Paracetamol, also known as acetaminophen, is a widely used analgesic and antipyretic drug. The liver is the primary site for the metabolism of paracetamol. The biotransformation of paracetamol mainly occurs through three major pathways: glucuronidation, sulfation, and oxidation.1. Glucuronidation: This is the primary metabolic pathway for paracetamol, accounting for approximately 50-70% of the drug's metabolism. In this process, paracetamol is conjugated with glucuronic acid to form paracetamol glucuronide. The enzyme responsible for this reaction is UDP-glucuronosyltransferase UGT , specifically the UGT1A1 and UGT1A6 isoforms.2. Sulfation: This pathway accounts for approximately 20-30% of paracetamol metabolism. Paracetamol is conjugated with a sulfate group to form paracetamol sulfate. The enzyme involved in this reaction is sulfotransferase SULT , particularly the SULT1A1 and SULT1A3 isoforms.3. Oxidation: This pathway is responsible for a smaller fraction 5-10% of paracetamol metabolism. In this process, paracetamol is oxidized to form a reactive intermediate, N-acetyl-p-benzoquinone imine NAPQI . The enzyme involved in this reaction is cytochrome P450 CYP , specifically the CYP2E1 and CYP1A2 isoforms. NAPQI is highly reactive and toxic, but under normal conditions, it is rapidly detoxified by conjugation with glutathione GSH to form non-toxic cysteine and mercapturic acid conjugates. This reaction is catalyzed by glutathione S-transferase GST .However, when paracetamol is taken in excessive amounts or when glutathione levels are depleted, NAPQI accumulates and binds to cellular proteins, leading to hepatotoxicity and liver damage. In such cases, the administration of N-acetylcysteine NAC , a precursor of glutathione, can help replenish GSH levels and prevent liver injury.In summary, the liver metabolizes paracetamol primarily through glucuronidation, sulfation, and oxidation pathways, involving enzymes such as UGT, SULT, CYP, and GST. The proper functioning of these pathways is crucial for the safe elimination of paracetamol from the body.