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# Types of enzyme inhibition

Many drugs and poisons work by slowing an enzyme; depending on where they bind, they change Km, Vmax or both, which shows on the Lineweaver–Burk plot.

Updated 2026-11-01

## Key facts

- Competitive: the inhibitor resembles the substrate and occupies the active site. Km rises, Vmax unchanged; overcome by more substrate. Lines cross on the Y axis.
- Non-competitive: the inhibitor binds another site, on E or ES equally. Vmax falls, Km unchanged; not overcome by substrate. Lines cross on the X axis.
- Uncompetitive: the inhibitor binds only the ES complex. Km and Vmax both fall; the lines are parallel.
- Irreversible: the inhibitor binds covalently (aspirin on COX, organophosphates on acetylcholinesterase); activity returns only when new enzyme is made.
- Suicide inhibitor: the enzyme turns it into a reactive compound that inactivates the enzyme (5-fluorouracil on thymidylate synthase).

## In detail

- Competitive examples: methotrexate on dihydrofolate reductase, statins on HMG-CoA reductase, ACE inhibitors on angiotensin-converting enzyme.
- In methanol or ethylene glycol poisoning, ethanol and fomepizole compete for alcohol dehydrogenase and prevent toxic metabolites from forming.
- Mixed inhibition changes Km and Vmax in different directions; the lines cross away from the axes.
- Plot shortcut: if the Y-intercept moves, Vmax changed; if the X-intercept moves, Km changed.
- Allopurinol is converted to oxypurinol, which binds xanthine oxidase very tightly and lowers uric acid production.
- Organophosphates (pesticides) phosphorylate the active-site serine of acetylcholinesterase: acetylcholine builds up (cholinergic crisis). Oximes can reactivate the enzyme if given before the bond “ages”.
- Feedback: the end product of a pathway inhibits its first enzyme (for example, cholesterol slows its own synthesis).

## Memory aid

“Competitive: Km up, Vmax same — Non-competitive: Vmax down, Km same”.

**Also called**
Competitive inhibition, Non-competitive inhibition, Irreversible inhibition

## Clinical notes

- Aspirin's effect on platelets lasts their whole life span (about 7–10 days) because platelets cannot make new COX.
- Organophosphate poisoning is common in farming areas of Latin America; its basis is irreversible inhibition of acetylcholinesterase.
- Leucovorin (folinic acid) rescue supplies reduced folate beyond the dihydrofolate reductase step blocked by methotrexate.

## Related conditions

- [Gout](https://durgical.com/en/conditions/gout/)

## Related

- [Enzyme kinetics (Michaelis–Menten and Lineweaver–Burk)](https://durgical.com/en/biochemistry/topics/enzyme-kinetics/)
- [Allosteric and covalent regulation of enzymes](https://durgical.com/en/biochemistry/topics/allosteric-and-covalent-regulation-of-enzymes/)
- [Dihydrofolate reductase (DHFR)](https://durgical.com/en/biochemistry/enzymes/dihydrofolate-reductase/)
- [HMG-CoA reductase](https://durgical.com/en/biochemistry/enzymes/hmg-coa-reductase/)
- [Cyclooxygenase (COX-1 and COX-2)](https://durgical.com/en/biochemistry/enzymes/cyclooxygenase/)
- [Xanthine oxidase](https://durgical.com/en/biochemistry/enzymes/xanthine-oxidase/)
- [Thymidylate synthase](https://durgical.com/en/biochemistry/enzymes/thymidylate-synthase/)
- [Angiotensin-converting enzyme (ACE)](https://durgical.com/en/biochemistry/enzymes/angiotensin-converting-enzyme/)

## Test yourself

Think of the answer, then tap the question to see it.

## What happens to Km and Vmax with a competitive inhibitor?

Apparent Km rises and Vmax is unchanged: enough substrate displaces the inhibitor.

## On a Lineweaver–Burk plot, where do the lines of non-competitive inhibition cross?

On the X axis (same −1/Km); the Y-intercept rises because Vmax falls.

## Why does aspirin's antiplatelet effect last for days?

It irreversibly acetylates COX-1, and the platelet, having no nucleus, cannot make new enzyme.

## Which type of inhibition gives parallel lines on a Lineweaver–Burk plot?

Uncompetitive: the inhibitor binds only the ES complex and lowers Km and Vmax in the same proportion.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Methotrexate: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682019.html) (MedlinePlus, US National Library of Medicine, 2026); [Aspirin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682878.html) (MedlinePlus, US National Library of Medicine, 2026); [Allopurinol: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682673.html) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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