{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUGT2B7 is a pivotal phase II drug‐metabolizing enzyme that catalyzes the glucuronidation of an extensive array of endogenous and exogenous substrates—including drugs, environmental chemicals, and steroid hormones—thereby increasing their water solubility and facilitating excretion. Its catalytic activity involves the addition of glucuronic acid to substrates such as estrogens, exemplified by its role in converting compounds into pharmacologically inactive conjugates. Two major variant forms (UGT2B7*1 and UGT2B7*2) have been identified, with marked ethnic variation in allele frequencies. Structural studies have elucidated key residues near the UDP‐glucuronic acid binding domain, suggesting that UGT2B7 employs a serine hydrolase–like catalytic mechanism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of drug metabolism, UGT2B7 is the major isoform involved in the biotransformation of clinically relevant compounds. For instance, it is chiefly responsible for the 3‐ and 6‐glucuronidation of morphine into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), metabolites that not only determine analgesic efficacy but also contribute to adverse effects. In addition, UGT2B7 participates in the metabolism of other therapeutic agents such as diclofenac, where its activity influences the biliary excretion of reactive metabolites, and impacts the pharmacokinetics of mycophenolic acid. Multiple studies have explored polymorphisms within the UGT2B7 gene—including variations in coding regions and promoters—that modulate glucuronidation rates and, consequently, alter drug exposure and response profiles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, genetic variation in UGT2B7 can have significant consequences for patient outcomes. Altered enzyme activity due to polymorphic variants has been associated with variability in morphine metabolite ratios, which may affect both analgesic effectiveness and the risk of adverse central nervous system events—such as those observed in neonates exposed to codeine via breastfeeding. Likewise, in patients treated with nonsteroidal anti-inflammatory drugs like diclofenac, changes in UGT2B7 function have been implicated in idiosyncratic hepatotoxicity. In kidney transplant recipients receiving morphine-based analgesia, UGT2B7 genetic differences have been linked to fluctuations in morphine glucuronidation, suggesting that pharmacogenetic profiling could eventually guide individualized dosing strategies to enhance both efficacy and safety."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "C R Bhasker, W McKinnon, A Stone, et al. 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