UDP-glucuronosyltransferase 1-1 and UDP-glucuronosyltransferase 1-3 (UGT1A1 and UGT1A3)

UDP-glucuronosyltransferase 1-1 (UGT1A1) and UDP-glucuronosyltransferase 1-3 (UGT1A3) are essential Phase II drug-metabolizing enzymes belonging to the UGT1A family, encoded by the UGT1A gene locus [5, 10]. These enzymes are primarily localized in the liver and intestines, where they catalyze the glucuronidation of various lipophilic endogenous and exogenous compounds, transforming them into water-soluble metabolites for excretion [3, 9, 15]. UGT1A1 is the sole enzyme responsible for the metabolism of bilirubin; genetic deficiencies in this enzyme lead to hyperbilirubinemia disorders such as Gilbert syndrome and Crigler-Najjar syndrome [10, 15, 16]. In clinical oncology, UGT1A1 is a critical pharmacogenomic target due to its role in detoxifying SN-38, the active metabolite of the chemotherapeutic agent irinotecan [1, 4, 5]. UGT1A3 complements this activity by metabolizing drugs like ezetimibe and telmisartan, as well as participating in the homeostasis of bile acids such as chenodeoxycholic acid [2, 6, 12]. Genetic polymorphisms, particularly the UGT1A1*28 allele, are associated with significantly reduced enzymatic activity, increasing the risk of severe drug toxicities including life-threatening neutropenia and diarrhea [1, 5, 10].

Other names

Bilirubin-specific UDPGT isozyme 1GNT1HUG-BR1UDPGT 1-1UGT1AUDP-glucuronosyltransferase 1A1UDP-glucuronosyltransferase 1A3UGT1A1UGT1A3

These enzymes catalyze the glucuronidation of lipophilic substrates, such as bilirubin and various drugs, by attaching a glucuronic acid moiety to facilitate their detoxification and subsequent excretion into bile or urine.