Involvement of human orphan carboxylesterase in drug metabolism and toxicity

2010 Fiscal Year Final Research Report

• 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
• Keywords: 薬物代謝 / 加水分解酵素 / 薬物毒性

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] 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
• [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)
  • Year and Date: 20101127-20101129
• [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)
  • Year and Date: 20101127-20101129
• [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)
  • Year and Date: 20101127-20101129
• [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)
  • Year and Date: 20101007-20101009
• [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)
  • Year and Date: 20101007-20101009
• [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)
  • Year and Date: 20101007-20101009
• [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)
  • Year and Date: 20100904-20100908