Comparative study on kinetic properties of bilirubin glucuronidation by UDP-glucuronosyltransferase 1A1

摘要

UDP-glucuronosyltransferase 1A1 (UGT1A1) is the only physiological relevant enzyme in bilirubin glucuronidation. Mutations of the UGT1A1 gene reduce the enzyme activity, leading unconjugated hyperbilirubinemia, such as Gilbert syndrome and Crigler-Najjar syndromes types I and II which are characterized by jaundice. Bilirubin has two sites capable of glucuronidation and forms bilirubin mono- and di-glucuronides (BMG and BDG). In this study, we established the high-throughput quantitative methods for BMG and BDG using UPLC-Orbitrap MS technique, and compared each glucuronidation capacity of the wild and mutated UGT1A1.