Acetaminophen NAPQI Toxicity
A simple overview of acetaminophen (Tylenol) toxicity:
Acetaminophen (Tylenol) is typically metabolized into nontoxic products by means of sulfation and glucoronidation (blue and green paths, respectively). A small percentage undergoes metabolism into NAPQI, a TOXIC metabolite, via the CYP enzyme family (red). Typically, NAPQI is converted into a nontoxic compound (purple) via glutathione (GSH), but in the event of a massive overdose of acetaminophen where the sulfation and glucoronidation pathways are saturated and GSH is depleted, the concentration of NAPQI increases leading to hepatocellular damage. By administering N-acetylcysteine (NAC), GSH is replenished and more of the toxic NAPQI is converted into nontoxic metabolites.