Abstract
Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11. The hydrolysis of heroin and cocaine by recombinant human CEs was evaluated and the kinetic parameters determined. In addition, microsomal samples prepared from these tissues were subjected to chromatographic separation, and substrate hydrolysis and amounts of different CEs were determined. In contrast to previous reports, cocaine was not hydrolysed by the human liver CE, hCE1 (CES1), either as highly active recombinant protein or as CEs isolated from human liver or intestinal extracts. These results correlated well with computer-assisted molecular modelling studies that suggested that hydrolysis of cocaine by hCE1 (CES1), would be unlikely to occur. However, cocaine, heroin and CPT-11 were all substrates for the intestinal CE, hiCE (CES2), as determined using both the recombinant protein and the tissue fractions. Again, these data were in agreement with the modelling results. These results indicate that the human liver CE is unlikely to pla...Continue Reading
References
May 1, 1977·Life Sciences·D J StewartW Kalow
Feb 1, 1990·Journal of Neurochemistry·S J GatleyD J Schlyer
Apr 1, 1974·The Journal of Cell Biology·H BeaufayJ Berthet
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Apr 7, 1997·Biochemical and Biophysical Research Communications·H SchwerG Schmitz
Jun 6, 1997·The Journal of Biological Chemistry·E V PindelW F Bosron
Oct 16, 1999·FEBS Letters·M MoriK Chiba
Nov 26, 1999·Molecular Pharmacology·H M Dodds, L P Rivory
Mar 17, 2001·Molecular Biotechnology·C L Morton, P M Potter
Jul 17, 2001·Molecular Pharmacology·R M WadkinsP M Potter
Apr 8, 2003·Nature Structural Biology·Sompop BencharitMatthew R Redinbo
May 3, 2003·Chemistry & Biology·Sompop BencharitMatthew R Redinbo
Jul 2, 2003·Pharmacogenetics·Michael H WuM Eileen Dolan
Jan 1, 1963·Advances in Enzyme Regulation·H SCHIMASSEKT BUECHER
Oct 10, 2003·Clinical Pharmacology and Therapeutics·François GirardinKarin Fattinger
May 25, 2004·Molecular Pharmacology·Randy M WadkinsPhilip M Potter
Jul 23, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Toshiki TabataTsuyoshi Yokoi
Mar 8, 2005·Drug Discovery Today·Matthew R Redinbo, Philip M Potter
Apr 15, 2005·Journal of Medicinal Chemistry·Randy M WadkinsPhilip M Potter
Aug 6, 2005·Journal of Molecular Biology·Christopher D FlemingMatthew R Redinbo
Aug 19, 2005·Journal of Medicinal Chemistry·Janice L HyattPhilip M Potter
Jan 24, 2006·Journal of Chemical Information and Modeling·Hongming ChenJin Li
Apr 14, 2006·Current Medicinal Chemistry·Philip M Potter, Randy M Wadkins
Sep 12, 2006·Journal of Molecular Biology·Sompop BencharitMatthew R Redinbo
Oct 19, 2007·Journal of Medicinal Chemistry·Janice L HyattPhilip M Potter
Jan 12, 2008·Cancer Gene Therapy·M WierdlP M Potter
May 20, 2008·American Journal of Human Genetics·Hao-Jie ZhuJohn S Markowitz
Jun 19, 2009·Journal of Medicinal Chemistry·Latorya D HicksPhilip M Potter
Citations
Mar 27, 2012·Applied Microbiology and Biotechnology·Joana LamegoAna S Coroadinha
Dec 1, 2011·Journal of Molecular Modeling·Xiaozhen YuRandy M Wadkins
Dec 14, 2011·Pharmaceutical Research·Jenna A RhoadesJohn S Markowitz
Jan 5, 2013·Journal of Natural Products·M Jason HatfieldPhilip M Potter
Feb 4, 2012·Future Medicinal Chemistry·David A Gorelick
Jul 23, 2014·Forensic Science International : Synergy·C H ThaulowJ Mørland
May 26, 2011·Expert Opinion on Therapeutic Patents·M Jason Hatfield, Philip M Potter
Nov 22, 2011·Toxicology and Applied Pharmacology·J Allen CrowMatthew K Ross
Dec 4, 2014·American Journal of Physical Anthropology·Emily C WebbFred J Longstaffe
Dec 3, 2014·Protein Expression and Purification·Usa BoonyuenMallika Imwong
Nov 6, 2012·Chemico-biological Interactions·Lyudmila G TsurkanPhilip M Potter
May 24, 2015·Forensic Science International : Synergy·Maria AnderssonOlof Beck
Dec 3, 2014·Toxicology Letters·Markus R MeyerHans H Maurer
Apr 22, 2014·Journal of Proteomics·Eva Rodríguez-SuárezJuan M Falcón-Pérez
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
Apr 27, 2016·Drug and Alcohol Dependence·Kayla N EllefsenMarilyn A Huestis
Mar 24, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Armel StockisJean-Marie Nicolas
May 1, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Levente SzöcsBéla Noszál
Nov 5, 2016·The AAPS Journal·Upendra A ArgikarPunit H Marathe
Jul 17, 2016·British Journal of Pharmacology·Monika WierdlPhilip M Potter
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shujuan ChenRobert H Tukey
Jan 26, 2016·PloS One·Danuta Kowalczyk-PachelElżbieta Lorenc-Koci
Jan 24, 2017·Journal of Medicinal Chemistry·M Jason HatfieldPhilip M Potter
Oct 22, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ragnar ThomsenUNKNOWN INDICES Consortium
Nov 25, 2020·Analytical Methods : Advancing Methods and Applications·Masanori MineToshio Takayanagi
Mar 3, 2018·European Journal of Medicinal Chemistry·Randall J BinderPhilip M Potter
May 1, 2021·Nature Chemical Biology·Jarrett R RemsbergBenjamin F Cravatt
Jun 26, 2021·Drug Metabolism and Pharmacokinetics·Kaori YasudaToshiyuki Sakaki
Jul 14, 2021·ACS Chemical Neuroscience·Mingliang LinKim D Janda
Nov 6, 2010·Chemical Research in Toxicology·Shuqi XieMatthew K Ross
Oct 24, 2018·Journal of Natural Products·M Jason HatfieldPhilip M Potter