DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xie, M.
Right arrow Articles by Yan, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xie, M.
Right arrow Articles by Yan, B.

Vol. 30, Issue 5, 541-547, May 2002

Human and Rodent Carboxylesterases: Immunorelatedness, Overlapping Substrate Specificity, Differential Sensitivity to Serine Enzyme Inhibitors, and Tumor-Related Expression

Mingxing Xie, Dongfang Yang, Lan Liu, Bob Xue, and Bingfang Yan

Department of Biomedical Sciences, University of Rhode Island, Kingston, Rhode Island

Carboxylesterases hydrolyze numerous endogenous and foreign compounds with diverse structures. Humans and rodents express multiple forms of carboxylesterases, which share a high degree of sequence identity (~70%). Alignment analyses locate in carboxylesterases several functional subsites such the catalytic triad as seen in acetylcholinesterase. The aim of this study was to determine among human and rodent carboxylesterases the immunorelatedness, overlapping substrate specificity, differential sensitivity to serine enzyme inhibitors, tissue distribution, and tumor-related expression. Six antibodies against whole carboxylesterases or synthetic peptides were tested for their reactivity toward 11 human or rodent recombinant carboxylesterases. The antibodies against whole proteins generally exhibited a broader cross-reactivity than the anti-peptide antibodies. All carboxylesterases hydrolyzed para-nitrophenylacetate and para-nitrophenylbutyrate. However, the relative activity varied markedly from enzyme to enzyme (>20-fold), and some carboxylesterases showed a clear substrate preference. Carboxylesterases with the same functional subsites had a similar profile on substrate specificity and sensitivity toward phenylmethylsulfonyl fluoride (PMSF) and paraoxon, suggesting that these subsites play determinant roles in the recognition of substrates and inhibitors. Among three human carboxylesterases, HCE-1 hydrolyzed both substrates to a similar extent, whereas HCE-2 and HCE-3 showed an opposite substrate preference. All three enzymes were inhibited by PMSF and paraoxon, but they showed a marked difference in relative sensitivities. Based on immunoblotting analyses, HCE-1 was present in all tissues examined, whereas HCE-2 and HCE-3 were expressed in a tissue-restricted pattern. Colon carcinomas expressed slightly higher levels of HCE-1 and HCE-2 than the adjacent normal tissues, whereas the opposite was true with HCE-3.

Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
G. Hoffmann, C. Funk, S. Fowler, M. B. Otteneder, A. Breidenbach, C. R. Rayner, T. Chu, and E. P. Prinssen
Nonclinical Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in the Central Nervous System
Antimicrob. Agents Chemother., November 1, 2009; 53(11): 4753 - 4761.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. Lal, J. Sukbuntherng, E. H. L. Tai, S. Upadhyay, F. Yao, M. S. Warren, W. Luo, L. Bu, S. Nguyen, J. Zamora, et al.
Arbaclofen Placarbil, a Novel R-Baclofen Prodrug: Improved Absorption, Distribution, Metabolism, and Elimination Properties Compared with R-Baclofen
J. Pharmacol. Exp. Ther., September 1, 2009; 330(3): 911 - 921.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
A. Watanabe, T. Fukami, M. Nakajima, M. Takamiya, Y. Aoki, and T. Yokoi
Human Arylacetamide Deacetylase Is a Principal Enzyme in Flutamide Hydrolysis
Drug Metab. Dispos., July 1, 2009; 37(7): 1513 - 1520.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S.-R. Kim, K. Sai, T. Tanaka-Kagawa, H. Jinno, S. Ozawa, N. Kaniwa, Y. Saito, A. Akasawa, K. Matsumoto, H. Saito, et al.
Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population
Drug Metab. Dispos., October 1, 2007; 35(10): 1865 - 1872.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. Yang, D. Shi, D. Yang, X. Song, and B. Yan
Interleukin-6 Alters the Cellular Responsiveness to Clopidogrel, Irinotecan, and Oseltamivir by Suppressing the Expression of Carboxylesterases HCE1 and HCE2
Mol. Pharmacol., September 1, 2007; 72(3): 686 - 694.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Tang, M. Mukundan, J. Yang, N. Charpentier, E. L. LeCluyse, C. Black, D. Yang, D. Shi, and B. Yan
Antiplatelet Agents Aspirin and Clopidogrel Are Hydrolyzed by Distinct Carboxylesterases, and Clopidogrel Is Transesterificated in the Presence of Ethyl Alcohol
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1467 - 1476.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. Shi, J. Yang, D. Yang, E. L. LeCluyse, C. Black, L. You, F. Akhlaghi, and B. Yan
Anti-Influenza Prodrug Oseltamivir Is Activated by Carboxylesterase Human Carboxylesterase 1, and the Activation Is Inhibited by Antiplatelet Agent Clopidogrel
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1477 - 1484.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Imai, M. Taketani, M. Shii, M. Hosokawa, and K. Chiba
Substrate Specificity of Carboxylesterase Isozymes and Their Contribution to Hydrolase Activity in Human Liver and Small Intestine
Drug Metab. Dispos., October 1, 2006; 34(10): 1734 - 1741.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. P. Landowski, P. L. Lorenzi, X. Song, and G. L. Amidon
Nucleoside Ester Prodrug Substrate Specificity of Liver Carboxylesterase
J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 572 - 580.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Kubo, S.-R. Kim, K. Sai, Y. Saito, T. Nakajima, K. Matsumoto, H. Saito, K. Shirao, N. Yamamoto, H. Minami, et al.
FUNCTIONAL CHARACTERIZATION OF THREE NATURALLY OCCURRING SINGLE NUCLEOTIDE POLYMORPHISMS IN THE CES2 GENE ENCODING CARBOXYLESTERASE 2 (HCE-2)
Drug Metab. Dispos., October 1, 2005; 33(10): 1482 - 1487.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Imai, M. Imoto, H. Sakamoto, and M. Hashimoto
IDENTIFICATION OF ESTERASES EXPRESSED IN CACO-2 CELLS AND EFFECTS OF THEIR HYDROLYZING ACTIVITY IN PREDICTING HUMAN INTESTINAL ABSORPTION
Drug Metab. Dispos., August 1, 2005; 33(8): 1185 - 1190.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Furihata, M. Hosokawa, N. Koyano, T. Nakamura, T. Satoh, and K. Chiba
IDENTIFICATION OF DI-(2-ETHYLHEXYL) PHTHALATE-INDUCED CARBOXYLESTERASE 1 IN C57BL/6 MOUSE LIVER MICROSOMES: PURIFICATION, CDNA CLONING, AND BACULOVIRUS-MEDIATED EXPRESSION
Drug Metab. Dispos., October 1, 2004; 32(10): 1170 - 1177.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
X. Song, M. Xie, H. Zhang, Y. Li, K. Sachdeva, and B. Yan
THE PREGNANE X RECEPTOR BINDS TO RESPONSE ELEMENTS IN A GENOMIC CONTEXT-DEPENDENT MANNER, AND PXR ACTIVATOR RIFAMPICIN SELECTIVELY ALTERS THE BINDING AMONG TARGET GENES
Drug Metab. Dispos., January 1, 2004; 32(1): 35 - 42.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. P. Sanghani, S. K. Quinney, T. B. Fredenburg, Z. Sun, W. I. Davis, D. J. Murry, O. W. Cummings, D. E. Seitz, and W. F. Bosron
Carboxylesterases Expressed in Human Colon Tumor Tissue and Their Role in CPT-11 Hydrolysis
Clin. Cancer Res., October 15, 2003; 9(13): 4983 - 4991.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. Xie, D. Yang, M. Wu, B. Xue, and B. Yan
Mouse Liver and Kidney Carboxylesterase (M-LK) Rapidly Hydrolyzes Antitumor Prodrug Irinotecan and the N-Terminal Three Quarter Sequence Determines Substrate Selectivity
Drug Metab. Dispos., January 1, 2003; 31(1): 21 - 27.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.