UDP-glucuronosyltransferases (UGT) represent the major phase II drug metabolism pathway in human. UGT enzymes catalyze the transfer of glucuronic acid (derived from UDPGA co-factor) to xenobiotics and endogenous substrates having nucleophilic acceptor groups, making them more polar and readily excreted in urine or bile. To date, at least 18 human UGT enzymes have been cloned and sequenced. Like the P450 enzymes, UGTs possess broad and overlapping substrate specificities. Clinically relevant drug interactions have been identified for UGT isoforms, leading regulatory agencies (FDA) to require drug interaction testing for compounds showing significant UGT metabolism.
UGT1A8 is solely extra-hepatic, predominantly expressed in the intestinal tract. This enzyme demonstrates a high reactivity towards numerous endogenous and exogenous substrates including dietary and environmental carcinogens and drugs. It is an important UGT for drug glucuronidation in the small intestine.