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UGT2B4  -  UDP glucuronosyltransferase 2 family,...

Homo sapiens

Synonyms: HLUG25, Hyodeoxycholic acid-specific UDPGT, UDP-glucuronosyltransferase 2B4, UDPGT 2B4, UDPGT2B4, ...
 
 
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Disease relevance of UGT2B4

 

High impact information on UGT2B4

 

Chemical compound and disease context of UGT2B4

 

Biological context of UGT2B4

 

Anatomical context of UGT2B4

 

Associations of UGT2B4 with chemical compounds

  • UGT2B4 demonstrates reactivity toward 5alpha-reduced androgens and catechol estrogens, but at a significantly lower level than UGT2B7, 2B15, and 2B17 [16].
  • These variations in the UGT2B4 sequence lead to an amino acid change from aspartic acid to glutamic acid at position 458 [8].
  • Treatment of stable cells with actinomycin D reveals that UGT2B transcripts are stable for 12 h, except for the UGT2B4 transcript, which was decreased by 50% after the 12-h incubation period [16].
  • Screening for RNA expression by RT-PCR confirmed the absence of UGT2B4 and UGT1A6 and showed expression of UGT2B7, a hepatic isoform shown to glucuronidate androsterone, in all intestinal segments [17].
  • In the previous UGT2B11 cDNA (which has subsequently been renamed UGT2B4 (L109,396, D458)), leucine residues are found at positions 109 and 396, whereas phenylalanines are present at these positions in the UGT2B4(D458) and UGT2B4(E458) enzymes [8].
 

Enzymatic interactions of UGT2B4

 

Other interactions of UGT2B4

  • Significantly lower expression of UGT1A9 and UGT2B4 mRNA was identified in paediatric liver [19].
  • These data permitted a provisional ordering of the genes as UGT2B9-UGT2B4-UGT2B15 [9].
  • A consistent downward trend, reaching statistical significance for UGT1A4, UGT2B4, and UGT2B7, was observed in samples from patients with high inflammation scores [20].
  • In this study, we identify UGT2B4 as an FXR target gene [2].
  • Two human liver UDP-glucuronosyltransferase cDNA clones (HLUGP1 and HLUG25) were individually inserted into the eukaryotic expression vector pKCRH2 [15].
 

Analytical, diagnostic and therapeutic context of UGT2B4

  • The presence of UGT2B4 and 2B7 proteins (52 and 56kDa, respectively) was demonstrated by Western blotting [12].
  • Expression of a human liver cDNA encoding a UDP-glucuronosyltransferase catalysing the glucuronidation of hyodeoxycholic acid in cell culture [21].
  • To investigate this possibility directly, UDPGT was extracted from human liver and kidney tissue and its activity was characterized using MPA as a substrate in vitro, assessing the conversion of MPA to MPAG using analysis by high-performance liquid chromatography [22].
  • The enzyme hyodeoxycholic-acid: UDP-glucuronosyltransferase was purified about 230-fold from a solubilized human liver microsomal preparation utilizing anion-exchange chromatography, ampholyte-displacement chromatography and UDP-hexanolamine--Sepharose affinity chromatography [23].
  • With further UDPGT purification (approximately 200-fold) from kidney extracts using a combination of ammonium sulfate precipitation, followed by anion exchange, hydroxyapatite, and size exclusion chromatography, the enzyme was more than 80% pure when assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [22].

References

  1. Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. Barbier, O., Duran-Sandoval, D., Pineda-Torra, I., Kosykh, V., Fruchart, J.C., Staels, B. J. Biol. Chem. (2003) [Pubmed]
  2. FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity. Barbier, O., Torra, I.P., Sirvent, A., Claudel, T., Blanquart, C., Duran-Sandoval, D., Kuipers, F., Kosykh, V., Fruchart, J.C., Staels, B. Gastroenterology (2003) [Pubmed]
  3. Glucuronidation of hyodeoxycholic acid in human liver. Evidence for a selective role of UDP-glucuronosyltransferase 2B4. Pillot, T., Ouzzine, M., Fournel-Gigleux, S., Lafaurie, C., Radominska, A., Burchell, B., Siest, G., Magdalou, J. J. Biol. Chem. (1993) [Pubmed]
  4. Immunochemical analysis of uridine diphosphate-glucuronosyltransferase in four patients with the Crigler-Najjar syndrome type I. van Es, H.H., Goldhoorn, B.G., Paul-Abrahamse, M., Elferink, R.P., Jansen, P.L. J. Clin. Invest. (1990) [Pubmed]
  5. Role of hydrophilic bile acids and of sterols on cholelithiasis in the hamster. Singhal, A.K., Cohen, B.I., Finver-Sadowsky, J., McSherry, C.K., Mosbach, E.H. J. Lipid Res. (1984) [Pubmed]
  6. Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1. Li, Q., Murphree, S.S., Willer, S.S., Bolli, R., French, B.A. Hum. Gene Ther. (1998) [Pubmed]
  7. Hyodeoxycholic acid: a new approach to gallstone prevention. McSherry, C.K., Mosbach, E.H., Cohen, B.I., Une, M., Stenger, R.J., Singhal, A.K. Am. J. Surg. (1985) [Pubmed]
  8. Characterization and substrate specificity of UGT2B4 (E458): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Lévesque, E., Beaulieu, M., Hum, D.W., Bélanger, A. Pharmacogenetics (1999) [Pubmed]
  9. Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13. Monaghan, G., Clarke, D.J., Povey, S., See, C.G., Boxer, M., Burchell, B. Genomics (1994) [Pubmed]
  10. Prominent but reverse stereoselectivity in propranolol glucuronidation by human UDP-glucuronosyltransferases 1A9 and 1A10. Sten, T., Qvisen, S., Uutela, P., Luukkanen, L., Kostiainen, R., Finel, M. Drug Metab. Dispos. (2006) [Pubmed]
  11. Single nucleotide polymorphisms and haplotype frequencies of UGT2B4 and UGT2B7 in a Japanese population. Saeki, M., Saito, Y., Jinno, H., Tanaka-Kagawa, T., Ohno, A., Ozawa, S., Ueno, K., Kamakura, S., Kamatani, N., Komamura, K., Kitakaze, M., Sawada, J. Drug Metab. Dispos. (2004) [Pubmed]
  12. UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term. Collier, A.C., Ganley, N.A., Tingle, M.D., Blumenstein, M., Marvin, K.W., Paxton, J.W., Mitchell, M.D., Keelan, J.A. Biochem. Pharmacol. (2002) [Pubmed]
  13. UDPGT cDNA expression and UDPGT1 in human liver. Sheen, Y.Y., Owens, I.S., Kim, S.S., Kim, J.E. The Journal of toxicological sciences. (1998) [Pubmed]
  14. Reduction and glucuronidation of naftazone by human and rat liver microsomes. Herber, R., Hercelin, B., Van Cantfort, J., De Graeve, J., Fournel-Gigleux, S., Taguchi, T., Magdalou, J. Drug Metab. Dispos. (1995) [Pubmed]
  15. Stable expression of two human UDP-glucuronosyltransferase cDNAs in V79 cell cultures. Fournel-Gigleux, S., Sutherland, L., Sabolovic, N., Burchell, B., Siest, G. Mol. Pharmacol. (1991) [Pubmed]
  16. Relative enzymatic activity, protein stability, and tissue distribution of human steroid-metabolizing UGT2B subfamily members. Turgeon, D., Carrier, J.S., Lévesque, E., Hum, D.W., Bélanger, A. Endocrinology (2001) [Pubmed]
  17. UDP-glucuronosyltransferases in human intestinal mucosa. Radominska-Pandya, A., Little, J.M., Pandya, J.T., Tephly, T.R., King, C.D., Barone, G.W., Raufman, J.P. Biochim. Biophys. Acta (1998) [Pubmed]
  18. Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7. Mackenzie, P., Little, J.M., Radominska-Pandya, A. Biochem. Pharmacol. (2003) [Pubmed]
  19. Developmental aspects of human hepatic drug glucuronidation in young children and adults. Strassburg, C.P., Strassburg, A., Kneip, S., Barut, A., Tukey, R.H., Rodeck, B., Manns, M.P. Gut (2002) [Pubmed]
  20. UDP glucuronosyltransferase mRNA levels in human liver disease. Congiu, M., Mashford, M.L., Slavin, J.L., Desmond, P.V. Drug Metab. Dispos. (2002) [Pubmed]
  21. Expression of a human liver cDNA encoding a UDP-glucuronosyltransferase catalysing the glucuronidation of hyodeoxycholic acid in cell culture. Fournel-Gigleux, S., Jackson, M.R., Wooster, R., Burchell, B. FEBS Lett. (1989) [Pubmed]
  22. Evidence that tacrolimus augments the bioavailability of mycophenolate mofetil through the inhibition of mycophenolic acid glucuronidation. Zucker, K., Tsaroucha, A., Olson, L., Esquenazi, V., Tzakis, A., Miller, J. Therapeutic drug monitoring. (1999) [Pubmed]
  23. Isolation and characterization of hyodeoxycholic-acid: UDP-glucuronosyltransferase from human liver. Matern, H., Lappas, N., Matern, S. Eur. J. Biochem. (1991) [Pubmed]
 
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