Roles of human UDP-glucuronosyltransferases in clearance and homeostasis of endogenous substrates, and functional implications.

Human UDP-glucuronosyltransferases (UGTs) are major phase II enzymes in the drug metabolism system. Despite major advances in characterization of UGT gene family members, their role in clearance and homeostasis of endogenous substrates is insufficiently understood. Endobiotic substrates including bilirubin, serotonin, eicosanoids, steroid hormones, bile acids, thyroxine and fat-soluble vitamins A and D are discussed. Species- and tissue/cell-dependent regulation of UGT expression by ligand-activated transcription factors is often involved in endobiotic homeostasis. However, roles of particular UGTs are often difficult to delineate since they function together with other enzymes and transporters. Better knowledge of endobiotic UGT substrates and consequences of their conjugation may help to understand evolutionary conserved UGT functions.