The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification

International Journal of Biochemistry and Cell Biology

Volumn 45, Issue 6, 2013, Pages 1121-1132

  Rowland, Andrew ^a   Miners, John O ^a   Mackenzie, Peter I ^a  

^a FLINDERS UNIVERSITY   (Australia)

Author keywords

Detoxification; Drug metabolism; Elimination; Glucuronidation; UDP glucuronosyltransferase

Indexed keywords

GLUCURONIC ACID; TRANSCRIPTION FACTOR;

CATALYSIS; CELLULAR DISTRIBUTION; DRUG DETOXIFICATION; DRUG METABOLISM; ENZYME POLYMORPHISM; ENZYME REGULATION; GLUCURONIDATION; MOLECULAR INTERACTION; ONTOGENY; REVIEW; TISSUE DISTRIBUTION;

CATALYSIS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GLUCURONIC ACID; GLUCURONOSYLTRANSFERASE; HUMANS; LIVER; METABOLIC DETOXICATION, DRUG; PHARMACOKINETICS;

EID: 84875924213     PISSN: 13572725     EISSN: 18785875     Source Type: Journal    
DOI: 10.1016/j.biocel.2013.02.019     Document Type: Review

References (155)

1. B.J. Anderson, A.D. McKee, and N.H. Holford Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients Clinical Pharmacokinetics 33 1987 313 327
2. U.A. Argikar, and R.P. Remmel Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP- glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10 Drug Metabolism and Disposition 37 2009 229 236
3. U.A. Argikar, and R.P. Remmel Variation in glucuronidation of lamotrigine in human liver microsomes Xenobiotica 39 2009 355 363
4. O. Barbier, D. Duran-Sandoval, I. Pineda-Torra, V. Kosykh, J.C. Fruchart, and B. Staels Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme Journal of Biological Chemistry 278 2003 32852 32860
5. O. Barbier, I.P. Torra, A. Sirvent, T. Claudel, C. Blanquart, and D. Duran-Sandoval FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity Gastroenterology 124 2003 1926 1940
6. O. Barbier, L. Villeneuve, V. Bocher, C. Fontaine, I.P. Torra, and C. Duhem The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene Journal of Biological Chemistry 278 2003 13975 13983
7. O. Bernard, and C. Guillemette The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants Drug Metabolism and Disposition 32 2004 775 778
8. P. Bernard, H. Goudonnet, Y. Artur, B. Desvergne, and W. Wahli Activation of the mouse TATA-less and human TATA-containing UDP-glucuronosyltransferase 1A1 promoters by hepatocyte nuclear factor 1 Molecular Pharmacology 56 1999 526 536
9. R.C. Bhasker, W. McKinnon, A. Stone, A.C.T. Lo, T. Kubota, and T. Ishizaki Genetic polymorphism of UDP-glucuronosyltransferase 2B7 (UGT2B7) at amino acid 268: ethnic diversity of alleles and potential clinical significance Pharmacogenetics 10 2000 679 685
10. I.K. Bjorkman, J. Fastborn, I.K. Schmidt, and C.B. Bernstein Drug-drug interactions in the elderly Annals of Pharmacotherapy 36 2002 1675 1681
11. K.W. Bock, and B.S. Bock-Hennig UDP-glucuronosyltransferases (UGTs): from purification of Ah-receptor-inducible UGT1A6 to coordinate regulation of subsets of CYPs, UGTs, and ABC transporters by nuclear receptors Drug Metabolism Reviews 42 2010 5 12
12. A. Bosio, E. Binczek, M.M. Le Beau, A.A. Fernald, and W. Stoffel The human gene CGT encoding the UDP-galactose ceramide galactosyl transferase (cerebroside synthase): cloning, characterization, and assignment to human chromosome 4, band q26 Genomics 34 1996 69 75
13. P.J. Bosma, J. Seppen, B. Goldhoorn, C. Bakker, R.P. Oude Elferink, and J.R. Chowdhury Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man Journal of Biological Chemistry 269 1994 17960 17964
14. P.J. Bosma, J.R. Chowdhury, C. Bakker, S. Gantla, A. de Boer, and B.A. Oostra The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome New England Journal of Medicine 333 1995 1171 1175
15. X. Bossuyt, and N. Blanckaert Carrier mediated transport of uridine diphospho-glucuronic acid across the endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase activity in rat liver Biochemical Journal 323 1997 645 648
16. K. Bowalgaha, and J.O. Miners The glucuronidation of mycophenolic acid by human liver, kidney and jejunum microsomes British Journal of Clinical Pharmacology 52 2001 605 609
17. K. Bowalgaha, D.J. Elliot, P.I. Mackenzie, K.M. Knights, and J.O. Miners The glucuronidation of (4-3-keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6α- and 21-hydroxyprogesterone are selective substrates for UGT2B7 Drug Metabolism and Disposition 35 2007 363 370
18. M.A. Boyd, P. Srasuebkul, K. Ruxrungtham, P.I. Mackenzie, V. Uchaipichat, and M.J. Stek Relationship between hyperbilirubinaemia and UDP- glucuronosyltransferase 1A1 (UGT1A1) polymorphism in adult HIV-infected Thai patients treated with indinavir Pharmacogenet Genomics 16 2006 321 329
19. N.H. Brockmeyer, I. Tillmann, L. Mertins, B. Barthel, and M. Goos Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients European Journal of Medical Research 2 1997 377 383
20. B. Burchell, and M.W. Coughtrie UDP-glucuronosyltransferases Pharmacology and Therapeutics 43 1989 261 289
21. B. Burchell, C.H. Brierley, and D. Rance Specificity of human UDPGlucuronosyltransferases and xenobiotic glucuronidation Life Sciences 6 1995 1819 1831
22. J.M. Butler, and E.J. Begg Free drug metabolic clearance in elderly people Clinical Pharmacokinetics 47 2008 297 321
23. Y. Caraco, J. Sheller, and A.J.J. Wood Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects Journal of Pharmacology and Experimental Therapeutics 290 1999 413 422
24. X.Y. Chen, L.M. Zhao, and D.F. Zhong A novel metabolic pathway of morphine: formation of morphine glucosides in cancer patients British Journal of Clinical Pharmacology 55 2003 570 578
25. H. Chen, H. Webb, J. Evarts, and R. Ulrich UDP-glucuronosyltransferase catalysed hepatic and extra-hepatic glucuronidation: An important elimination mechanism of GS-1101, a potent and selective inhibitor of the p110δ isoform of phosphoinositide 3-kinase for treatment of patients with hematologic malignancies Drug Metabolism Reviews 43 2011 79
26. J.Y. Chung, J.Y. Cho, K.S. Yu, J.R. Kim, H.R. Jung, and K.S. Lim Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers Clinical Pharmacology and Therapeutics 77 2005 486 494
27. J.Y. Chung, J.Y. Cho, K.S. Yu, J.R. Kim, K.S. Lim, and D.R. Sohn Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects Clinical Pharmacology and Therapeutics 83 2008 595 600
28. T. Coetzee, X. Li, N. Fujita, J. Marcus, K. Suzuki, and U. Francke Molecular cloning, chromosomal mapping, and characterization of the mouse UDP-galactose: Ceramide galactosyltransferase gene Genomics 35 1996 215 222
29. M.H. Court, S.X. Duan, C. Guillemette, K. Journault, S. Krishnaswamy, and L.L. Von Moltke 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 Metabolism and Disposition 30 2002 1257 1265
30. M.H. Court, S. Krishnaswamy, Q. Hao, S.X. Duan, C.J. Patten, and L.L. Von Moltke Evaluation of 3′-azido-3′-deoxythymidine, morphine, and codeine as probe substrates for udp-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism Drug Metabolism and Disposition 31 2003 1125 1133
31. M.H. Court Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases Methods in Enzymology 400 2005 104 116
32. M.H. Court Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system Drug Metabolism Reviews 42 2010 209 224
33. M.H. Court, X. Zhang, X. Ding, K.K. Yee, L.M. Hesse1, and M. Finel Quantitative distribution of mRNAs encoding the 19 human UDP- glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues Xenobiotica 42 2012 266 277
34. S.N. de Wildt, G.L. Kearns, J.S. Leeder, and J.N. van den Anker Glucuronidation in humans: pharmacogenetic and developmental aspects Clinical Pharmacokinetics 36 1999 439 452
35. Y. Duguay, C. Baar, F. Skorpen, and C. Guillemette A novel functional polymorphism in the uridine diphosphate-glucuronosyltransferase 2B7 promoter with significant impact on promoter activity Clinical Pharmacology and Therapeutics 75 2004 223 233
36. U. Ehmer, A. Vogel, J.K. Schutte, B. Krone, M.P. Manns, and C.P. Strassburg Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4 Hepatology 39 2004 970 977
37. J. Fevery, M. Van de Vijver, R. Michiels, and K.P. Heirwegh Comparison in different species of biliary bilirubin-IX alpha conjugates with the activities of hepatic and renal bilirubin-IX alpha-uridine diphosphate glycosyltransferases Biochemical Journal 164 1977 737 746
38. M. Finel, and M. Kurkela The UDP-glucuronosyltransferases as oligomeric enzymes Current Drug Metabolism 9 2008 70 76
39. P. Gaganis, J.O. Miners, J.S. Brennan, A. Thomas, and K.M. Knights Human renal cortical and medullary UDP-glucuronosyltransferases (UGTs): immunohistochemical localization of UGT2B7 and UGT1A enzymes and kinetic characterization of S-naproxen glucuronidation Journal of Pharmacology and Experimental Therapeutics 323 2007 422 430
40. D. Gardner-Stephen, J.M. Heydel, A. Goyal, Y. Lu, W. Xie, and T. Lindblom Human PXR variants and their differential effects on the regulation of human UDP-glucuronosyltransferase gene expression Drug Metabolism and Disposition 32 2004 340 347
41. D.A. Gardner-Stephen, and P.I. Mackenzie Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4alpha Pharmacogenetics and Genomics 17 2007 25 36
42. D.A. Gardner-Stephen, and P.I. Mackenzie Isolation of the UDP-glucuronosyltransferase 1A3 and 1A4 proximal promoters and characterization of their dependence on the transcription factor hepatocyte nuclear factor 1alpha Drug Metabolism and Disposition 35 2007 116 120
43. S.S. Ghosh, B.S. Sappal, G.V. Kalpana, S.W. Lee, J.R. Chowdhury, and N.R. Chowdhury Homodimerization of human bilirubin-uridine-diphosphoglucuronate glucuronosyltransferase-1 (UGT1A1) and its functional applications Journal of Biological Chemistry 276 2001 42108 42115
44. P.A. Gregory, D.A. Gardner-Stephen, R.H. Lewinsky, K.N. Duncliffe, and P.I. Mackenzie Cloning and characterization of the human UDP- glucuronosyltransferase 1A8, 1A9, and 1A10 gene promoters: differential regulation through an interior-like region Journal of Biological Chemistry 278 2003 36107 36114
45. P.A. Gregory, D.A. Gardner-Stephen, A. Rogers, M.Z. Michael, and P.I. Mackenzie The caudal-related homeodomain protein Cdx2 and hepatocyte nuclear factor 1alpha cooperatively regulate the UDP-glucuronosyltransferase 2B7 gene promoter Pharmacogenetics and Genomics 16 2006 527 536
46. P.A. Gregory, A.J. Hansen, and P.I. Mackenzie Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter Pharmacogenetics 10 2000 809 820
47. P.A. Gregory, R.H. Lewinsky, D.A. Gardner-Stephen, and P.I. Mackenzie Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 genes by hepatocyte nuclear factor 1alpha and the caudal-related homeodomain protein 2 Molecular Pharmacology 65 2004 953 963
48. Y. Gu, M.D. Tingle, and W.R. Wilson Glucuronidation of the anticancer prodrug PR-104A: species differences, identification of human UDP-glucuronosyltransferases and implications for therapy Journal of Pharmacology and Experimental Therapeutics 337 2011 692 701
49. C. Guillemette, E. Lévesque, M. Harvey, J. Bellemare, and V. Menard UGT genomic diversity: beyond gene duplication Drug Metabolism Reviews 42 2010 24 44
50. X. He, L.M. Hesse, S. Hazarika, G. Masse, J.S. Harmatz, and D.J. Greenblatt Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion British Journal of Clinical Pharmacology 68 2009 721 730
51. M. Holthe, T.N. Rakva, P. Klepstad, J.R. Idle, S. Kaasa, and H.E. Krokan Sequence variations in the UDPglucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients The Pharmacogenomics Journal 3 2003 17 26
52. D.G. Hu, and P.I. Mackenzie Estrogen receptor {alpha}, Fos-related antigen-2 and c-Jun co-ordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17{beta}-estradiol in MCF-7 cells Molecular Pharmacology 76 2009 1 15
53. D.G. Hu, D. Gardner-Stephen, G. Severi, P.A. Gregory, J. Treloar, and G.G. Giles A novel polymorphism in a forkhead box A1 (FOXA1) binding site of the human UDP glucuronosyltransferase 2B17 gene modulates promoter activity and is associated with altered levels of circulating androstane-3alpha,17beta-diol glucuronide Molecular Pharmacology 78 2010 714 722
54. D.G. Hu, and P.I. Mackenzie Forkhead box protein A1 regulates UDP glucuronosyltransferase 2B15 gene transcription in LNCaP prostate cancer cells Drug Metabolism and Disposition 38 2010 2105 2109
55. S. Ichikawa, H. Sakiyama, G. Suzuki, K.I. Hidari, and Y. Hirabayashi Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis Proceedings of the National Academy of Sciences 93 1996 4638 4643
56. S. Ikushiro, Y. Emi, and T. Iyanagi Protein-protein interactions between UDP-glucuronosyltransferase isozymes in rat hepatic microsomes Biochemistry 36 1997 7154 7161
57. M. Ingelman-Sundberg, S.C. Sim, A. Gomez, and C. Rodriguez-Anton Influence of cytochrome P450 polymorphisms on drug therapies: Pharmacogenetic, pharmacoepigenetic and clinical aspects Pharmacology and Therapeutics 116 2007 496 526
58. Y. Ishii, A.J. Hansen, and P.I. Mackenzie Octamer transcription factor-1 enhances hepatic nuclear factor-1 alpha-mediated activation of the human UDP glucuronosyltransferase 2B7 promoter Molecular Pharmacology 57 2000 940 947
59. Y. Ishii, A. Miyoshi, R. Watanabe, K. Tsuruda, M. Tsuda, and Y.Y. Nagamatsu Simultaneous expression of guinea pig UDPglucuronosyltransferase 2B1 and 2B22 in COS-7 cells enhances UDPglucuronosyltransferase 2B21-catalysed morphine-6-glucuronide formation Molecular Pharmacology 60 2001 1040 1048
60. M. Iwai, Y. Maruo, M. Ito, K. Yamamoto, H. Sato, and Y.J. Takeuchi Six novel UDP glucuronosyltransferase (UGT1A3) polymorphisms with varying activity Journal of Human Genetics 49 2004 123 128
61. T. Izukawa, M. Nakajima, R. Fujiwara, H. Yamanaka, T. Fukami, and M. Takamiya Quantitative analysis of UDP-glucuronosyltransferase (UGT) 1A and UGT2B expression levels in human livers Drug Metabolism and Disposition 37 2009 1759 1768
62. C.J. Jin, P.I. Mackenzie, and J.O. Miners The regio- and stereo-selectivity of C19 and C21 hydroxysteroid glucuronidation by UGT2B7 and UGT2B11 Archives of Biochemistry and Biophysics 341 1997 207 211
63. H. Jinno, M. Saeki, Y. Saito, T. Tanaka-Kagawa, N. Hanioka, and K. Sai Functional characterization of human UDP-glucuronosyltransferase 1A9 Variant, D256N, found in Japanese cancer patients Journal of Pharmacology and Experimental Therapeutics 306 2003 688 693
64. P.D. Josephy, F.P. Guengerich, and J.O. Miners "Phase I" and "Phase II" drug metabolism: terminology that we should phase out Drug Metabolism Reviews 37 2005 575 580
65. J. Kaeding, J. Belanger, P. Caron, M. Verreault, A. Belanger, and O. Barbier Calcitrol (1alpha,25-dihydroxyvitamin D3) inhibits androgen glucuronidation in prostate cancer cells Molecular Cancer Therapeutics 7 2008 380 390
66. J. Kaeding, E. Bouchaert, J. Belanger, P. Caron, S. Chouinard, and M. Verreault Activators of the farnesoid X receptor negatively regulate androgen glucuronidation in human prostate cancer LNCAP cells Biochemical Journal 410 2008 245 253
67. N. Kawade, and S. Onishi The prenatal and postnatal development of UDP-glucuronyltransferase activity towards bilirubin and the effect of premature birth on this activity in the human liver Biochemical Journal 196 1981 257 260
68. T.K. Kiang, M.H. Ensom, and T.K. Chang UDP-glucuronosyltransferases and clinical drug-drug interactions Pharmacology and Therapeutics 106 2005 97 132
69. K.M. Knights, L.K. Winner, D.J. Elliot, K. Bowalgaha, and J.O. Miners Aldosterone glucuronidation by human liver and kidney microsomes and recombinant UDP-glucuronosyltransferases: inhibition by NSAIDs British Journal of Clinical Pharmacology 68 2009 402 412
70. K.M. Knights, K. Bowalgaha, and J.O. Miners Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18β-glucuronidation: a potential drug interaction Drug Metabolism and Disposition 38 2010 1011 1014
71. K.M. Knights, and J.O. Miners Renal UDP-glucuronosyltransferases and the glucuronidation of xenobiotics and endogenous mediators Drug Metabolism Reviews 42 2010 60 70
72. K.M. Knights, A. Rowland, and J.O. Miners Renal drug metabolism in humans: the potential for drug-endobiotic interactions involving cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) British Journal of Clinical Pharmacology 2013 10.1111/bcp.12086 [Epub ahead of print]
73. P. Korprasertthaworn, A. Rowland, B.C. Lewis, P.I. Mackenzie, K. Yoovathaworn, and J.O. Miners Effects of amino acid substitutions at positions 33 and 37 on UDP-glucuronosyltransferase 1A9 (UGT1A9) activity and substrate selectivity Biochemical Pharmacology 84 2012 1511 1521
74. S. Krishnaswamy, Q. Hao, A. Al-Rohaimi, L.M. Hesse, L.L. von Moltke, and D.J. Greenblatt UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S) Journal of Pharmacology and Experimental Therapeutics 313 2005 1331 1339
75. M. Kurkela, J.A. Garcia-Horsman, L. Luukkanen, S. Morsky, J. Taskinen, and M. Baumann Expression and characterization of recombinant human UDP-glucuronosyltransferases (UGTs): UGT1A9 is more resistant to detergent inhibition than other UGTs and was purified as an active dimeric enzyme Journal of Biological Chemistry 278 2003 3536 3544
76. T.O. Lankisch, T.C. Gillman, T.J. Erichsen, U. Ehmer, S. Kalthoff, and N. Freiberg Aryl hydrocarbon receptor-mediated regulation of the human estrogen and bile acid UDP-glucuronosyltransferase 1A3 gene Archives of Toxicology 82 2008 573 582
77. J.E. Leakey, R. Hume, and B. Burchell Development of multiple activities of UDP glucuronosyltransferase in human liver Biochemical Journal 243 1987 859 861
78. B.C. Lewis, P.I. Mackenzie, and J.O. Miners Homodimerization of UDP-glucuronosyltransferase 2B7 (UGT2B7) and identification of a putative dimerization domain by protein homology modelling Biochemical Pharmacology 82 2011 2016 2023
79. Y. Lu, J.M. Heydel, X. Li, S. Bratton, T. Lindblom, and A. Radominska-Pandya Lithocholic acid decreases expression of UGT2B7 in Caco-2 cells: a potential role for a negative farnesoid X receptor response element Drug Metabolism and Disposition 33 2005 937 946
80. P.I. Mackenzie, and I.S. Owens Cleavage of nascent UDP glucuronosyltransferase from rat liver and dog pancreas microsomes Biochemical and Biophysical Research Communications 122 1984 1441 1449
81. P.I. Mackenzie Rat liver UDP glucuronosyltransferase. cDNA expression of a form glucuronidating 3-hydroxyandrogens Journal of Biological Chemistry 261 1986 14112 14117
82. P.I. Mackenzie Rat liver UDP glucuronosyltransferase. Identification of cDNAs encoding to enzymes which glucuronidate testosterone, dihydrotestosterone and betaestradiol Journal of Biological Chemistry 262 1987 9744 9749
83. P.I. Mackenzie, J.O. Miners, and R.A. McKinnon Polymorphisms in UDP glucuronosyltransferase genes: functional consequences and clinical relevance Clinical Chemistry and Laboratory Medicine 38 2000 889 892
84. P.I. Mackenzie, J.M. Little, and A. Radominska-Pandya Glucosidation of hyodeoxycholic acid by UDP-glucuronosyltransferase 2B7 Biochemical Pharmacology 65 2003 417 421
85. P.I. Mackenzie, P.A. Gregory, D.A. Gardner-Stephens, R.H. Lewinsky, B.R. Jorgensen, and T. Nishiyama Regulation of UDP-glucuronosyltransferase genes Current Drug Metabolism 4 2003 249 257
86. P.I. Mackenzie, K.W. Bock, B. Burchell, C. Guillemette, S. Ikushiro, and T. Iyanagi Nomenclature update for the mammalian UDP-glucuronosyltransferase (UGT) gene superfamily Pharmacogenetics and Genomics 75 2005 677 685
87. P.I. Mackenzie, A. Rogers, J. Treloar, B.R. Jorgensen, J.O. Miners, and R. Meech Identification of UDP glycosyltransferase 3A1 as a UDP N-acetylglucosaminyltransferase Journal of Biological Chemistry 283 2008 36205 36210
88. P.I. Mackenzie, D.G. Hu, and D.A. Gardner-Stephen The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors Drug Metabolism Reviews 42 2010 95 105
89. P.I. Mackenzie, D.A. Gardner-Stephens, and J.O. Miners UDP-glucuronosyltransferases Comprehensive Toxicology 4 2010 413 433
90. P.I. Mackenzie, A. Rogers, D.J. Elliot, N. Chau, J.A. Hulin, and J.O. Miners The novel UDP glycosyltransferase 3A2: cloning, catalytic properties, and tissue distribution Molecular Pharmacology 79 2011 472 478
91. H.U. Marschall, B. Egestad, H. Matern, S. Matern, and J. Sjovall N-acetylglucosaminides. A new type of bile acid conjugate in man Journal of Biological Chemistry 264 1989 12989 12993
92. D.C. Mays, K.F. Dixon, A. Balboa, L.J. Pawluk, M.R. Bauer, and S. Nawoot A nonprimate animal model application to zidovudine pharmacokinetics in humans: inhibition of glucuronidation and renal excretion of zidovudine by probenecid in rats Journal of Pharmacology and Experimental Therapeutics 259 1991 1261 1265
93. R. Meech, G. Yogalingam, and P.I. Mackenzie Mutational analysis of carboxy-terminal region of UDP-glucuronosyltransferase 2B1 DNA and Cell Biology 15 1996 489 494
94. R. Meech, and P.I. Mackenzie Structure and function of uridine diphosphate-glucuronosyltransferases Clinical and Experimental Pharmacology and Physiology 24 1997 907 915
95. R. Meech, and P.I. Mackenzie UDP-glucuronosyltransferase, the role of the amino terminus in dimerization Journal of Biological Chemistry 272 1997 26913 26917
96. M.J. Miley, A.K. Zielinska, J.E. Keenan, S.M. Bratton, A. Radominska-Pandya, and RedinboM.R. Crystal structure of the cofactor-binding domain of the human phase II drugmetabolism enzyme UDP-glucuronosyltransferase 2B7 Journal of Molecular Biology 369 2007 498 511
97. J.O. Miners, R. Penhall, R.A. Robson, and D.J. Birkett Comparison of paracetamol metabolism in young adult and elderly males European Journal of Clinical Pharmacology 35 1988 157 160
98. J.O. Miners, and P.I. Mackenzie Drug glucuronidation in humans Pharmacology and Therapeutics 51 1991 347 369
99. J.O. Miners, R.A. McKinnon, and P.I. Mackenzie Genetic polymorphisms of UDP-glucuronosyltransferases and their functional significance Toxicology 181 2002 453 456
100. J.O. Miners, P.A. Smith, M.J. Sorich, R.A. McKinnon, and P.I. Mackenzie Predicting human drug glucuronidation parameters: applications of in vitro and in silico modelling approaches Annual Review of Pharmacology and Toxicology 44 2004 1 25
101. J.O. Miners, K.M. Knights, J.B. Houston, and P.I. Mackenzie In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises Biochemical Pharmacology 71 2006 1531 1539
102. J.O. Miners, P.I. Mackenzie, and K.M. Knights The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential Drug Metabolism Reviews 42 2010 196 208
103. J.O. Miners, T.M. Polasek, P.I. Mackenzie, and K.M. Knights The in vitro characterization of inhibitory drug-drug interactions involving UDP-glucuronosyltransferase K.S. Pang, A.D. Rodrigues, R.M. Peter, Enzyme and transporter based drug-drug interactions; Progress and future challenges 2010 Springer New York 217 236
104. S.J. Miyagi, and A.C. Collier Pediatric development of glucuronidation: the ontogeny of hepatic UGT1A4 Drug Metabolism and Disposition 35 2007 1587 1592
105. S.J. Miyagi, and A.C. Collier The development of UDP- glucuronosyltransferases 1A1 and 1A6 in the pediatric liver Drug Metabolism and Disposition 39 2011 912 919
106. S.J. Miyagi, A.M. Milne, M.W. Coughtrie, and A.C. Collier Neonatal development of hepatic UGT1A9: implications of pediatric pharmacokinetics Drug Metabolism and Disposition 40 2012 1321 1327
107. B. Mojarrabi, and P.I. Mackenzie Characterization of two UDP-glucuronosyltransferases that are predominantly expressed in human colon Biochemical and Biophysical Research Communications 247 1998 704 709
108. Y. Motoyama Studies of human liver bilirubin-glycosyl transferase. Bilirubin UDP-xylosyl and UDP-glucuronyl transferase activities in diseased human livers Enzyme 24 1979 158 162
109. K. Oguri, N. Hanioka, and Yoshimura Species differences in metabolism of codeine: urinary excretion of codeine glucuronide, morphine-3-glucuronide and morphine-6-glucuronide in mice, rats, guinea pigs and rabbits Xenobiotica 20 1990 683 688
110. S. Ohno, and S. Nakajin Determination of mRNA expression of human UDP glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction Drug Metabolism and Disposition 37 2009 32 40
111. T.N. Operaña, and R.H. Tukey Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation Journal of Biological Chemistry 282 2007 4821 4829
112. R.D.M. Page TreeView: an application to display phylogenetic trees on personal computers Computer Applications in the Biosciences 12 1996 357 358
113. D. Paul, K.M. Standifer, C.E. Inturrisi, and G.W. Pasternak Pharmacological characterization of morphine-6 beta-glucuronide, a very potent morphine metabolite Journal of Pharmacology and Experimental Therapeutics 251 1989 477 483
114. C.J. Peer, T.M. Sissung, A. Kim, L. Jain, S. Woo, and E.R. Gardner Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia Clinical Cancer Research 18 2012 2099 2107
115. M. Pirmohamed, S. James, S. Meakin, C. Green, A.K. Scott, and T.J. Walley Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients British Medical Journal 329 2004 15 19
116. T.M. Polasek, F.P.Y. Lin, J.O. Miners, and M.P. Doogue Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment British Journal of Clinical Pharmacology 71 2011 727 736
117. D.M. Qato, G.C. Alexander, R.M. Conti, M. Johnson, P. Schumm, and S.T. Lindau Use of prescription and over-the-counter and dietary supplements among older adults in the United States The Journal of the American Medical Association 300 2008 2867 2878
118. A. Radominska, J. Little, J.S. Pyrek, R.R. Drake, Y. Igari, and S. Fournel-Gigleux A novel UDP-Glc-specific glucosyltransferase catalyzing the biosynthesis of 6-Oglucosides of bile acids in human liver microsomes Journal of Biological Chemistry 268 1993 15127 15135
119. A. Radominska-Pandya, P.J. Czernik, J.M. Little, E. Battaglia, and P.I. Mackenzie Structural and functional studies of UDP-glucuronosyltransferases Drug Metabolism Reviews 31 1999 817 899
120. J.M. Rae, M.D. Johnson, M.E. Lippman, and D.A. Flockhart Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays Journal of Pharmacology and Experimental Therapeutics 299 2001 849 857
121. P. Raungrut, V. Uchaipichat, D.J. Elliot, B. Janchawee, A.A. Somogyi, and J.O. Miners In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans Journal of Pharmacology and Experimental Therapeutics 334 2010 609 618
122. A. Rowland, D.J. Elliot, J.A. Williams, P.I. Mackenzie, R.G. Dickenson, and J.O. Miners In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction Drug Metabolism and Disposition 34 2006 1055 1062
123. A. Rowland, P. Gaganis, D.J. Elliot, P.I. Mackenzie, K.M. Knights, and J.O. Miners Binding of inhibitory fatty acids is responsible for the enhancement of UPD-glucuronosyltransferase 2B7 activity by albumin Journal of Pharmacology and Experimental Therapeutics 321 2007 137 147
124. A. Rowland, K.M. Knights, P.I. Mackenzie, and Miners J.O. The 'albumin effect' and drug glucuronidation: bovine serum albumin and fatty acid free serum albumin enhance the glucuronidation of UGT1A9 substrates but not UGT1A1 and UGT1A6 activities Drug Metabolism and Disposition 36 2008 1056 1062
125. J. Sahai, K. Gallicano, A. Pakuts, and D.W. Cameron Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus Journal of Infectious Diseases 169 1994 1103 1107
126. S.B. Senafi, D.J. Clarke, and B. Burchell Investigation of the substrate specificity of a cloned expressed human bilirubin UDP-glucuronosyltransferase: UDP-sugar specificity and involvement in steroid and xenobiotic glucuronidation Biochemical Journal 303 1994 233 240
127. K. Senekeo-Effenberger, S. Chen, E. Brace-Sinnokrak, J.A. Bonzo, M.F. Yueh, and U. Argikar Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor alpha activation Drug Metabolism and Disposition 35 2007 419 427
128. T. Shiraga, K. Yajima, K. Suzuki, T. Hashimoto, I. Iwatsubo, and A. Miyashita Identification of UDP-glucuronosyltransferases responsible for the glucuronidation of darexaban, an oral factor Xa inhibitor, in human liver and intestine Drug Metabolism and Disposition 40 2012 276 282
129. M.J. Sorich, R.A. McKinnon, J.O. Miners, and P.A. Smith The importance of local chemical structures for chemical metabolism by human uridine 5′-diphosphate-glucuronosyltransferase Journal of Chemical Information and Modeling 46 2006 2692 2697
130. C.P. Strassburg, A. Strassburg, S. Kneip, A. Barut, R.H. Tukey, and B. Rodeck Developmental aspects of human hepatic drug glucuronidation in young children and adults Gut 50 2002 259 265
131. J. Sugatani, H. Kojima, A. Ueda, S. Kakizaki, K. Yoshinari, and Q.H. Gong The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR Hepatology 33 2001 1232 1238
132. J. Sugatani, K. Yamakawa, E. Tonda, S. Nishitani, K. Yoshinari, and M. Degawa The induction of human UDP-glucuronosyltransferase 1A1 mediated through a distal enhancer module by flavonoids and xenobiotics Biochemical Pharmacology 67 2004 989 1000
133. D. Sun, G. Chen, R.W. Dellinger, A.K. Sharma, and P. Lazarus Characterization of 17-dihydroexemestane glucuronidation: potential role of the UGT2B17 deletion in exemestane pharmacogenetics Pharmacogenetics and Genomics 20 2010 575 585
134. J.M. Sutherland Fatal cardiovascular collapse of infants receiving large amounts of chloramphenicol Archives of Pediatrics and Adolescent Medicine 97 1959 761 767
135. B.K. Tang Drug glucosidation Pharmacology and Therapeutics 46 1990 53 56
136. P. Tsoutsikos, J.O. Miners, A. Stapleton, A. Thomas, B.C. Sallustio, and K.M. Knights Evidence that unsaturated fatty acids are potent inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes and recombinant UGT1A9 and UGT2B7 Biochemical Pharmacology 67 2004 191 199
137. R.H. Tukey, and C.P. Strassburg Human UDP-glucuronosyltransferases: metabolism, expression and disease Annual Review of Pharmacology and Toxicology 40 2000 581 616
138. V. Uchaipichat, P.I. Mackenzie, X.H. Guo, D. Gardner-Stephen, A. Galetin, and J.B. Houston Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid Drug Metabolism and Disposition 32 2004 413 423
139. V. Uchaipichat, L.K. Winner, P.I. Mackenzie, D.J. Elliot, J.A. Williams, and J.O. Miners Quantitative prediction of in vivo inhibitory interactions involving glucuronidated drugs from in vitro data: the effect of fluconazole on zidovudine glucuronidation British Journal of Clinical Pharmacology 61 2006 427 439
140. V. Uchaipichat, A. Galetin, J.B. Houston, P.I. Mackenzie, J.A. Williams, and J.O. Miners Kinetic modeling of the interactions between 4-methylumbelliferone, 1-naphthol, and zidovudine glucuronidation by UDP-glucuronosyltransferase 2B7 (UGT2B7) provides evidence for multiple substrate binding and effector sites Molecular Pharmacology 74 2008 1152 1162
141. V. Uchaipichat, P. Raungrut, N. Chau, B. Janchawee, A.M. Evans, and J.O. Miners Effects of ketamine on human UDP-glucuronosyltransferases in vitro predict potential drug-drug interactions arising from ketamine inhibition of codeine and morphine glucuronidation Drug Metabolism and Disposition 39 2011 1324 1328
142. W. Udomuksorn, D.J. Elliot, B.C. Lewis, P.I. Mackenzie, K. Yoovathaworn, and J.O. Miners Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates Pharmacogenetics and Genomics 17 2007 1017 1029
143. R. Vanholder, R. De Smet, G. Glorieux, A. Argilés, U. Baurmeister, and P. Brunet Review on uremic toxins: classification, concentration, and interindividual variability Kidney International 63 2003 1934 1943
144. R.K. Verbeeck, S.M. Wallace, and G.R. Loewen Reduced elimination of ketoprofen in the elderly is not necessarily due to impaired glucuronidation British Journal of Clinical Pharmacology 17 2012 783 784
145. M. Verreault, K. Senekeo-Effenberger, J. Trottier, J.A. Bonzo, J. Belanger, and J. Kaeding The liver X-receptor alpha controls hepatic expression of the human bile acid-glucuronidating UGT1A3 enzyme in human cells and transgenic mice Hepatology 44 2006 368 378
146. L. Villeneuve, H. Girard, L.C. Fortier, J.F. Gagne, and C.J. Guillemette Novel functional polymorphisms in the UGT1A7 and UGT1A9 glucuronidating enzymes in Caucasian and African-American subjects and their impact on the metabolism of 7-ethyl-10-hydroxycamptothecin and flavopiridol anticancer drugs Journal of Pharmacology and Experimental Therapeutics 307 2003 117 128
147. W.J. Walters, J. Green, J.S. Weiss, and M.A. Murcko What do medicinal chemists actually make? A 50-year retrospective Journal of Medicinal Chemistry 54 2011 6405 6416
148. Y.H. Wang, M. Trucksis, J.J. McElwee, P.H. Wong, C. Maciolek, and C.D. Thompson UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study Clinical Pharmacology and Therapeutics 92 2012 96 102
149. C.F. Weiss, A.J. Glazko, and J.K. Weston Chloramphenicol in the newborn infant. A physiologic explanation of its toxicity when given in excessive doses New England Journal of Medicine 262 1960 787 794
150. J.A. Williams, R. Hyland, B.C. Jones, D.A. Smith, S. Hurst, and T.C. Goosen Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios Drug Metabolism and Disposition 32 2004 1201 1208
151. W. Wilson, F.P.M. de Villena, B.D. Lyn-Cook, P.K. Chatterjee, T.A. Bell, and D.A. Detwiler Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15 Genomics 84 2004 707 714
152. K. Yamamoto, H. Sato, Y. Fujiyama, Y. Doida, and T. Bamba Contribution of two missense mutations G71R and Y486D of the bilirubin UDP-glycosyltransferase UGT1A1 gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II Biochimica et Biophysica Acta 1406 1998 267 273
153. M.F. Yueh, and R.H. Tukey Nrf2-Keap1 signaling pathway regulates human UGT1A1 expression in vitro and in transgenic UGT1 mice Journal of Biological Chemistry 282 2007 8749 8758
154. M.J. Zaya, R.N. Hines, and J.C. Stevens Epirubicin glucuronidation and UGT2B7 developmental expression Drug Metabolism and Disposition 34 2006 2097 2101
155. X. Zhang, Q.Y. Zhang, D. Liu, T. Su, Y. Weng, and G. Ling Expression of cytochromes P450 and other biotransformation genes in fetal and adult human nasal mucosa Drug Metabolism and Disposition 33 2005 1423 1428