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Research ArticleArticle

Species Differences in Tissue Distribution and Enzyme Activities of Arylacetamide Deacetylase in Human, Rat, and Mouse

Yuki Kobayashi, Tatsuki Fukami, Akinori Nakajima, Akinobu Watanabe, Miki Nakajima and Tsuyoshi Yokoi
Drug Metabolism and Disposition December 29, 2011, dmd.111.043067; DOI: https://doi.org/10.1124/dmd.111.043067
Yuki Kobayashi
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Tatsuki Fukami
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Akinori Nakajima
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Akinobu Watanabe
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Miki Nakajima
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Tsuyoshi Yokoi
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  • For correspondence: tyokoi@kenroku.kanazawa-u.ac.jp
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Abstract

Human arylacetamide deacetylase (AADAC) is a major esterase responsible for the hydrolysis of clinical drugs such as flutamide, phenacetin, and rifampicin. Thus, AADAC is considered to be a relevant enzyme in preclinical drug development, but there is little information about species differences of AADAC. This study investigated the species differences in the tissue distribution and enzyme activities of AADAC. In human, AADAC mRNA was highly expressed in liver and gastrointestinal tracts, followed by bladder. In rat and mouse, AADAC mRNA was expressed in liver at the highest level, followed by the gastrointestinal tract and kidney. The expression levels in rat tissues were approximately 7- and 10-fold lower than those in human and mouse tissues, respectively. To compare the catalytic efficiency of AADAC between three species, each recombinant AADAC was constructed and their enzyme activities were evaluated by normalizing with the expression levels of AADAC. Flutamide and phenacetin hydrolase activities were detected by the recombinant AADAC of all species. In flutamide hydrolysis, liver microsomes of all species showed similar catalytic efficiencies, despite the lower AADAC mRNA expression in rat liver. In phenacetin hydrolysis, rat liver microsomes showed approximately 4 to 6.5-fold lower activity than human and mouse liver microsomes. High rifampicin hydrolase activity was detected only by recombinant human AADAC and human liver and jejunum microsomes. Collectively, this study clarified the species differences in the tissue distribution and enzyme activities of AADAC. The results of this study facilitate our understanding of the species difference in drug hydrolysis.

  • carboxylesterases
  • enzyme kinetics
  • microsomes
  • Received September 30, 2011.
  • Accepted December 29, 2011.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 51 (6)
Drug Metabolism and Disposition
Vol. 51, Issue 6
1 Jun 2023
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Research ArticleArticle

Species Differences in Tissue Distribution and Enzyme Activities of Arylacetamide Deacetylase in Human, Rat, and Mouse

Yuki Kobayashi, Tatsuki Fukami, Akinori Nakajima, Akinobu Watanabe, Miki Nakajima and Tsuyoshi Yokoi
Drug Metabolism and Disposition December 29, 2011, dmd.111.043067; DOI: https://doi.org/10.1124/dmd.111.043067

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Research ArticleArticle

Species Differences in Tissue Distribution and Enzyme Activities of Arylacetamide Deacetylase in Human, Rat, and Mouse

Yuki Kobayashi, Tatsuki Fukami, Akinori Nakajima, Akinobu Watanabe, Miki Nakajima and Tsuyoshi Yokoi
Drug Metabolism and Disposition December 29, 2011, dmd.111.043067; DOI: https://doi.org/10.1124/dmd.111.043067
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