Biochemical and molecular analysis of carboxylesterase-mediated hydrolysis of cocaine and heroin.

British Journal of Pharmacology
M Jason HatfieldP M Potter

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

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Citations

Mar 27, 2012·Applied Microbiology and Biotechnology·Joana LamegoAna S Coroadinha
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
Dec 4, 2014·American Journal of Physical Anthropology·Emily C WebbFred J Longstaffe
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
Mar 12, 2015·Drug Metabolism and Pharmacokinetics·Shingo OdaMiki Nakajima
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
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
Oct 22, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ragnar ThomsenUNKNOWN INDICES Consortium
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

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