UDP-glucuronosyltransferase 1A4 (UGT1A4) (UGT1A4)

UDP-glucuronosyltransferase 1A4 (UGT1A4) is a critical Phase II drug-metabolizing enzyme primarily expressed in the human liver and gastrointestinal tract [1, 10]. It belongs to the UGT1A family and is uniquely characterized by its high catalytic activity toward primary, secondary, and tertiary amines, as well as certain steroids and sapogenins [7, 8]. UGT1A4 is the principal enzyme responsible for the glucuronidation of several widely used medications, including the anticonvulsant lamotrigine and antipsychotics like olanzapine and clozapine [6, 8]. Genetic polymorphisms, most notably the UGT1A4*2 and UGT1A4*3 variants, can significantly alter enzyme activity, leading to substantial interindividual differences in drug clearance and clinical response [6, 7]. In the context of oncology, UGT1A4-mediated deactivation of drugs has been identified as a mechanism of resistance, prompting research into selective inhibitors to restore drug sensitivity [2]. Understanding UGT1A4 function is essential for predicting drug-drug interactions and optimizing personalized dosing regimens in psychiatry and neurology [8, 11].

Other names

UDP-glucuronosyltransferase 1-4UDP-glucuronosyltransferase 1-DHUG-BR2GNT1UDPGT 1-4UGT1DUDP-glucuronosyltransferase 1A4SBilirubin-specific UDPGT isozyme 2

Drugs targeting UGT1A4 primarily act through enzyme inhibition to overcome drug resistance or enzyme induction (via nuclear receptors like PXR and GR) to modulate metabolic clearance; most interacting drugs serve as substrates for N-glucuronidation [2, 4, 11].