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Glucuronidation: UGTs catalyze an SN2 nucleophilic substitution where the substrate's nucleophilic functional group (OH, NH2, SH, COOH) attacks the C1 carbon of glucuronic acid in UDPGA, displacing UDP

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8 When APAP is administered at therapeutic doses under normal physiological conditions, the remaining 5–10% of the drug is metabolized in hepatocytes by cytochrome P450 enzymes such as CYP2E1 and CYP1A2 through phase I enzymatic reactions, resulting in the generation of the toxic reactive metabolite NAPQI (Fig