UGT1A1entsyymien

UGT1A1 enzymes refer to the hepatic UDP-glucuronosyltransferase 1A1, a member of the UGT1A enzyme family. These enzymes catalyze glucuronidation, a phase II metabolism reaction that attaches glucuronic acid to bilirubin, steroids, estrogens, and many drugs, increasing their solubility and enabling excretion in bile or urine. UGT1A1 is primarily expressed in the liver, with additional expression in other tissues.

The UGT1A1 gene is located on chromosome 2q37 within the UGT1A gene cluster. The gene architecture uses a common set of downstream exons (2–5) encoding the catalytic domain, combined with distinct first exons (such as exon 1A1) that confer substrate specificity to generate different UGT1A isoforms.

Clinical relevance includes Gilbert syndrome, a benign condition caused by reduced UGT1A1 expression due to promoter polymorphisms, notably a TA repeat in the TATA-like region (A(TA)7TAA). This leads to mild unconjugated hyperbilirubinemia, particularly during illness or stress. More severe reductions in UGT1A1 activity underlie Crigler-Najjar syndromes.

In pharmacogenomics, UGT1A1 activity influences the metabolism and toxicity of certain drugs. A well-studied example is irinotecan, where impaired glucuronidation of its active metabolite SN-38 increases risk of neutropenia and diarrhea. Genetic testing for UGT1A1 variants can inform dose adjustments in chemotherapy and other medications. Ongoing research aims to expand the catalogue of UGT1A1 substrates and to clarify how genetic variation affects drug response and bilirubin handling.