Involvement of human orphan carboxylesterase in drug metabolism and toxicity

• Project/Area Number: 21790148
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: FUKAMI Tatsuki Kanazawa University, 薬学系, 助教 (00532300)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 薬物代謝 / 加水分解酵素 / 薬物毒性 / 加水分解 / 薬物誘発性肝障害

Research Abstract

This study demonstrated that human arylacetamide deacetylase (AADAC) catalyzes the hydrolysis of flutamide, phenacetin, and rifamycins, which are reported to be associated with toxicity. In addition, it was found that the expression level of AADAC mRNA was decreased by bile acid through the repression of HNF4a activity by FXR-induced SHP.

Research Products

• [Journal Article] Arylacetamide deacetylase is a determinant enzy e for the difference in hydrolase activities of phenacetin and acetaminophen. (2010)
  • Author(s): Watanabe, A., Fukami, T., Takahashi, S., Kobayashi, Y., Nakagawa, N., Nakajima, M., Yokoi, T.
  • Journal Title: 38 Pages: 1532-1537
  • Peer Reviewed
• [Journal Article] In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities. (2010)
  • Author(s): Fukami, T., Takahashi, S., Nakagawa, N., Maruichi, T., Nakajima, M., Yokoi, T.
  • Journal Title: 38 Pages: 2173-2178
  • Peer Reviewed
• [Journal Article] Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen. (2010)
  • Author(s): Akinobu Watanabe, Tatsuki Fukami, Shiori Takahashi, Yuki Kobayashi, Nao Nakagawa, Miki Nakajima, Tsuyoshi Yokoi
  • Journal Title: Drug Metabolism and Disposition Volume: 38(9) Pages: 1532-1537
  • Peer Reviewed
• [Journal Article] In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities. (2010)
  • Author(s): Tatsuki Fukami, Shiori Takahashi, Nao Nakagawa, Taiga Maruichi, Miki Nakajima, Tsuyoshi Yokoi
  • Journal Title: Drug Metabolism and Disposition Volume: 38(12) Pages: 2173-2178
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of human carboxylesterase 1Al by nuclear factor-erythroid 2 related factor 2 (Nrf2). (2010)
  • Author(s): Taiga Maruichi, Tatsuki Fukami, Miki Nakajima, Tsuyoshi Yokoi
  • Journal Title: Biochemical Pharmacology 79・2 Pages: 288-295
  • Peer Reviewed
• [Journal Article] Human arylacetamide deacetylase is a principle enzyme in flutamide hydrolysis. (2009)
  • Author(s): Watanabe, A., Fukami, T., Nakajima, M., Takamiya, M., Aoki, Y., Yokoi, T.
  • Journal Title: 37 Pages: 1513-1520
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of human carboxylesterase 1A1 by nuclear factor-erythroid 2 related factor 2 (Nrf2) (2009)
  • Author(s): Maruichi, T., Fukami, T., Nakajima, M., Yokoi, T.
  • Journal Title: 79 Pages: 288-295
  • Peer Reviewed
• [Journal Article] Human arylacetamide deacetylase is a principal enzyme in flutamide hydrolysis. (2009)
  • Author(s): Akinobu Watanabe, Tatsuki Fukami, Miki Nakajima, Masataka takamiya, Yasuhiro Aoki, Tsuyoshi Yokoi
  • Journal Title: Drug Metabolism and Disposition 37・7 Pages: 1513-1520
  • NAID: 130004639493
  • Peer Reviewed
• [Presentation] ヒトアリルアセタミドデアセチラーゼのフルタミド加水分解に対する関与 (2010)
  • Author(s): 渡邊旭延, 深見達基, 中島美紀, 高宮正隆, 青木康博, 横井毅
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] ヒトカルボキシルエステラーゼ1AのNrf2による転写調節 (2010)
  • Author(s): 丸一泰雅, 深見達基, 中島美紀, 横井毅
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] 糖尿病および高脂血漿治療薬のヒトカルボキシルエステラーゼ酵素活性に対する阻害効果 (2010)
  • Author(s): 深見達基, 高橋志織, 中川尚, 中島美紀, 横井毅
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] フェナセチンおよびアセトアミノフェンによる毒性の差異に対するヒトアリルアセタミドデアセチラーゼの重要性 (2010)
  • Author(s): 深見達基, 渡邊旭延, 高橋志織, 小林祐喜, 中川尚, 中島美紀, 横井毅
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] ヒトアリルアセタミドデアセチラーゼはリファマイシン系薬物の加水分解を担う主代謝酵素である (2010)
  • Author(s): 中島彰紀, 深見達基, 渡邊旭延, 小林祐喜, 中島美紀, 横井毅
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] マウス、ラット及びヒトにおけるアリルアセタミドデアセチラーゼの発現臓器及び酵素活性の種差に関する検討 (2010)
  • Author(s): 小林祐喜, 深見達基, 中島彰紀, 渡邊旭延, 中島美紀, 横井毅
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen. (2010)
  • Author(s): Fukami.T, Watanabe.A, Takahashi.S, Nakagawa.N, Nakajima.M, Yokoi.T.
  • Organizer: 9^<th> International ISSX Meeting
  • Place of Presentation: Istanbul Convention and Exhibition Centre (Turkey)
• [Presentation] Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen. (2010)
  • Author(s): Tatsuki Fukami, Akinobu Watanabe, Shiori Takahashi, Nao Nakagawa, Miki Nakajima, Tsuyoshi Yokoi
  • Organizer: 9th International ISSX Meeting
  • Place of Presentation: CONGRESS CENTER (Turkey)
• [Presentation] フェナセチンおよびアセトアミノフェンによる毒性の差異に対するヒトアリルアセタミドデアセチラーゼの重要性 (2010)
  • Author(s): 深見達基、渡邊旭延、高橋志織、小林祐喜、中川尚、中島美紀、横井毅
  • Organizer: 日本薬物動態学会 第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] ヒトアリルアセタミドデアセチラーゼはリファマイシン系薬物の加水分解を担う主代謝酵素である (2010)
  • Author(s): 中島彰紀、深見達基、渡邊旭廷、小林祐喜、中島美紀、横井毅
  • Organizer: 日本薬物動態学会 第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] マウス、ラット及びヒトにおけるアリルアセタミドデアセチラーゼの発現臓器及び酵素活性の種差に関する検討 (2010)
  • Author(s): 小林祐喜、深見達基、中島彰紀、渡邊旭延、中島美紀、横井毅
  • Organizer: 日本薬物動態学会 第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉県)
• [Presentation] ヒトアリルアセタミドデアセチラーゼのフルタミド加水分解に対する関与 (2009)
  • Author(s): 渡邊旭延、深見達基、中島美紀、高宮正隆、青木康博、横井毅
  • Organizer: 第24回日本薬物動態学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] ヒトカルボキシルエステラーゼ1AのNrf2による転写調節 (2009)
  • Author(s): 丸一泰雅、深見達基、中島美紀、横井毅
  • Organizer: 第24回日本薬物動態学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] 糖尿病および高脂血漿治療薬のヒトカルボキシルエステラーゼ酵素活性に対する阻害効果 (2009)
  • Author(s): 深見達基、高橋志織、中川尚、中島美紀、横井毅
  • Organizer: 第24回日本薬物動態学会年会
  • Place of Presentation: 国立京都国際会館(京都府)