UGT1A4 Background Information Glucuronidation, an important bile acid detoxification pathway, is catalyzed by enzymes belonging to the UDP-glucuronosyltransferase (UGT) superfamily. UGT genes are classified into the UGT1A and UGT2B subfamilies. Although each subfamily and each isoform shows tissue-specific patterns of distribution, the underlying mechanisms for this tissue specificity have not been fully elucidated. The human UDP-glucuronosyltransferase 1 (UGT1) locus encodes at least ten UGT1A proteins (UGT1A1-UGT1A10) that play a prominent role in drug and xenobiotic metabolism. Research indicates that nuclear receptors such as pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor (PPAR) can regulate UGTs, which may contribute to the tissue-specific expression pattern of UGTs. Deficiency in the expression and/or activity of UGTs may lead to genetic and acquired diseases such as Crigler-Najjar syndrome and Gilbert syndrome. Based on their ability to catalyze the glucuronidation of xenobiotics and endobiotics, UGTs play a critical role in hormonal homeostasis, energy metabolism, bilirubin clearance and xenobiotic detoxification.
