UGTs

UGTs, or UDP-glucuronosyltransferases, are a family of enzymes that catalyze glucuronidation, a major phase II detoxification reaction. They transfer the glucuronic acid moiety from UDP-glucuronic acid to a wide range of substrates, including drugs, environmental chemicals, bilirubin, and hormones, increasing their water solubility and promoting renal or biliary excretion.

In humans, UGTs are encoded by several gene families, most notably UGT1 and UGT2. The UGT1 family produces multiple isoforms through alternative promoter usage and splicing, while the UGT2 family includes UGT2B and related genes. Expression is highest in the liver and intestine, with tissue-specific patterns that influence substrate handling. UGTs operate alongside other detoxification pathways to limit the bioactivity and persistence of many endogenous and exogenous compounds.

Genetic variation in UGT genes affects drug metabolism and disease risk. For example, variants in UGT1A1 can reduce enzyme expression and activity, contributing to Gilbert syndrome and altered bilirubin clearance. UGT2B7 metabolizes several opioids and other drugs, influencing analgesic response. UGT activity can be induced or inhibited by various medications and dietary factors, altering the clearance of concomitant drugs and risk of adverse effects.

In plants, a related group known as UDP-glucosyltransferases (also abbreviated UGTs) uses UDP-glucose to transfer sugar moieties to small molecules. Plant UGTs participate in the biosynthesis and modification of flavonoids, hormones, and other secondary metabolites, affecting solubility, stability, and bioactivity.

Overall, UGTs are essential for detoxification and clearance of endogenous and exogenous compounds, with significant implications for pharmacokinetics, pharmacogenomics, and metabolic regulation.