The configuration of the 17-hydroxy group variably influences the glucuronidation of beta-estradiol and epiestradiol by human UDP-glucuronosyltransferases

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Katriina ItäahoMoshe Finel

Abstract

The glucuronidation of 17beta-estradiol (beta-estradiol) and 17alpha-estradiol (epiestradiol) was studied to elucidate how the orientation of the 17-OH group affects conjugation at the 3-OH or the 17-OH of either diastereomer. Recombinant human UDP-glucuronosyltransferases (UGTs) UGT1A1, UGT1A3, UGT1A7, UGT1A8, and UGT1A10 conjugated one or both diastereomers, mainly at the 3-OH. The activity of UGT1A4 was low and unique because it was directed merely toward the 17-OH of both aglycones. UGT1A10 exhibited particularly high estradiol glucuronidation activity, the rate and affinity of which were significantly higher in the case of beta-estradiol than with epiestradiol. UGT1A9 did not catalyze estradiol glucuronidation, but UGT1A9-catalyzed scopoletin glucuronidation was competitively inhibited by beta-estradiol. UGT2B4, UGT2B7, and UGT2B17 exclusively conjugated the estradiols at the 17-OH position in a highly stereoselective fashion. UGT2B4 was specific for epiestradiol; UGT2B7 glucuronidated both diastereomers, with high affinity for epiestradiol, whereas UGT2B17 only glucuronidated beta-estradiol. UGT2B15 glucuronidated both estradiols at the 3-OH, with a strong preference for epiestradiol. Human UGT2A1 and UGT2A2 glucuronidate...Continue Reading

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Citations

Nov 5, 2008·The Journal of Biological Chemistry·Peter I MackenzieRobyn Meech
May 4, 2010·Journal of Biochemistry·Yutaka TakaokaHisahide Nishio
Jan 1, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katriina ItäahoMoshe Finel
Dec 17, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nenad ManevskiMoshe Finel
Jun 13, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Martin PerreaultOlivier Barbier
Mar 5, 2014·Journal of Chemical Information and Modeling·Leo GhemtioHenri Xhaard
Sep 29, 2009·Drug Metabolism Reviews·Kathleen M Knights, John O Miners
Jan 15, 2010·Drug Metabolism Reviews·Peter I MackenzieDione A Gardner-Stephen
Jan 14, 2010·Drug Metabolism Reviews·Jean-Marie HeydelAnne-Marie Le Bon
Aug 12, 2009·Expert Opinion on Drug Metabolism & Toxicology·Yin Cheong WongZhong Zuo
Oct 23, 2014·Drug Metabolism Reviews·Dong Gui HuPeter I Mackenzie
Feb 2, 2016·Drug Metabolism Reviews·Dong Gui HuRobyn Meech
Oct 20, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Margaret O James
Mar 3, 2009·Annals of the New York Academy of Sciences·Philip LazarusDongxiao Sun
Oct 11, 2014·Rapid Communications in Mass Spectrometry : RCM·Jeongmin JooKwang-Hyeon Liu
Mar 26, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Sanna KaivosaariMikko Koskinen
Dec 31, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Darja Gramec SkledarMoshe Finel
Apr 5, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Tuomas RahikainenRisto O Juvonen
Apr 13, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Roland AkoBaojian Wu
Jul 30, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Roope A KallionpääMoshe Finel
Jun 11, 2015·Journal of Clinical Psychopharmacology·Katherine L WisnerStephen R Wisniewski
May 2, 2012·Biochimica Et Biophysica Acta·Paula S Montenegro-MirandaPiter J Bosma
Apr 8, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tonika BohnertUNKNOWN International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Victim Drug-Drug Interactions Working
Jul 31, 2016·The Journal of Pharmacology and Experimental Therapeutics·Douglas F DluzenPhilip Lazarus
Apr 30, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Takamitsu KondoMayumi Ishizuka
Dec 23, 2017·Clinical and Experimental Pharmacology & Physiology·Bao-Xia HeHui Liu
Feb 7, 2019·Physiological Reviews·Robyn MeechPeter I Mackenzie
Sep 9, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kimberly LaphamAmit S Kalgutkar
Nov 26, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hongbo ZhangMoshe Finel
Aug 8, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Taina StenMoshe Finel
Oct 28, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Toshifumi ShiragaTakashi Usui
Jan 22, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Katriina ItäahoMoshe Finel
Feb 24, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert L WalskyTheunis C Goosen
Oct 10, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael A Zientek, Kuresh Youdim
Oct 11, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Johanna TrobergMoshe Finel

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