Description
Uridine diphospho-glucuronosyltransferases (UGTs, EC 2.4.1.17) are a superfamily of microsomal membrane-bound glycosyltransferase enzymes. UGTs are responsible for the vast majority of Phase II biotransformation (conjugation) reactions, in which a hydrophilic moiety is attached to small molecule drugs and other xenobiotics to facilitate their rapid excretion from the body. UGTs are predominantly expressed in the liver, intestine and kidneys, where they catalyze the addition of a glucuronic acid moiety from the nucleotide sugar uridine-5"-diphospho-α-D-glucuronic acid (UDPGA) to nucleophilic hydroxyl, sulfhydryl or amino groups of pharmacologically active drugs, Phase I drug metabolites and certain endogenous substrates such as steroid hormones, bile acids and bilirubin. Isozymes of the UGT family have extremely broad, often overlapping substrate specificities and tend to exhibit modest affinity for substrates but high catalytic turnover rates. UGTs also contribute to "first-pass" presystemic drug metabolism, which dramatically reduces the oral bioavailability of a number of drugs