UGT1A6

UGT1A6, short for UDP-glucuronosyltransferase 1A6, is an enzyme in the UDP-glucuronosyltransferase (UGT) superfamily. It is encoded by the UGT1A6 gene, which is part of the UGT1A gene cluster on chromosome 2q37. The enzyme resides in the endoplasmic reticulum of hepatocytes and other tissues and mediates the transfer of glucuronic acid from UDP-glucuronic acid to small lipophilic substrates, producing glucuronides that are more water-soluble and more readily excreted in urine or bile.

UGT1A6 has a relatively broad substrate range among phenolic compounds. It glucuronidates substances such as acetaminophen (paracetamol), serotonin, 4-nitrophenol, and other phenols and catechols. The enzyme contributes to phase II detoxification in the liver and in extrahepatic tissues, including the intestine, kidney, and brain, aiding in the elimination of potentially harmful compounds. Its activity can be influenced by physiological factors such as age and disease, as well as by interactions with other drugs.

Genetic variations in UGT1A6 exist in the population and can alter enzymatic activity. Polymorphisms can modify the rate of glucuronidation for UGT1A6 substrates, contributing to interindividual differences in drug exposure and response. This has implications for pharmacokinetics and adverse effect risk for medications that rely on UGT1A6-mediated metabolism. Drug–drug interactions, environmental factors, and other genetic variants can further influence UGT1A6 function.