Biochemistry · Topic

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.

Gout

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.

Add to my cards (4)

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

Sources: Methotrexate: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026); Aspirin: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026); Allopurinol: MedlinePlus Drug Information (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).

← All of biochemistry

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.