Paracetamol (acetaminophen) hepatotoxicity in overdose is due to accumulation of which reactive metabolite?
- A Phenacetin
- B Acetaldehyde
- C N-acetyl-p-benzoquinone imine (NAPQI) ✓
- D Trichloroethylene oxide
Correct answer: C. N-acetyl-p-benzoquinone imine (NAPQI)
Explanation
CYP2E1 (and CYP3A4) converts paracetamol to NAPQI, a highly electrophilic reactive metabolite; at therapeutic doses, NAPQI is rapidly detoxified by conjugation with glutathione. In overdose, glutathione stores are depleted, and NAPQI covalently binds hepatocyte proteins (centrilobular necrosis). N-acetylcysteine replenishes glutathione. Phenacetin is the parent compound of paracetamol. Acetaldehyde is the toxic metabolite of ethanol.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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