UGTentsyymien

UGTentsyymien, or UDP-glucuronosyltransferases (UGTs), are a family of enzymes that catalyze glucuronidation, a major phase II detoxification reaction. In glucuronidation, UDP-glucuronic acid donates a glucuronic moiety to a wide range of substrates, including bilirubin, steroid hormones, and many drugs. The resulting glucuronides are typically more water-soluble and are excreted via bile or urine.

Most UGTs are resident in the endoplasmic reticulum of liver cells and other tissues such as the intestine, kidney, and brain. The human UGT gene family is divided mainly into UGT1A and UGT2B subfamilies, with additional members including UGT2A and others. The UGT1A family is structurally complex: it generates multiple isoforms through alternative splicing of exon 1 in combination with common exons 2–5 (for example UGT1A1, UGT1A4, UGT1A9). UGT2B enzymes, such as UGT2B7, provide broad drug- and endogenous-substrate activity.

Substrates include bilirubin, hormones, bile acids, and a wide range of pharmaceuticals such as acetaminophen, morphine, lorazepam, and nonsteroidal anti-inflammatory drugs. The specificity and activity of individual UGTs influence individual drug clearance and response.

Genetic variation in UGT genes contributes to interindividual differences in metabolism. For example, reduced UGT1A1 activity due to promoter polymorphisms is associated with Gilbert’s syndrome and higher unconjugated bilirubin. UGT activity can be induced or inhibited by various xenobiotics, affecting drug interactions and toxicity risk. Neonates have limited UGT activity, which matures during infancy.