| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 265, Issue 14, 7900-7906, 05, 1990
JK Ritter, YY Sheen and IS Owens
The human cDNA clone, UDPGTh-2, encoding a liver UDP-
glucuronosyltransferase (transferase) was isolated from a lambda gt11 cDNA
library by hybridization to the mouse transferase cDNA clone, UDPGTm-1
(Kimura, T., and Owens, I. S. (1987) Eur. J. Biochem.168, 515- 521). The
two clones have nucleotide sequence identities in the coding region of 74%.
UDPGTh-2 encodes a 529-amino acid protein with an NH2 terminus
membrane-insertion signal peptide and a carboxyl terminus membrane-spanning
region. There are three potential asparagine-linked glycosylation sites at
residues 67, 68, and 315. In order to establish substrate specificity, the
clone was inserted into the pSVL vector (pUDPGTh-2) and expressed in COS-1
cells. The presence of a transferase with Mr congruent to 52,000 in
transfected cells cultured in the presence of [35S]methionine was shown by
immunocomplexed products with goat antimouse transferase IgG (Mackenzie, P.
I., Hjelmeland, L. H., and Owens, I. S. (1984) Arch. Biochem. Biophys. 231,
487-497) and protein A-Sepharose and analysis by sodium dodecyl sulfate-
polyacrylamide gel electrophoresis and autoradiography. The transferase is
a glycoprotein as indicated by a shift in Mr congruent to 3000-4000 when
expressed in the presence of tunicamycin. Sixty potential substrates were
tested using cells transfected with pUDPGTh-2. The order of relative
substrate activity was as follows: 4-hydroxyestrone greater than estriol
greater than 2-hydroxyestriol greater than 4- hydroxyestradiol greater than
6 alpha-hydroxyestriol greater than 5 alpha-androstane-3 alpha,11 beta,17
beta-triol = 5 beta-androstane-3 alpha,11 beta,17 beta-triol. There were
only trace amounts of glucuronidation of 2-hydroxyestrone and
2-hydroxyestradiol, and, in contrast to other cloned transferases, no
glucuronidation of either the primary estrogens/androgens (estrone, 17
beta-estradiol/testosterone, androsterone) or any of the exogenous
substrates tested. A Lineweaver- Burk plot of the effect of
4-hydroxyestrone concentration on the velocity of glucuronidation shows an
apparent Km of 13 microM. The unique specificity of this transferase for
3,4-catechol estrogens and estriol suggests it may play an important role
in regulating the level and activity of these potent and active estrogen
metabolites.
Cloning and expression of human liver UDP-glucuronosyltransferase in COS-1 cells. 3,4-catechol estrogens and estriol as primary substrates
Section on Drug Biotransformation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  N. K. Basu, L. Kole, M. Basu, K. Chakraborty, P. S. Mitra, and I. S. Owens The Major Chemical-detoxifying System of UDP-glucuronosyltransferases Requires Regulated Phosphorylation Supported by Protein Kinase C J. Biol. Chem., August 22, 2008; 283(34): 23048 - 23061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Miyagi and A. C. Collier Pediatric Development of Glucuronidation: The Ontogeny of Hepatic UGT1A4 Drug Metab. Dispos., September 1, 2007; 35(9): 1587 - 1592. [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]
|
|
|
|
 |
|
 Z.-J. Liu, W. J. Lee, and B. T. Zhu Selective Insensitivity of ZR-75-1 Human Breast Cancer Cells to 2-Methoxyestradiol: Evidence for Type II 17{beta}-Hydroxysteroid Dehydrogenase as the Underlying Cause Cancer Res., July 1, 2005; 65(13): 5802 - 5811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saeki, Y. Saito, H. Jinno, T. Tanaka-Kagawa, A. Ohno, S. Ozawa, K. Ueno, S. Kamakura, N. Kamatani, K. Komamura, et al. SINGLE NUCLEOTIDE POLYMORPHISMS AND HAPLOTYPE FREQUENCIES OF UGT2B4 AND UGT2B7 IN A JAPANESE POPULATION Drug Metab. Dispos., September 1, 2004; 32(9): 1048 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Basu, S. Kubota, M. R. Meselhy, M. Ciotti, B. Chowdhury, M. Hartori, and I. S. Owens Gastrointestinally Distributed UDP-glucuronosyltransferase 1A10, Which Metabolizes Estrogens and Nonsteroidal Anti-inflammatory Drugs, Depends upon Phosphorylation J. Biol. Chem., July 2, 2004; 279(27): 28320 - 28329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Turgeon, S. Chouinard, P. Belanger, S. Picard, J.-F. Labbe, P. Borgeat, and A. Belanger Glucuronidation of arachidonic and linoleic acid metabolites by human UDP-glucuronosyltransferases J. Lipid Res., June 1, 2003; 44(6): 1182 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Murata, E. H. Warren, and S. R. Riddell A Human Minor Histocompatibility Antigen Resulting from Differential Expression due to a Gene Deletion J. Exp. Med., May 19, 2003; 197(10): 1279 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Zhang, J. Zhan, C. S. Cook, R. M. Ings, and A. P. Breau Involvement of Human UGT2B7 and 2B15 in Rofecoxib Metabolism Drug Metab. Dispos., May 1, 2003; 31(5): 652 - 658. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. Krishnaswamy, S. X. Duan, L. L. von Moltke, D. J. Greenblatt, and M. H. Court Validation of Serotonin (5-Hydroxtryptamine) as an in Vitro Substrate Probe for Human UDP-Glucuronosyltransferase (UGT) 1A6 Drug Metab. Dispos., January 1, 2003; 31(1): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Collier, M. D. Tingle, J. W. Paxton, M. D. Mitchell, and J. A. Keelan Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption Hum. Reprod., October 1, 2002; 17(10): 2564 - 2572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishii, A. Miyoshi, R. Watanabe, K. Tsuruda, M. Tsuda, Y. Yamaguchi-Nagamatsu, K. Yoshisue, M. Tanaka, D. Maji, S. Ohgiya, et al. 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., November 1, 2001; 60(5): 1040 - 1048. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Guillemette, I. De Vivo, S. E. Hankinson, C. A. Haiman, D. Spiegelman, D. E. Housman, and D. J. Hunter Association of Genetic Polymorphisms in UGT1A1 with Breast Cancer and Plasma Hormone Levels Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 711 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. H. Tukey and C. P. Strassburg Genetic Multiplicity of the Human UDP-Glucuronosyltransferases and Regulation in the Gastrointestinal Tract Mol. Pharmacol., March 1, 2001; 59(3): 405 - 414. [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]
|
|
|
|
|
|
Q. Ren, S. E. Murphy, Z. Zheng, and P. Lazarus O-Glucuronidation of the Lung Carcinogen 4-(methylnitrosamino)-1- (3-Pyridyl)-1-Butanol (nnal) by Human Udp-Glucuronosyltransferases 2b7 and 1a9 Drug Metab. Dispos., November 1, 2000; 28(11): 1352 - 1360. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Raftogianis, C. Creveling, R. Weinshilboum, and J. Weisz Chapter 6: Estrogen Metabolism by Conjugation J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 113 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishii, A. J. Hansen, and P. I. Mackenzie Octamer Transcription Factor-1 Enhances Hepatic Nuclear Factor-1alpha -Mediated Activation of the Human UDP Glucuronosyltransferase 2B7 Promoter Mol. Pharmacol., May 1, 2000; 57(5): 940 - 947. [Abstract] [Full Text]
|
|
|
|
|
|
V. M. Samokyszyn, W. E. Gall, G. Zawada, M. A. Freyaldenhoven, G. Chen, P. I. Mackenzie, T. R. Tephly, and A. Radominska-Pandya 4-Hydroxyretinoic Acid, a Novel Substrate for Human Liver Microsomal UDP-glucuronosyltransferase(s) and Recombinant UGT2B7 J. Biol. Chem., March 15, 2000; 275(10): 6908 - 6914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Lampe, J. Bigler, A. C. Bush, and J. D. Potter Prevalence of Polymorphisms in the Human UDP-Glucuronosyltransferase 2B Family: UGT2B4(D458E), UGT2B7(H268Y), and UGT2B15(D85Y) Cancer Epidemiol. Biomarkers Prev., March 1, 2000; 9(3): 329 - 333. [Abstract] [Full Text]
|
|
|
|
|
|
M. Brangi, T. Litman, M. Ciotti, K. Nishiyama, G. Kohlhagen, C. Takimoto, R. Robey, Y. Pommier, T. Fojo, and S. E. Bates Camptothecin Resistance: Role of the ATP-binding Cassette (ABC), Mitoxantrone-resistance Half-Transporter (MXR), and Potential for Glucuronidation in MXR-expressing Cells Cancer Res., December 1, 1999; 59(23): 5938 - 5946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-H. Woo, M. J. Orbach, A. M. Hirsch, and M. C. Hawes Meristem-Localized Inducible Expression of a UDP-Glycosyltransferase Gene Is Essential for Growth and Development in Pea and Alfalfa PLANT CELL, December 1, 1999; 11(12): 2303 - 2316. [Abstract] [Full Text]
|
|
|
|
|
|
Z. Cheng, A. Radominska-Pandya, and T. R. Tephly Studies on the Substrate Specificity of Human Intestinal UDP-Glucuronosyltransferases 1A8 and 1A10 Drug Metab. Dispos., October 1, 1999; 27(10): 1165 - 1170. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Ciotti, V. M. Lakshmi, N. Basu, B. B. Davis, I. S. Owens, and T. V. Zenser Glucuronidation of benzidine and its metabolites by cDNA-expressed human UDP-glucuronosyltransferases and pH stability of glucuronides Carcinogenesis, October 1, 1999; 20(10): 1963 - 1969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Albert, M. Vallée, G. Beaudry, A. Bélanger, and D. W. Hum The Monkey and Human Uridine Diphosphate-Glucuronosyltransferase UGT1A9, Expressed in Steroid Target Tissues, Are Estrogen-Conjugating Enzymes Endocrinology, July 1, 1999; 140(7): 3292 - 3302. [Abstract] [Full Text]
|
|
|
|
|
|
M. D. Green and T. R. Tephly Glucuronidation of Amine Substrates by Purified and Expressed UDP-Glucuronosyltransferase Proteins Drug Metab. Dispos., September 1, 1998; 26(9): 860 - 867. [Abstract] [Full Text]
|
|
|
|
|
|
B. L. Coffman, C. D. King, G. R. Rios, and T. R. Tephly The Glucuronidation of Opioids, Other Xenobiotics, and Androgens by Human UGT2B7Y(268) and UGT2B7H(268) Drug Metab. Dispos., January 1, 1998; 26(1): 73 - 77. [Abstract] [Full Text]
|
|
|
|
|
|
M. D. Green, G. Bélanger, D. W. Hum, A. Bélanger, and T. R. Tephly Glucuronidation of Opioids, Carboxylic Acid-Containing Drugs, and Hydroxylated Xenobiotics Catalyzed by Expressed Monkey UDP-Glucuronosyltransferase 2B9 Protein Drug Metab. Dispos., December 1, 1997; 25(12): 1389 - 1394. [Abstract] [Full Text]
|
|
|
|
|
|
B. L. Coffman, G. R. Rios, C. D. King, and T. R. Tephly Human UGT2B7 Catalyzes Morphine Glucuronidation Drug Metab. Dispos., January 1, 1997; 25(1): 1 - 4. [Abstract] [Full Text]
|
|
|
|
|
|
M. Beaulieu, E. Levesque, D. W. Hum, and A. Belanger Isolation and Characterization of a Novel cDNA Encoding a Human UDP-Glucuronosyltransferase Active on C19 Steroids J. Biol. Chem., September 13, 1996; 271(37): 22855 - 22862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ciotti, M. T. Yeatman, R. J. Sokol, and I. S. Owens Altered Coding for a Strictly Conserved Di-glycine in the Major Bilirubin UDP-glucuronosyltransferase of a Crigler-Najjar Type I Patient J. Biol. Chem., February 17, 1995; 270(7): 3284 - 3291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Strassburg, S. Kneip, J. Topp, P. Obermayer-Straub, A. Barut, R. H. Tukey, and M. P. Manns Polymorphic Gene Regulation and Interindividual Variation of UDP-glucuronosyltransferase Activity in Human Small Intestine J. Biol. Chem., November 10, 2000; 275(46): 36164 - 36171. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
