NAPQI (N-acetyl-p-benzoquinone imine) !

The toxic metabolite of acetaminophen: glutathione neutralises it, but when glutathione runs out it destroys liver cells.

Updated 2026-11-01

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Key facts

Cytochromes P450 (mainly CYP2E1, also CYP3A4 and CYP1A2) make it from a small fraction of acetaminophen.
It is an electrophile: it binds protein cysteines, especially mitochondrial ones.
Glutathione (GSH) conjugates it and it is excreted as cysteine and mercapturic acid derivatives in urine.
When hepatic GSH falls to about 30 % of normal, free NAPQI causes zone 3 necrosis.

N-acetylcysteine restores glutathione and protects best when given early after ingestion.
Fasting, malnutrition and chronic alcohol lower GSH or raise CYP2E1 and make injury easier.
Acetaminophen–protein adducts in blood are being studied as a marker of this toxicity.

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

Which molecule neutralises NAPQI under normal conditions?

Hepatic glutathione, which binds it and makes it harmless.

Which zone of the liver lobule does NAPQI damage first, and why?

Zone 3 (centrilobular): it has more CYP2E1 and less oxygen.

Which enzyme makes most NAPQI?

CYP2E1, with contributions from CYP3A4 and CYP1A2.

Molecules are shown in their neutral form, as the databases deposit them; in the cell the acids and phosphates are ionised.

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

Sources: Acetimidoquinone (CID 39763) (PubChem, NCBI, 2026); Paracetamol ADME (Reactome, 2026); Acetaminophen overdose: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.