Which biotransformation process matures by about 2 months after birth, with immature activity linked to accumulation of a toxic acetaminophen metabolite?

• A. Reduction
• B. Oxidation
• C. Glucuronidation
• D. Glutathione conjugation

Answer: (C)

Glucuronidation is the biotransformation process that matures around two months after birth. In newborns, acetaminophen is mainly eliminated by sulfation, while glucuronidation is still developing. When glucuronidation is immature, more acetaminophen is steered toward the oxidation pathway that makes the toxic metabolite NAPQI. NAPQI is normally detoxified by conjugation with glutathione, but if this detoxification is overwhelmed or glutathione stores are limited, NAPQI can accumulate and cause hepatotoxicity. Once glucuronidation matures, more acetaminophen is safely processed via glucuronidation, reducing the relative formation of the toxic metabolite.