UGT1A1 Human

The UGT1A1 gene is located on chromosome 2 in humans . It is part of a complex locus that includes thirteen unique alternative first exons followed by four common exons . Four of these alternative first exons are considered pseudogenes . The remaining nine 5’ exons can be spliced to the four common exons, resulting in nine different proteins with distinct N-termini but identical C-termini . Each first exon encodes the substrate binding site and is regulated by its own promoter .

UGT1A1 is involved in the glucuronidation process, where it catalyzes the transfer of glucuronic acid from uridine diphosphate glucuronic acid (UDPGA) to various substrates . This process transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites . This transformation is crucial for the detoxification and elimination of these compounds from the body .

Over 100 genetic variants within the UGT1A1 gene have been identified, some of which result in increased, reduced, or inactive enzymatic activity . These variants can have significant clinical implications. For example, mutations in the UGT1A1 gene can lead to disorders in bilirubin metabolism, such as Gilbert syndrome and Crigler-Najjar syndrome . Gilbert syndrome is often associated with the UGT1A1*28 allele, which impairs proper transcription of the UGT1A1 gene, leading to reduced enzyme activity and hyperbilirubinemia .

Recombinant UGT1A1 is a human-made version of the enzyme produced through recombinant DNA technology. This technology allows for the production of large quantities of the enzyme for research and therapeutic purposes. Recombinant UGT1A1 is used in various studies to understand the enzyme’s function, its role in drug metabolism, and its involvement in genetic disorders.