Asked by PS
Acetaminophen (Paracetamol or PCM) has 4 fates in the body:
1. Glucuronide conjugation (45-55%): Non-toxic
2. Sulfate conjugation (35-45%): Non-toxic
3. Oxidation to NAPQI (N-acetyl-p-benzo-quione imine) by CYP450 2E1 (5-10%): Toxic
4. Renal excretion (5%)
Under normal conditions, NAPQI is detoxified by conjugation with glutathione. In cases of acetaminophen toxicity, the glucuronide and sulfate pathways are saturated, and more acetaminophen is shunted into NAPQI pathway. This results in depletion of hepatocellular glutathione supplies and NAPQI results in hepatocyte damage and death, clinically leading to acute hepatic necrosis.
N-Acetylcysteine (NAC) provides cysteine for glutathione synthesis and also "thiol" group to form an adduct directly with the toxic NAPQI metabolite.
