![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 28, Issue 5, 497-502, May 2000
Laboratory of Molecular Endocrinology (O.B., D.T., C.G., D.W.H.)
and MRC Group in Molecular Endocrinology (A.B.), CHUL Research Center,
Laval University, Quebec, Canada; and Department of Pharmacology,
University of Iowa, Iowa City, Iowa (M.D.G., T.R.T.)
3'-Azido-3'-deoxythymidine (AZT) is frequently prescribed to
patients infected with the human immunodeficiency virus. After absorption, AZT is rapidly metabolized into
3'-azido-3'-deoxy-5'-glucuronylthymidine by UDP-glucuronosyltransferase
(UGT) enzymes. Using labeled [14C]UDP-glucuronic acid and
microsomal preparations from human kidney 293 cells stably
expressing the different human UGT2B isoenzymes, it was demonstrated
that AZT glucuronidation is catalyzed specifically by human UGT2B7. The
identity of the metabolite formed was confirmed as AZT-G by liquid
chromatography coupled with mass spectrometry. UGT2B7 is encoded by a
polymorphic gene and kinetic analysis of AZT glucuronidation by the two
allelic variants UGT2B7(H268) and UGT2B7(Y268),
yielded apparent Km values of 91.0 and 80.1 µM, respectively. Normalization to protein levels yielded
glucuronidation efficiency ratios
(Vmax/Km) of 21.3 and 11.0 µl · min
1 · mg protein1
for UGT2B7(H268) and UGT2B7(Y268),
respectively. It remains possible that other UGT enzymes are also
involved in AZT conjugation; however, the glucuronidation of AZT by
UGT2B7, which is a UGT2B protein expressed in the liver, is consistent
with previous findings and supports the physiological relevance of this
enzyme in AZT conjugation.
This article has been cited by other articles:
|
|
 |
|
  Z. Wen, D. E. Martin, P. Bullock, K.-H. Lee, and P. C. Smith Glucuronidation of Anti-HIV Drug Candidate Bevirimat: Identification of Human UDP-glucuronosyltransferases and Species Differences Drug Metab. Dispos., March 1, 2007; 35(3): 440 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bowalgaha, D. J. Elliot, P. I. Mackenzie, K. M. Knights, and J. O. Miners The Glucuronidation of {Delta}4-3-Keto C19- and C21-Hydroxysteroids by Human Liver Microsomal and Recombinant UDP-glucuronosyltransferases (UGTs): 6{alpha}- and 21-Hydroxyprogesterone Are Selective Substrates for UGT2B7 Drug Metab. Dispos., March 1, 2007; 35(3): 363 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Bernard, J. Tojcic, K. Journault, L. Perusse, and C. Guillemette Influence of Nonsynonymous Polymorphisms of UGT1A8 and UGT2B7 Metabolizing Enzymes on the Formation of Phenolic and Acyl Glucuronides of Mycophenolic Acid Drug Metab. Dispos., September 1, 2006; 34(9): 1539 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Xu, D. M. Krenitsky, A. M. Seacat, J. L. Butenhoff, T. R. Tephly, and M. W. Anders N-GLUCURONIDATION OF PERFLUOROOCTANESULFONAMIDE BY HUMAN, RAT, DOG, AND MONKEY LIVER MICROSOMES AND BY EXPRESSED RAT AND HUMAN UDP-GLUCURONOSYLTRANSFERASES Drug Metab. Dispos., August 1, 2006; 34(8): 1406 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Thibaudeau, J. Lepine, J. Tojcic, Y. Duguay, G. Pelletier, M. Plante, J. Brisson, B. Tetu, S. Jacob, L. Perusse, et al. Characterization of Common UGT1A8, UGT1A9, and UGT2B7 Variants with Different Capacities to Inactivate Mutagenic 4-Hydroxylated Metabolites of Estradiol and Estrone Cancer Res., January 1, 2006; 66(1): 125 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Engtrakul, R. S. Foti, T. J. Strelevitz, and M. B. Fisher ALTERED AZT (3'-AZIDO-3'-DEOXYTHYMIDINE) GLUCURONIDATION KINETICS IN LIVER MICROSOMES AS AN EXPLANATION FOR UNDERPREDICTION OF IN VIVO CLEARANCE: COMPARISON TO HEPATOCYTES AND EFFECT OF INCUBATION ENVIRONMENT Drug Metab. Dispos., November 1, 2005; 33(11): 1621 - 1627. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kaji and T. Kume REGIOSELECTIVE GLUCURONIDATION OF DENOPAMINE: MARKED SPECIES DIFFERENCES AND IDENTIFICATION OF HUMAN UDP-GLUCURONOSYLTRANSFERASE ISOFORM Drug Metab. Dispos., March 1, 2005; 33(3): 403 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Garland, K. M. Abildskov, T.-w. Kiu, S. S. Daniel, and R. I. Stark THE CONTRIBUTION OF FETAL METABOLISM TO THE DISPOSITION OF MORPHINE Drug Metab. Dispos., January 1, 2005; 33(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Picard, D. Ratanasavanh, A. Premaud, Y. Le Meur, and P. Marquet IDENTIFICATION OF THE UDP-GLUCURONOSYLTRANSFERASE ISOFORMS INVOLVED IN MYCOPHENOLIC ACID PHASE II METABOLISM Drug Metab. Dispos., January 1, 2005; 33(1): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Zapor, K. L. Cozza, G. H. Wynn, G. W. Wortmann, and S. C. Armstrong Antiretrovirals, Part II: Focus on Non-Protease Inhibitor Antiretrovirals (NRTIs, NNRTIs, and Fusion Inhibitors) Psychosomatics, December 1, 2004; 45(6): 524 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rodriguez-Melendez, J. B. Griffin, and J. Zempleni Biotin Supplementation Increases Expression of the Cytochrome P450 1B1 Gene in Jurkat Cells, Increasing the Occurrence of Single-Stranded DNA Breaks J. Nutr., September 1, 2004; 134(9): 2222 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Collier, J. A. Keelan, P. E. van Zijl, J. W. Paxton, M. D. Mitchell, and M. D. Tingle HUMAN PLACENTAL GLUCURONIDATION AND TRANSPORT OF 3'AZIDO-3'-DEOXYTHYMIDINE AND URIDINE DIPHOSPHATE GLUCURONIC ACID Drug Metab. Dispos., August 1, 2004; 32(8): 813 - 820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Court, Q. Hao, S. Krishnaswamy, T. Bekaii-Saab, A. Al-Rohaimi, L. L. von Moltke, and D. J. Greenblatt UDP-Glucuronosyltransferase (UGT) 2B15 Pharmacogenetics: UGT2B15 D85Y Genotype and Gender Are Major Determinants of Oxazepam Glucuronidation by Human Liver J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 656 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhang, W. Zhao, V. A. Roongta, J. G. Mitroka, L. J. Klunk, and M. Zhu AMIDE N-GLUCURONIDATION OF MAXIPOST CATALYZED BY UDP-GLUCURONOSYLTRANSFERASE 2B7 IN HUMANS Drug Metab. Dispos., May 1, 2004; 32(5): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Uchaipichat, P. I. Mackenzie, X.-H. Guo, D. Gardner-Stephen, A. Galetin, J. B. Houston, and J. O. Miners 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 Metab. Dispos., April 1, 2004; 32(4): 413 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Rudek, J. Venitz, Y. Ando, E. Reed, J. M. Pluda, and W. D. Figg Factors Involved in the Pharmacokinetics of COL-3, a Matrix Metalloproteinase Inhibitor, in Patients with Refractory Metastatic Cancer: Clinical and Experimental Studies J. Clin. Pharmacol., October 1, 2003; 43(10): 1124 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Court, S. Krishnaswamy, Q. Hao, S. X. Duan, C. J. Patten, L. L. von Moltke, and D. J. Greenblatt 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 Metab. Dispos., September 1, 2003; 31(9): 1125 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Girard, O. Barbier, G. Veilleux, M. El-Alfy, and A. Belanger Human Uridine Diphosphate-Glucuronosyltransferase UGT2B7 Conjugates Mineralocorticoid and Glucocorticoid Metabolites Endocrinology, June 1, 2003; 144(6): 2659 - 2668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Turgeon, J.-S. Carrier, S. Chouinard, and A. Belanger Glucuronidation Activity of the UGT2B17 Enzyme toward Xenobiotics Drug Metab. Dispos., May 1, 2003; 31(5): 670 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Iyer, M. N. Ho, W. M. Shinn, W. W. Bradford, M. J. Tanga, S. S. Nath, and C. E. Green Glucuronidation of 1'-Hydroxyestragole (1'-HE) by Human UDP-Glucuronosyltransferases UGT2B7 and UGT1A9 Toxicol. Sci., May 1, 2003; 73(1): 36 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Coffman, W. R. Kearney, S. Goldsmith, B. M. Knosp, and T. R. Tephly Opioids Bind to the Amino Acids 84 to 118 of UDP-Glucuronosyltransferase UGT2B7 Mol. Pharmacol., February 1, 2003; 63(2): 283 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. V. Capparelli, J. A. Englund, J. D. Connor, S. A. Spector, R. E. McKinney, P. Palumbo, C. J. Baker, and the PACTG 152 Team Population Pharmacokinetics and Pharmacodynamics of Zidovudine in HIV-Infected Infants and Children J. Clin. Pharmacol., February 1, 2003; 43(2): 133 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Rios and T. R. Tephly Inhibition and Active Sites of UDP-Glucuronosyltransferases 2B7 and 1A1. Drug Metab. Dispos., December 1, 2002; 30(12): 1364 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Court, S. X. Duan, C. Guillemette, K. Journault, S. Krishnaswamy, L. L. von Moltke, and D. J. Greenblatt 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., November 1, 2002; 30(11): 1257 - 1265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Toide, Y. Takahashi, H. Yamazaki, Y. Terauchi, T. Fujii, A. Parkinson, and T. Kamataki Hepatocyte Nuclear Factor-1alpha Is a Causal Factor Responsible for Interindividual Differences in the Expression of UDP-Glucuronosyltransferase 2B7 mRNA in Human Livers Drug Metab. Dispos., June 1, 2002; 30(6): 613 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Armstrong, K. L. Cozza, and J. R. Oesterheld Med-Psych Drug-Drug Interactions Update Psychosomatics, February 1, 2002; 43(1): 77 - 81. [Full Text]
|
|
|
|
|
|
B. L. Coffman, W. R. Kearney, M. D. Green, R. G. Lowery, and T. R. Tephly Analysis of Opioid Binding to UDP-Glucuronosyltransferase 2B7 Fusion Proteins Using Nuclear Magnetic Resonance Spectroscopy Mol. Pharmacol., June 1, 2001; 59(6): 1464 - 1469. [Abstract] [Full Text]
|
|
|
|
|
|
D. Turgeon, J.-S. Carrier, E. Levesque, D. W. Hum, and A. Belanger Relative Enzymatic Activity, Protein Stability, and Tissue Distribution of Human Steroid-Metabolizing UGT2B Subfamily Members Endocrinology, February 1, 2001; 142(2): 778 - 787. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
