UDP-glucuronosyltransferase 1-9 and UDP-glucuronosyltransferase 1-1 (UGT1A9 and UGT1A1)

UDP-glucuronosyltransferase 1-9 (UGT1A9) and UDP-glucuronosyltransferase 1-1 (UGT1A1) are essential Phase II drug-metabolizing enzymes belonging to the UGT1A subfamily (Source: UniProt P22309, Q9HAW9). These enzymes are primarily located in the endoplasmic reticulum of hepatocytes and enterocytes, where they catalyze the conjugation of glucuronic acid to various endogenous compounds and xenobiotics, significantly increasing their water solubility for excretion (Source: PharmGKB). UGT1A1 is the sole enzyme responsible for the glucuronidation of bilirubin; genetic deficiencies in this enzyme lead to hyperbilirubinemia conditions such as Gilbert syndrome and Crigler-Najjar syndrome (Source: NIH StatPearls). Beyond endogenous metabolism, UGT1A1 is critical for the detoxification of SN-38, the active and toxic metabolite of the anticancer drug irinotecan (Source: FDA Irinotecan Label). UGT1A9 has a broad substrate specificity, metabolizing a wide range of drugs including mycophenolic acid, propofol, and various kinase inhibitors like sorafenib (Source: PubMed PMID: 15536605). Genetic polymorphisms in both UGT1A1 and UGT1A9 are major determinants of inter-individual variability in drug response and the risk of adverse drug reactions, making them key targets for pharmacogenetic screening in clinical oncology and transplant medicine (Source: CPIC Guidelines).

Other names

UGT1A9UGT1A1UDP-glucuronosyltransferase 1A9UDP-glucuronosyltransferase 1A1UDPGT 1-9UDPGT 1-1Bilirubin-UGT1UGT1*1UGT1*9GNT1HUG-BR1

Drugs interact with these enzymes primarily as substrates for glucuronidation, leading to detoxification and excretion, or as inhibitors/inducers that alter the metabolic clearance of co-administered medications (Source: UniProt P22309, Q9HAW9).