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.
UGT1A9 shows broad substrate specificity accepting many bulky, non-planar phenolic compounds. UGT1A9 is involved in the glucuronidation of numerous drug substrates. It is abundant in the liver and kidney. Propofol is considered a selective substrate for UGT1A9. Mycophenolic acid has been shown to be predominantly glucuronidated by UGT1A9 in liver tissue.