PharmGKB summary

Abstract

The uridine diphosphate glucuronosyltransferase (UGT) enzymes are a superfamily of enzymes responsible for the glucuronidation of target substrates. The transfer of glucuronic acid renders xenobiotics and other endogenous compounds water soluble, allowing for their biliary or renal elimination [1]. The UGT family is responsible for the glucuronidation of hundreds of compounds, including hormones, flavonoids, and environmental mutagens [1]. Most of the members of the UGT family are expressed in the liver, as well as in other types of tissues, such as intestinal, stomach, or breast tissues. A few members are expressed only extrahepatically, such as UGT1A7, UGT1A8, UGT1A10, and UGT2A1 [2]. Four families exist within the UGT superfamily: UGT1A, UGT2, UGT3, and UGT8 [3]. UGT2 is further divided into two subfamilies, UGT2A and UGT2B, both of which are present on chromosome 4 [2]. UGT2A enzymes are involved in the glucuronidation of compounds such as phenolic odorants and polycyclic aromatic hydrocarbon metabolites, although limited studies have been carried out on this subfamily [4]; UGT2B proteins are mainly responsible for the metabolism of steroids [5]. The roles of UGT3 and UGT8 family members have not been well characterized [3]. The UGT1A family is located on chromosome 2q37, and the members of this group glucuronidate a large variety of compounds. Pharmaceutical drugs are a common substrate of the UGT1A family [1], making the enzymes in this group relevant to pharmacogenetic research. This very important pharmacogene summary on UGT1A1 is available with interactive links to genetic variants and drugs on the PharmGKB website at http://www.pharmgkb.org/gene/PA420.