The regio- and stereo-selectivity of C19 and C21 hydroxysteroid glucuronidation by UGT2B7 and UGT2B11

Archives of Biochemistry and Biophysics
C J JinJ O Miners

Abstract

The capacity of two human hepatic UDP-glucuronosyltransferase (UGT) isoforms, UGT2B7 and UGT2B11, to metabolize more than 50 hydroxylated androgens and pregnanes was investigated. All mono- and dihydroxylated androgens with a hydroxyl function in the 3 alpha, 6 alpha, and 17 beta positions were glucuronidated by UGT2B7, but highest activity was generally observed for steroids containing a 3 alpha-hydroxy substituent. UGT2B7 did not glucuronidate 2 alpha-, 2 beta-, 3 beta-, 6 beta-, 7 alpha-, 11 alpha-, and 11 beta-monohydroxylated androgens, although the presence of hydroxyl groups at certain of these positions did not abolish the ability of UGT2B7 to metabolize diols which also possessed a 3 alpha- or 17 beta-hydroxyl group. 3 alpha-Hydroxypregnanes were also glucuronidated by UGT2B7. Activity was not detected for 6 alpha-, 6 beta-, 11 beta-, 12 alpha-, 16 alpha-, 17 alpha-, 20 alpha-, or 21-monohydroxylated pregnanes. Although 11 alpha-hydroxylated androgens were not glucuronidated by UGT2B7, this enzyme exhibited high activity toward the 11 alpha-hydroxylated derivatives of 5 beta-prenanedione and progesterone. UGT2B11 similarly glucuronidated 3 alpha-hydroxyandrogens and -pregnanes, but rates of metabolism were low compared...Continue Reading

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Citations

Jul 5, 2011·Journal of Bacteriology·Yann-Lii LeuYin-Ru Chiang
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·R H Tukey, C P Strassburg
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·John O MinersPeter I Mackenzie
Nov 30, 2000·Clinical Chemistry and Laboratory Medicine : CCLM·P I MackenzieR A McKinnon
Mar 19, 2013·The International Journal of Biochemistry & Cell Biology·Andrew RowlandPeter I Mackenzie
Nov 27, 1999·Drug Metabolism Reviews·A Radominska-PandyaP I Mackenzie
Oct 23, 2014·Drug Metabolism Reviews·Dong Gui HuPeter I Mackenzie
Feb 21, 2002·Biochemical Pharmacology·Abby C CollierJeffrey A Keelan
Oct 15, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Michael H CourtMoshe Finel
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
Mar 25, 2014·Applied and Environmental Microbiology·Po-Hsiang WangYin-Ru Chiang
Feb 7, 2019·Physiological Reviews·Robyn MeechPeter I Mackenzie
Oct 25, 2008·Psychopharmacology·Helena HedströmTorbjörn Bäckström
Jun 20, 2003·The Pharmacogenomics Journal·C Guillemette
Feb 4, 2003·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Brian Burchell
Aug 8, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Taina StenMoshe Finel
Oct 4, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Vincent MénardChantal Guillemette
Aug 16, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tiia KuuranneRisto Kostiainen
Mar 28, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew RowlandJohn O Miners
Feb 20, 2007·The Journal of Biological Chemistry·Yin-Ru ChiangGeorg Fuchs
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Jul 20, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Noriyuki KasaiKuniyo Inouye

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