UDP-glucuronosyltransferase 1-7 (UGT1A7)

Human UDP-glucuronosyltransferase 1-7 (UGT1A7) is a phase II drug-metabolizing enzyme primarily expressed in extrahepatic tissues such as the gastrointestinal tract, lungs, and pancreas [1, 11, 12]. It plays a critical role in the detoxification of various xenobiotics, including environmental carcinogens like polycyclic aromatic hydrocarbons, and the metabolism of endogenous compounds such as estrogens and fatty acids [1, 3, 11]. UGT1A7 is particularly notable for its involvement in the glucuronidation of SN-38, the active metabolite of the chemotherapeutic agent irinotecan [1, 10, 14]. Genetic polymorphisms in the UGT1A7 gene, such as the UGT1A7*3 allele, are associated with reduced enzymatic activity, which can lead to an increased risk of severe drug-induced toxicities like neutropenia and diarrhea [10, 14]. Furthermore, these low-activity variants have been linked to an increased susceptibility to certain cancers, including pancreatic and colorectal cancer, due to impaired detoxification of carcinogens [11]. Understanding UGT1A7 function and its genetic variability is essential for personalizing medicine and predicting adverse drug reactions [7, 10].

Other names

UDP-glucuronosyltransferase family 1 member A7UDPGT 1-7UGT1.7UGT1GhUG-BR1

Drugs interact with UGT1A7 either as substrates for glucuronidation or as inhibitors of its enzymatic activity. Substrates are conjugated with glucuronic acid to increase water solubility for excretion, while inhibitors like erlotinib and gefitinib block this process, potentially leading to increased levels of co-administered drugs or toxic metabolites.