Acetylsalicylic acid ASA , commonly known as aspirin, is a widely used nonsteroidal anti-inflammatory drug NSAID that has analgesic, antipyretic, and anti-inflammatory properties. The liver plays a crucial role in the metabolism of aspirin, and the process involves several metabolic pathways and metabolites.1. Hydrolysis: The primary metabolic pathway for aspirin in the liver is hydrolysis. Aspirin is an ester, and it undergoes hydrolysis by esterases, primarily carboxylesterase 1 CES1 , to form salicylic acid SA and acetic acid. Salicylic acid is the primary active metabolite responsible for the therapeutic effects of aspirin.2. Conjugation: After hydrolysis, salicylic acid undergoes further metabolism through conjugation reactions. There are two main conjugation pathways: a. Glycine conjugation: Salicylic acid reacts with glycine to form salicyluric acid, which is catalyzed by the enzyme glycine N-acyltransferase GLYAT . Salicyluric acid is a major urinary metabolite of aspirin. b. Glucuronidation: Salicylic acid can also be conjugated with glucuronic acid, forming salicyl acyl glucuronide and salicyl phenolic glucuronide. This reaction is catalyzed by uridine diphosphate glucuronosyltransferases UGTs , particularly UGT1A1 and UGT1A6. These glucuronide conjugates are excreted in the urine.3. Oxidation: A minor metabolic pathway of salicylic acid is oxidation, which occurs in the liver through the action of cytochrome P450 enzymes, mainly CYP2E1. This reaction forms 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid, which can be further metabolized or excreted in the urine.In summary, the liver metabolizes aspirin primarily through hydrolysis to form salicylic acid, which then undergoes conjugation reactions to form salicyluric acid, salicyl acyl glucuronide, and salicyl phenolic glucuronide. A minor pathway involves the oxidation of salicylic acid to form 2,3-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid. These metabolites are eventually excreted in the urine.