UDPglucuronosyltransferases

UDP-glucuronosyltransferases (UGTs) are a family of phase II drug-metabolizing enzymes that catalyze the transfer of the glucuronic acid moiety from UDP-glucuronic acid to a wide range of acceptor molecules, a process called glucuronidation. In humans these microsomal enzymes reside primarily in the endoplasmic reticulum of hepatocytes and enterocytes, though they are present in several tissues. The reaction increases the water solubility of lipophilic substances, promoting biliary or renal excretion.

UGTs display substrate diversity and are mainly organized into two large gene families, UGT1A and UGT2B; additional members such as UGT2A and others extend tissue expression. Individual isozymes differ in substrate specificity and kinetics. Common substrates include bilirubin, steroids, estrogens, and a broad range of drugs and xenobiotics. The enzymes require UDP-glucuronic acid as cofactor and typically function as part of the endoplasmic reticulum membrane system.

Genetic variation in UGT genes affects detoxification capacity and drug clearance. Mutations or regulatory polymorphisms of UGT1A1 can cause disorders such as Crigler-Najjar syndrome type I and Gilbert syndrome, illustrating impaired bilirubin glucuronidation. Polymorphisms and expression differences contribute to interindividual differences in drug pharmacokinetics and response. Expression of UGTs is regulated by nuclear receptors and can be induced or repressed by various ligands, including certain drugs and hormones.