HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M300010-JLR200v1 44/6/1182    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Turgeon, D. Articles by Bélanger, A. Search for Related Content PubMed PubMed Citation Articles by Turgeon, D. Articles by Bélanger, A. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 44, 1182-1191, June 2003
Copyright © 2003 by Lipid Research, Inc.

Glucuronidation of arachidonic and linoleic acid metabolites by human UDP-glucuronosyltransferases

David Turgeon^*, Sarah Chouinard^*, Patrick Bélanger^*, Serge Picard, Jean-François Labbé, Pierre Borgeat and Alain Bélanger^1,*

^* Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Laval University, Québec, Canada
Immunology and Rheumatology Research Center, CHUL Research Center, Laval University, Québec, Canada

¹ To whom correspondence should be addressed. e-mail: alain.belanger{at}crchul.ulaval.ca

Arachidonic acids (AA) and linoleic acids (LAs) are metabolized, in several tissues, to hydroxylated metabolites that are important mediators of many physiological and pathophysiological processes. The conjugation of leukotriene B₄ (LTB₄), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, and 13-hydroxyoctadecadienoic acid (HODE) by the human UDP-glucuronosyltransferase (UGT) enzymes was investigated. All substrates tested were efficiently conjugated by human liver microsomes to polar derivatives containing the glucuronyl moiety as assessed by mass spectrometry. The screening analyses with stably expressed UGT enzymes in HK293 showed that glucuronidation of LTB₄ was observed with UGT1A1, UGT1A3, UGT1A8, and UGT2B7, whereas UGT1A1, UGT1A3, UGT1A4, and UGT1A9 also conjugated most of the HETEs and 13-HODE. LA and AA metabolites also appear to be good substrates for the UGT2B subfamily members, especially for UGT2B4 and UGT2B7 that conjugate all HETE and 13-HODE. Interestingly, UGT2B10 and UGT2B11, which are considered as orphan enzymes since no conjugation activity has so far been demonstrated with these enzymes, conjugated 12-HETE, 15-HETE, and 13-HODE.

In summary, our data showed that several members of UGT1A and UGT2B families are capable of converting LA and AA metabolites into glucuronide derivatives, which is considered an irreversible step to inactivation and elimination of endogenous substances from the body.

Supplementary key words eicosanoid • polyunsaturated fatty acid • leukotriene B₄

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Chouinard, O. Barbier, and A. Belanger UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 Enzymes Are Major Determinants of the Androgen Response in Prostate Cancer LNCaP Cells J. Biol. Chem., November 16, 2007; 282(46): 33466 - 33474. [Abstract] [Full Text] [PDF]

				S. Kaivosaari, P. Toivonen, L. M. Hesse, M. Koskinen, M. H. Court, and M. Finel Nicotine Glucuronidation and the Human UDP-Glucuronosyltransferase UGT2B10 Mol. Pharmacol., September 1, 2007; 72(3): 761 - 768. [Abstract] [Full Text] [PDF]

				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 UDP-Glucuronosyltransferase 2B7 Activity by Albumin: Implications for in Vitro-in Vivo Extrapolation J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 137 - 147. [Abstract] [Full Text] [PDF]

				K. Senekeo-Effenberger, S. Chen, E. Brace-Sinnokrak, J. A. Bonzo, M.-F. Yueh, U. Argikar, J. Kaeding, J. Trottier, R. P. Remmel, J. K. Ritter, et al. 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 Metab. Dispos., March 1, 2007; 35(3): 419 - 427. [Abstract] [Full Text] [PDF]

				S. Chouinard, G. Pelletier, A. Belanger, and O. Barbier Isoform-Specific Regulation of Uridine Diphosphate-Glucuronosyltransferase 2B Enzymes in the Human Prostate: Differential Consequences for Androgen and Bioactive Lipid Inactivation Endocrinology, November 1, 2006; 147(11): 5431 - 5442. [Abstract] [Full Text] [PDF]

				S. Chouinard, M. Tessier, G. Vernouillet, S. Gauthier, F. Labrie, O. Barbier, and A. Belanger Inactivation of the Pure Antiestrogen Fulvestrant and Other Synthetic Estrogen Molecules by UDP-Glucuronosyltransferase 1A Enzymes Expressed in Breast Tissue Mol. Pharmacol., March 1, 2006; 69(3): 908 - 920. [Abstract] [Full Text] [PDF]

				J. Jakobsson, L. Ekstrom, N. Inotsume, M. Garle, M. Lorentzon, C. Ohlsson, H.-K. Roh, K. Carlstrom, and A. Rane Large Differences in Testosterone Excretion in Korean and Swedish Men Are Strongly Associated with a UDP-Glucuronosyl Transferase 2B17 Polymorphism J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 687 - 693. [Abstract] [Full Text] [PDF]

				D. French, M. R. Wilkinson, W. Yang, L. de Chaisemartin, E. H. Cook, S. Das, M. J. Ratain, W. E. Evans, J. R. Downing, C.-H. Pui, et al. Global gene expression as a function of germline genetic variation Hum. Mol. Genet., June 15, 2005; 14(12): 1621 - 1629. [Abstract] [Full Text] [PDF]

				J. M. Little, M. Kurkela, J. Sonka, S. Jantti, R. Ketola, S. Bratton, M. Finel, and A. Radominska-Pandya Glucuronidation of oxidized fatty acids and prostaglandins B1 and E2 by human hepatic and recombinant UDP-glucuronosyltransferases J. Lipid Res., September 1, 2004; 45(9): 1694 - 1703. [Abstract] [Full Text] [PDF]

				D. E. Blask, R. T. Dauchy, L. A. Sauer, and J. A. Krause Melatonin uptake and growth prevention in rat hepatoma 7288CTC in response to dietary melatonin: melatonin receptor-mediated inhibition of tumor linoleic acid metabolism to the growth signaling molecule 13-hydroxyoctadecadienoic acid and the potential role of phytomelatonin Carcinogenesis, June 1, 2004; 25(6): 951 - 960. [Abstract] [Full Text] [PDF]