UDP-glucuronosyltransferase 1-1 (UGT1A1) (UGT1A1)

UDP-glucuronosyltransferase 1-1 (UGT1A1) is a vital Phase II biotransformation enzyme primarily located in the endoplasmic reticulum of hepatocytes (UniProt: P22309). Its primary biological function is the glucuronidation of various endogenous and exogenous compounds, most notably bilirubin and therapeutic drugs like the HIV integrase inhibitor raltegravir (PubMed: 18072831). By attaching a glucuronic acid moiety to these lipophilic substances, UGT1A1 increases their water solubility, thereby facilitating their elimination via bile or urine. Genetic polymorphisms in the UGT1A1 gene, such as the UGT1A1*28 allele, result in reduced enzyme expression and are associated with Gilbert syndrome and an increased risk of toxicity from drugs like irinotecan and raltegravir (NIH: Genetic Testing Registry). In clinical practice, UGT1A1 is a major determinant of the pharmacokinetic profile of raltegravir, as the drug is eliminated almost exclusively through this pathway without significant involvement of the cytochrome P450 system (FDA: Isentress Label). Consequently, inhibitors of UGT1A1, such as atazanavir, can significantly increase raltegravir plasma concentrations, necessitating careful monitoring for adverse effects.

Other names

UGT1UGT1AUDPGT 1-1Bilirubin-specific UDPGTGNT1UDP-glucuronosyltransferase 1A1

UGT1A1 catalyzes the transfer of a glucuronic acid moiety from UDP-glucuronic acid to a substrate molecule, such as raltegravir, to form a water-soluble glucuronide conjugate for excretion.