitor, adding more substrate means substrate molecules are more likely to reach an active site first. Given enough substrate, the inhibitor is displaced and the maximum rate is still reached — and the same total amount of product is eventually formed.
With a non-competitive inhibitor, the active site stays the wrong shape no matter how much substrate you add. The maximum rate is never reached, and less product is formed. In effect the inhibitor has lowered the amount of usable enzyme.
Increasing the concentration of either inhibitor reduces the rate further, and enough of it stops the reaction completely.
Feature
Competitive
Non-competitive
Binding site
The active site
An allosteric site
Shape
Chemically resembles the substrate
Chemically unlike the substrate
Effect on the enzyme
Blocks the active site
Changes the shape of the active site
Adding more substrate
Overcomes the inhibitor
Does not overcome the inhibitor
Maximum rate
Still reached, but later
Never reached
Total product formed
Eventually the same
Less than normal
Statins. Statins lower blood cholesterol by acting as competitive inhibitors. They have a shape similar to the substrate of the enzyme that synthesises cholesterol, so they bind to its active site and block access. Less cholesterol is made, so LDL levels — the “bad cholesterol” linked to atherosclerosis and coronary heart disease — fall.
End-product inhibition
This is the cell’s own thermostat. If a pathway makes too much of its end product, that product itself switches the pathway off.
The end product binds to an allosteric site on an enzyme early in the pathway, acting as a non-competitive inhibitor. Because it binds allosterically, it is also called an allosteric inhibitor. This stops intermediate products piling up.
🧩 The feedback loop, step by step
The pathway runs and the end product accumulates.
End product binds to the allosteric site of the first enzyme in the chain.
The active site changes shape, so no more enzyme–substrate complexes form and the pathway slows.
The cell keeps using up the end product elsewhere, so its concentration falls.
Inhibitor molecules detach, the active site reforms, and the enzyme becomes active again.
The pathway restarts. The loop is continuous, which is why the product never runs out and never floods the cell.
The example to learn: threonine and isoleucine
Bacteria synthesise the amino acid isoleucine from threonine. The enzyme threonine deaminase catalyses the first step of that pathway.
Notice the feedback goes to the first enzyme. Blocking step one stops intermediates accumulating anywhere along the pathway.
This is exactly how a thermostat works. The heating raises the temperature; the temperature switches the heating off; the room cools; the heating comes back on. Nothing decides anything — the output controls the input, and the level stays roughly steady.
Mechanism-based inhibition
Both inhibitors so far were reversible. Some are not.
A substrate analogue is a molecule that can form a covalent bond with the active site. The enzyme treats it like a substrate and modifies it, but the modification produces a reactive group, which forms a stable inhibitor–enzyme complex. The enzyme is now permanently blocked. This is mechanism-based inhibition, and it is irreversible.
Penicillin
Bacterial cell walls are made of peptidoglycans — long molecules of peptides and sugars — held together by cross-links.
🧩 How penicillin kills a growing bacterium
A growing bacterium secretes enzymes called autolysins, which cut small holes in its own cell wall so the wall can stretch.
New peptidoglycan molecules fill the gaps and are joined by cross-links, made by the enzyme DD-transpeptidase.
Penicillin has a structure similar to part of the growing peptide chain, so DD-transpeptidase binds to it.
The enzyme modifies the penicillin, forming a stable enzyme–penicillin complex that permanently blocks the active site.
No new cross-links form, but the autolysins keep cutting holes, so the wall gets weaker and weaker.
Water enters the bacterium by osmosis, and the weakened wall cannot withstand the pressure. The cell bursts — death by lysis.
Why penicillin only works on growing bacteria. Once a bacterium has finished growing, its wall no longer needs to expand: autolysins stop cutting holes and no new cross-links are needed. With nothing to block, penicillin has no effect.
Bacteria can become resistant. A DNA mutation can change the shape of the active site of DD-transpeptidase so penicillin no longer binds well. If that mutation is in a plasmid, it spreads quickly, because bacteria transfer plasmids by conjugation — even between different species.
Worked examples
WE 1
Identify an inhibitor from data
Adding substance X to an enzyme reaction lowers the rate. Increasing the substrate concentration restores the original maximum rate. Identify the type of inhibition and explain your answer. (3 marks)
Step 1: the identification
Substance X is a competitive inhibitor.
Step 2: where it binds
It has a similar shape to the substrate and binds to the active site, competing with the substrate for it.
Step 3: why extra substrate works
At high substrate concentration, substrate molecules are far more likely to reach an active site first, displacing the inhibitor, so the maximum rate is still reached.
Maximum rate restored = competitivethe giveaway is always the maximum rate, not the initial rate — both inhibitors lower that
WE 2
Explain end-product inhibition
Explain how isoleucine regulates its own synthesis in bacteria. (4 marks)
Point 1: the pathway
Isoleucine is made from threonine, and threonine deaminase catalyses the first step.
Point 2: what isoleucine does
As isoleucine builds up, it binds to the allosteric site of threonine deaminase, acting as a non-competitive inhibitor.
Point 3: the effect
The active site changes shape, threonine can no longer bind, and isoleucine production stops.
Point 4: the loop closing
As cells use isoleucine for protein synthesis its concentration falls, inhibitor molecules detach, the active site reforms and production resumes.
A continuous feedback loop that keeps isoleucine at a steady levelsay “allosteric site” and “non-competitive” explicitly — both are marking points
WE 3
Describe mechanism-based inhibition
Using penicillin as an example, describe mechanism-based inhibition. (4 marks)
Point 1: what it is
A substrate analogue forms a covalent bond with the active site, producing a stable inhibitor–enzyme complex, so the inhibition is irreversible.
Point 2: the target enzyme
Penicillin resembles part of the growing peptide chain of the bacterial cell wall, so DD-transpeptidase binds it and is permanently blocked.
Point 3: the effect on the wall
No new cross-links form between peptidoglycan molecules, while autolysins keep making holes, so the wall weakens.
Point 4: the outcome
Water enters by osmosis, the wall cannot withstand the internal pressure, and the cell bursts — death by lysis.
Permanent block on cross-linking, then lysisadd that penicillin only affects bacteria that are still growing — it is a common extension mark
💡 Exam tips
Read graph questions carefully: the maximum rate tells you which inhibitor you are looking at.
Use the exact terms active site, allosteric site, effector and conformational change.
Learn the three named examples: statins (competitive), isoleucine (end-product), penicillin (mechanism-based).
Remember end-product inhibition targets the first enzyme of the pathway.
For penicillin, mention autolysins — most answers leave them out and miss the mark for why the wall weakens.
If asked about resistance, link mutation → changed active site → plasmid → conjugation.
⚠ Common mistakes
Saying a non-competitive inhibitor binds to the active site. It binds to an allosteric site somewhere else.
Saying extra substrate overcomes any inhibitor. Only a competitive one.
Claiming a competitive inhibitor reduces the maximum rate. It reduces the initial rate; the maximum is still reached.
Describing end-product inhibition as competitive. The end product binds allosterically, so it is non-competitive.
Saying penicillin dissolves or breaks the cell wall. It stops new cross-links from being made; the autolysins and osmosis do the damage.
Treating all inhibition as irreversible. Only mechanism-based inhibition is.
That completes Enzymes & Metabolism — enzymes make reactions possible in mild conditions, conditions and concentrations set the speed, pathways string the reactions together, and inhibitors keep the system under control. Up next: Adenosine Triphosphate (ATP), the first page of Cellular Respiration, which is one long metabolic pathway built entirely from the ideas on these seven pages.
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