UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4gene.
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5′ exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although it is more active on amines, steroids, and sapogenins. It is the main enzyme responsible for glucuronidation of the anticonvulsantlamotrigine.
Bosma PJ, Chowdhury JR, Huang TJ, et al. (1992). "Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I.". FASEB J.6 (10): 2859–63. PMID1634050.
Ritter JK, Crawford JM, Owens IS (1991). "Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells.". J. Biol. Chem.266 (2): 1043–7. PMID1898728.
Moghrabi N, Clarke DJ, Boxer M, Burchell B (1994). "Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2.". Genomics18 (1): 171–3. doi:10.1006/geno.1993.1451. PMID8276413.
Aono S, Yamada Y, Keino H, et al. (1994). "Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II.". Biochem. Biophys. Res. Commun.197 (3): 1239–44. doi:10.1006/bbrc.1993.2610. PMID8280139.
van Es HH, Bout A, Liu J, et al. (1993). "Assignment of the human UDP glucuronosyltransferase gene (UGT1A1) to chromosome region 2q37.". Cytogenet. Cell Genet.63 (2): 114–6. doi:10.1159/000133513. PMID8467709.
Strassburg CP, Oldhafer K, Manns MP, Tukey RH (1997). "Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue.". Mol. Pharmacol.52 (2): 212–20. PMID9271343.
Strassburg CP, Manns MP, Tukey RH (1998). "Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8.". J. Biol. Chem.273 (15): 8719–26. doi:10.1074/jbc.273.15.8719. PMID9535849.
Hiller A, Nguyen N, Strassburg CP, et al. (1999). "Retigabine N-glucuronidation and its potential role in enterohepatic circulation.". Drug Metab. Dispos.27 (5): 605–12. PMID10220490.
Nakajima M, Tanaka E, Kwon JT, Yokoi T (2003). "Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes.". Drug Metab. Dispos.30 (12): 1484–90. doi:10.1124/dmd.30.12.1484. PMID12433823.
Zhang JY, Zhan J, Cook CS, et al. (2003). "Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism.". Drug Metab. Dispos.31 (5): 652–8. doi:10.1124/dmd.31.5.652. PMID12695355.
Kuehl GE, Murphy SE (2004). "N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases.". Drug Metab. Dispos.31 (11): 1361–8. doi:10.1124/dmd.31.11.1361. PMID14570768.