UDPglukuronosyltransferaser

UDP-glucuronosyltransferases (UGTs) are a family of phase II detoxification enzymes that catalyze the transfer of glucuronic acid from UDP-glucuronic acid to a wide range of substrates. This glucuronidation reaction produces glucuronides that are generally more water-soluble and less active, facilitating elimination in bile or urine.

In humans, the UGT superfamily is organized mainly into two gene clusters, UGT1 and UGT2, encoding multiple isoforms such as UGT1A1, UGT1A6, and UGT2B7. These enzymes are predominantly expressed in the liver but are also found in other tissues including the intestine, kidney, and, to a lesser extent, the brain. Substrates include bilirubin, steroid hormones, and numerous drugs and xenobiotics, making UGTs central to the metabolism and clearance of both endogenous compounds and foreign chemicals.

Genetic variation in UGT genes influences individual drug responses and disease risk. For example, polymorphisms in UGT1A1 can reduce glucuronidation and contribute to Gilbert syndrome, a mild unconjugated hyperbilirubinemia. Variants in other UGTs can affect the metabolism and toxicity of chemotherapeutic agents such as irinotecan, illustrating the clinical relevance of these enzymes.

UGTs are regulated by nuclear receptors such as PXR and CAR and can be induced by drugs like phenobarbital and rifampin. They require UDP-glucuronic acid as a donor, which is produced from UDP-glucose by UDP-glucose dehydrogenase. Thus, UGT activity integrates nutrient-derived cofactors with gene regulation to influence detoxification capacity across tissues.