The Human UDP-Glucuronosyltransferases: Structural Aspects and Drug Glucuronidation

Drug Metabolism Reviews

Volumn 35, Issue 4, 2003, Pages 287-303

  Ouzzine, Mohamed ^a   Barré, Lydia ^a   Netter, Patrick ^a   Magdalou, Jacques ^a   Fournel Gigleux, Sylvie ^a  

^a Biopôle de l Université de Lorraine   (France)

Author keywords

[No Author keywords available]

Indexed keywords

17 EPIESTRIOL; 2,3 BUTANEDIONE; 4 HYDROXYBIPHENYL; 4 HYDROXYESTRONE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; ANDROSTERONE; ARGININE; ASPARTIC ACID; BILIRUBIN; CYANAMIDE; DIETHYL PYROCARBONATE; EPITESTOSTERONE; ESTRADIOL; ESTRIOL; ESTRONE DERIVATIVE; ETHINYLESTRADIOL; EUGENOL; GLUCURONIDE; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A6; GLUTAMIC ACID; HISTIDINE; HYODEOXYCHOLIC ACID; IRINOTECAN; RECOMBINANT ENZYME; RECOMBINANT GLUCURONOSYLTRANSFERASE 2B4; RECOMBINANT GLUCURONOSYLTRANSFERASE 2B7; TESTOSTERONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZIDOVUDINE;

CONFERENCE PAPER; DETOXIFICATION; DRUG COMPETITION; DRUG CROSS REACTIVITY; DRUG GLUCURONIDATION; DRUG METABOLISM; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME MECHANISM; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE; GLUCURONIDATION; HUMAN; MOLECULAR RECOGNITION; PROTEIN MOTIF; RISK ASSESSMENT; STRUCTURE ACTIVITY RELATION;

ANIMALS; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HUMANS; PHARMACEUTICAL PREPARATIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0347623265     PISSN: 03602532     EISSN: None     Source Type: Journal    
DOI: 10.1081/DMR-120026397     Document Type: Conference Paper

References (58)

1. Antonio, L., Grillasca, J. P., Taskinen, J., Elovaara, E., Burchell, B., Piet, M. H., Ethell, B., Ouzzine, M., Fournel-Gigleux, S., Magdalou, J. (2002). Characterization of catechol glucuronidation in rat liver. Drug Metab. Dispos. 30:199-207.
2. Bailey, M. J., Dickinson, R. G. (2003). Acyl glucuronide reactivity in perspective: biological consequences. Chem. Biol. Interact. 145:117-137.
3. Bhasker, C. R., McKinnon, W., Stone, A., Lo, A. C., Kubota, T., Ishizaki, T., Miners, J. O. (2000). Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance. Pharmacogenetics 10:679-685.
4. Battaglia, E., Pritchard, M., Ouzzine, M., Fournel-Gigleux, S., Radominska, A., Siest, G., Magdalou, J. (1994a). Chemical modification of human UDP-glucuronosyltransferase UGT1*6 by diethylpyrocarbonate: possible involvement of a histidine residue in the catalytic process. Arch. Biochem. Biophys. 309:266-272.
5. Battaglia, E., Senay, C., Fournel-Gigleux, S., Herber, R., Siest, G., Magdalou, J. (1994b). The chemical modification of human liver UDP-glucuronosyltransferase UGT1*6 reveals the involvement of a carboxyl group in catalysis. FEBS Lett. 346:146-150.
6. Bossuyt, X., Blanckaert, N. (2001). Differential regulation of UDP-GlcUA transport in endoplasmic reticulum and in golgi membranes. J. Hepatol. 34:210-214.
7. Campbell, J. A., Davies, G. J., Bulone, V., Henrissat, B. (1997). A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326:929-939.
8. Ciotti, M., Marrone, A., Potter, C., Owens, I. S. (1997). Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics 7:485-495.
9. Ciotti, M., Cho, J. W., George, J., Owens, I. S. (1998). Required buried alphahelical structure in the bilirubin UDP-glucuronosyltransferase, UGT1A1, contains a nonreplaceable phenylalanine. Biochemistry 37:11018-11025.
10. Coffman, B. L., Kearney, W. R., Green, M. D., Lowery, R. G., Tephly, T. R. (2001). Analysis of opioid binding to UDP-glucuronosyltransferase UGT2B7 fusion proteins using nuclear magnetic resonance spectroscopy. Mol. Pharmacol. 59:1464-1469.
11. Coffman, B. L., Kearney, W. R., Goldsmith, S., Knosp, B. M., Tephly, T. R. (2003). Opioids bind to the aminoacid 84 to 118 of UDP-glucuronosyltransferase UGT2B7. Mol. Pharmacol. 63:283-288.
12. Court, M. H., Duan, S. X., Guillemette, C., Journault, K., Krishnaswamy, S., Von Moltke, L. L., Greenblatt, D. J. (2002). Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9. Drug Metab. Dispos. 30:1257-1265.
13. Dubois, S. G., Beaulieu, M., Levesque, E., Hum, D. W., Belanger, A. (1999). Alteration of human UDP-glucuronosyltransferase UGT2B17 regio-specificity by a single amino acid substitution. J. Mol. Biol. 289:29-39.
14. Duvaldestin, P., Mahu, J. L., Preaux, A. M., Berthelot, P. (1976). Novobiocin-inhibition and magnesium-inetraction of rat liver microsomal bilirubin UDP-glucuronosyltransferase. Biochem. Pharmacol. 25:2587-2592.
15. Fournel-Gigleux, S., Sutherland, L., Sabolovic, N., Burchell, B., Siest, G. (1991). Stable expression of two human UDP-glucuronosyltransferase cDNAs in V79 cell cultures. Mol. Pharmacol. 39:177-183.
16. Ghosh, S. S., Sappal, B. S., Kalpana, G. V., Lee, S. W., Chowdhury, J. R., Chowdhury, N. R. (2001). Homodimerization of human bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) and its functional implications. J. Biol. Chem. 276:42108-42115.
17. Grancharov, K., Naydenova, Z., Lozeva, S., Golovinsky, E. (2001). Natural and synthetic inhibitors of UDP-glucuronosyltransferase. Pharm. Ther. 89:171-186.
18. Gschaidmeier, H., Bock, K. W. (1994). Radiation inactivation analysis of microsomal UDP-glucuronosyltransferases catalyzing mono- and diglucuronide formation of 3,6-dihydroxybenzo(a)pyrene and 3,6-dihydroxychrysene. Biochem. Pharmacol. 48:1545-1549.
19. Guengerich, F. P., Parikh, A., Johnson, E. F., Richardson, T. H., von Wachenfeldt, C., Cosme, J., Jung, F., Strassburg, C. P., Manns, M. P., Tukey, R. H., Pritchard, M., Fournel-Gigleux, S., Burchell, B. (1997). Heterologous expression of human drug-metabolizing enzymes. Drug Metab. Dispos. 25:1234-1241.
20. Guillemette, C., Villeneuve, L. (2003). Substrate-dependant impact of a novel exon 1 polymorphism in the human UGT1A9 gene. Drug Metab. Rev. 35(suppl 1):59.
21. Guillemette, C., Ritter, J. K., Auyeung, D. J., Kessler, F. K., Housman, D. E. (2000). Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGTIA7 gene. Pharmacogenetics 10:629-644.
22. Herber, R., Hercelin, B., van Cantford, J., De Graeve, J., Fournel-Gigleux, S., Tagushi, T., Magdalou, J. (1995). Reduction and glucuronidation of naftazone by human and rat liver microsomes. Drug Metab. Dispos. 23:1305-1314.
23. Huang, Y. H., Galijatovic, A., Nguyen, N., Geske, D., Beaton, D., Green, J., Green, M., Peters, W. H., Tukey, R. H. (2002). Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3. Pharmacogenetics 12:287-297.
24. Ikushiro, S., Emi, Y., Iyanagi, T. (1997). Protein-protein interactions between UDP-glucuronosyltransferase isozymes in rat hepatic microsomes. Biochemistry 36:7154-7161.
25. Ikushiro, S., Emi, Y., Kimura, S., Iyanagi, T. (1999). Chemical modification of rat hepatic microsomes with N-ethylmaleimide results in inactivation of both UDP-N-acetylglucosamine-dependent stimulation of glucuronidation and UDP-GlcUA uptake. Biochim. Biophys. Acta 1428:388-396.
26. Ikushiro, S., Emi, Y., Iyanagi, T. (2002). Activation of glucuronidation through a disulfide bond in rat UDP-glucuronosyltransferase 1A6. Biochemistry 41:12813-12820.
27. Ikushiro, S., Murakami, Y., Emi, Y., Iyanagi, T. (2003). Hetero-oligomeric interaction between UDP-glucuronosyltransferase (UGT) isozymes and hepatic microsomes. Drug Metab. Rev. 35(suppl 1):58.
28. Ishii, Y., Miyoshi, A., Watanabe, R., Tsuruda, K., Tsuda, M., Yamaguchi-Nagamatsu, Y., Yoshisue, K., Tanaka, M., Maji, D., Ohgiya, S., Oguri, K. (2001). Simultaneous expression of guinea pig UDP-glucuronosyltransferase 2B21 and 2B22 in COS-7 cells enhances UDP-glucuronosyltransferase 2B21-catalyzed morphine-6-glucuronide formation. Mol. Pharmacol. 60:1040-1048.
29. Iwano, H., Yokota, H., Ohgiya, S., Yuasa, A. (1999). The significance of amino acid residue Asp-446 for enzymatic stability of rat UDP-glucuronosyltransferase UGT1A6. Arch. Biochem. Biophys. 363:116-120.
30. Jackson, M. R., Fournel-Gigleux, S., Harding, D., Burchell, B. (1998). Examination of the substrate specificity of cloned rat kidney phenol UDP-glucuronosyltransferase expressed in COS-7 cells. Mol. Pharm. 34:638-642.
31. Jin, C. J., Miners, J. O., Lillywhite, K. J., Mackenzie, P. I. (1993). cDNA cloning and expression of two new members of the human liver UDP-glucuronosyltransferase 2B subfamily. Biochem. Biophys. Res. Commun. 194:496-503.
32. King, C. D., Rios, G. R., Assouline, J. A., Tephly, T. R. (1999). Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate. Arch. Biochem. Biophys. 365:156-162.
33. Koiwai, O., Aono, S., Adachi, Y., Kamisako, T., Yasuil, Y., Nishizawa, M., Sato, H. (1996). Crigler-Najjar syndrome type II is inherited both as a dominant and as a recessive trait. Hum. Mol. Genet. 5:645-647.
34. Kurkela, M., Garcia-Horsman, A., Luukkanen, L. Mörsky, S., Taskinen, J., Baumann, M., Kostiainen, R., Hirvonen, J., Finel, M. (2003). Expression and characterization of recombinant human UDP-glucuronosyltransferases (UGTs); UGT1A9 is more resistant to detergent inhibition than the other UGTs, and was purified as an active dimeric enzyme. J. Biol. Chem. 278:3536-3544.
35. Levesque, E., Beaulieu, M., Hum, D. W., Belanger, A. (1999). Characterization and substrate specificity of UGT2B4 (E458): a UDP-glucuronosyltransferase encoded by a polymorphic gene. Pharmacogenetics. 9:207-216.
36. Mackenzie, P. I. (1990). Expression of chimeric cDNAs in cell culture defines a region of UDP glucuronosyltransferase involved in substrate selection. J. Biol. Chem. 265:3432-3435.
37. Mackenzie, P. I., Owens, I. S., Burchell, B., Bock, K. W., Bairoch, A., Belanger, A., Fournel-Gigleux, S., Green, M., Hum, D. W., Iyanagi, T., Lancet, D., Louisot, P., Magdalou, J., Roy-Chowdhury, J., Ritter, J. K., Schachter, H., Tephly, T. R., Tipton, K. K., Nebert, D. W. (1997). The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics. 7:255-269.
38. Matern, H., Matern, S., Gerok, W. (1982). Isolation and characterization of rat liver microsomal UDP-glucuronosyltransferase activity toward chenodeoxycholic acid and testosterone as a single form of enzyme. J. Biol. Chem. 257:7422-7429.
39. Meech, R., Mackenzie, P. I. (1997). UDP-glucuronosyltransferase, the role of amino acid terminus in dimerization. J. Biol. Chem. 272:26913-26917.
40. Meech, R., Mackenzie, P. I. (1998). Determinants of UDP glucuronosyltransferase membrane association and residency in the endoplasmic reticulum. Arch. Biochem. Biophys. 356:77-85.
41. Meech, R., Yogalingam, G., Mackenzie, P. I. (1996). Mutational analysis of the carboxy-terminal region of UDP-glucuronosyltransferase 2B1. DNA Cell Biol. 15:489-494.
42. Monaghan, G., Ryan, M., Seddon, R., Hume, R., Burchell, B. (1996). Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet 347:578-581.
43. Muraoka, M., Kawakita, M., Ishida, N. (2001). Molecular characterization of human UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter, a novel nucleotide sugar transporter with dual substrate specificity. FEBS Lett. 495:87-93.
44. Ouzzine, M., Magdalou, J., Burchell, B., Fournel-Gigleux, S. (1999a). An internal signal sequence mediates the targeting and retention of the human UDP-glucuronosyltransferase 1A6 to the endoplasmic reticulum. J. Biol. Chem. 274:31401-31409.
45. Ouzzine, M., Magdalou, J., Burchell, B., Fournel-Gigleux, S. (1999b). Expression of a functionally active human hepatic UDP-glucuronosyltransferase (UGT1A6) lacking the N-terminal signal sequence in the endoplasmic reticulum. FEBS Lett. 45:4187-4191.
46. Ouzzine, M., Antonio, L., Burchell, B., Netter, P., Fournel-Gigleux, S., Magdalou, J. (2000). Importance of histidine residues for the function of the human liver UDP-glucuronosyltransferase UGT1A6: evidence for the catalytic role of histidine 370. Mol. Pharmacol. 58:1609-1615.
47. Peters, W. H., Jansen, P. L., Nauta, H. (1984). The molecular weights of UDP-glucuronyltransferase determined with radiation-inactivation analysis. A molecular model of bilirubin UDP-glucuronyltransferase. J. Biol. Chem. 259:11701-11705.
48. Pillot, T., Ouzzine, M., Fournel-Gigleux, S., Lafaurie, C., Tebbi, D., Treat, S., Radominska, A., Lester, R., Siest, G., Magdalou, J. (1993). Determination of the human liver UDP-glucuronosyltransferase 2B4 domains involved in the binding of UDP-glucuronic acid using photoaffinity labeling of fusion proteins. Biochem. Biophys. Res. Commun. 197:785-791.
49. Pritchard, M., Fournel-Gigleux, S., Siest, G., Mackenzie, P., Magdalou, J. (1994). A recombinant phenobarbital-inducible rat liver UDP-glucuronosyltransferase (UDP-glucuronosyltransferase 2B1 stabily expressed in V79 cells catalyzes the glucuronidation of morphine, phenols, and carboxylic acids. Mol. Pharmacol. 45:42-50.
50. Radominska-Pandya, A., Czernik, P. J., Little, J. M., Battaglia, E., Mackenzie, P. I. (1999). Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab. Rev. 31:817-899.
51. Senay, C., Ouzzine, M., Battaglia, E., Pless, D., Cano, V., Burchell, B., Radominska, A., Magdalou, J., Fournel-Gigleux, S. (1997). Arginine 52 and histidine 54 located in a conserved N-terminal hydrophobic region (LX2-R52-G-H54-X3-V-L) are important amino acids for the functional and structural integrity of the human liver UDP-glucuronosyltransferase UGT1*6. Mol. Pharmacol. 51:406-413.
52. Senay, C., Jedlitschky, G., Terrier, N., Burchell, B., Magdalou, J., Fournel-Gigleux, S. (2002). The importance of cysteine 126 in the human liver UDP-glucuronosyltransferase UGT1A6. Biochim. Biophys. Acta 1597:90-96.
53. Shepherd, S. R., Baird, S. J., Hallinan, T., Burchell, B. (1989). An investigation of the transverse topology of bilirubin UDP-glucuronosyltransferase in rat hepatic endoplasmic reticulum. Biochem. J. 259:617-620.
54. Sorich, M. J., Smith, P. A., McKinnon, R. A., Miners, J. O. (2002). Pharmacophore and quantitative structure activity relationship modelling of UDP-glucuronosyltransferase 1A1 (UGT1A1) substrates. Pharmacogenetics 12:635-645.
55. Takenaga, N., Ishii, M., Kamei, T., Yasumori, T. (2002). Structure-activity relationship in O-glucuronidation of indolcarbazole analogs. Drug Metab. Dispos. 30:494-497.
56. Tukey, R. H., Strassburg, C. P. (2000). Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu. Rev. Pharmacol. Toxicol. 40:581-616.
57. Tukey, R. H., Strassburg, C. P., Mackenzie, P. I. (2002). Pharmacogenomics of human UDP-glucuronosyltransferases and irinotecan toxicity. Mol. Pharmacol. 62:446-450.
58. Zenser, T. V., Lakshmi, V. M., Fu Hsu, F., Davis, B. B. (2002). Metabolism of N-acylbenzidine and initiation of bladder cancer. Mutation Res. 506-507:29-40.