Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)

Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a critical Phase II biotransformation enzyme primarily expressed in the liver, where it is localized to the endoplasmic reticulum membrane [1, 4, 17]. It plays a vital role in the detoxification and elimination of both endogenous compounds and exogenous xenobiotics by catalyzing the transfer of a glucuronic acid moiety from UDP-glucuronic acid to lipophilic substrates [1, 3, 9]. This process, known as glucuronidation, significantly increases the water solubility of substrates, facilitating their excretion into bile or urine [1, 9, 17]. UGT1A1 is the only enzyme responsible for the metabolism of bilirubin; genetic deficiencies in its activity lead to hereditary hyperbilirubinemia conditions such as Gilbert syndrome and Crigler-Najjar syndrome [3, 9, 11]. In clinical oncology, UGT1A1 is a major determinant of the metabolism of SN-38, the active metabolite of the chemotherapy drug irinotecan [10, 13, 14, 19]. Patients with reduced UGT1A1 activity, particularly those homozygous for the UGT1A1*28 allele, are at a significantly higher risk for severe, dose-limiting toxicities such as neutropenia and diarrhea [10, 13, 14, 19]. Additionally, UGT1A1 is a target for drug-drug interactions, as several medications like atazanavir and nilotinib can inhibit its function, leading to drug-induced hyperbilirubinemia [6, 10, 11, 13].

Other names

UDP-glucuronosyltransferase 1-1 [3, 4]UDPGT 1-1 [3]Bilirubin-specific UDP-glucuronosyltransferase 1 [3]GNT1 [3]HUG-BR1 [3]UD11 [3, 4]

UGT1A1 functions as a Phase II metabolic enzyme that catalyzes the glucuronidation of substrates by transferring a glucuronic acid moiety from UDP-glucuronic acid to the target molecule, thereby increasing its water solubility and facilitating its excretion from the body [1, 3, 9, 17].