Analysis of the lysosomal enzyme metabolizing the anti-inflammatory lipid, N-acylethanolamine

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790295
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kagawa University
• Principal Investigator: TSUBOI Kazuhito 香川大学, 医学部, 助教 (80346642)
• Project Period (FY): 2010 – 2011
• Keywords: 脂質 / 酵素 / 生理活性 / 生体分子

Research Abstract

In the present study, we analyzed enzymes metabolizing the anti-inflammatory lipid, N-acylethanolamine(NAE). We found that NAE-hydrolyzing acid amidase(NAAA), a lysosomal enzyme degrading NAEs, is activated by endogenous substances such as some phospholipids and dihydrolipoic acid and that several lipophilic amines are new inhibitors of NAAA. Furthermore, we suggested that HRASLS1, a member of the tumor suppressor HRASLS family, is involved in NAE biosynthesis by its N-acyltransferase activity.

Research Products

• [Journal Article] Regulation of peroxisomal lipid metabolism by catalytic activity of tumor suppressor H-rev107 (2012)
  • Author(s): Uyama, T., Ichi, I., Kono, N. Inoue, A., Tsuboi, K., Jin, X.-H., Araki, N., Aoki, J., Arai, H., and Ueda, N
  • Journal Title: Journal of Biological Chemistry Volume: 287 Pages: 2706-2718
  • Peer Reviewed
• [Journal Article] Endogenous molecules stimulating N-acylethanolamine-hydrolyzing acid amidase(NAAA) (2012)
  • Author(s): Tai, T., Tsuboi, K., Uyama, T., Masuda, K., Cravatt, B. F., Houchi, H., and Ueda, N
  • Journal Title: ACS Chemical Neuroscience
  • DOI: DOI:10.1021/cn300007s
  • Peer Reviewed
• [Journal Article] Lipophilic amines as potent inhibitors of N-acylethanolamine-hydrolyzing acid amidase (2012)
  • Author(s): Yamano, Y., Tsuboi, K., Hozaki, Y., Takahashi, K., Jin, X.-H., Ueda, N., and Wada, A
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 20 Pages: 3658-3665
  • Peer Reviewed
• [Journal Article] Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol (2011)
  • Author(s): Ueda, N., Tsuboi, K., Uyama, T., and Ohnishi, T
  • Journal Title: BioFactors Volume: 37 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Studies on the anorectic effect of N-acylphosphatidylethanolamine and phosphatidylethanolamine in mice (2011)
  • Author(s): Wellner, N., Tsuboi, K., Madsen, A. N., Holst, B., Diep, T. A., Nakao, M., Tokumura, A., Burns, M. P., Deutsch, D. G., Ueda, N., and Hansen, H. S
  • Journal Title: Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids Volume: 1811 Pages: 508-512
  • Peer Reviewed
• [Journal Article] Enzymatic formation of N-acylethanol-amines from N-acylethanolamine plasmalogen through N-acylphosphati-dylethanol-amine-hydrolyzing phos-pholipase D-dependent and-independent pathways (2011)
  • Author(s): Tsuboi, K., Okamoto, Y., Ikematsu, N., Inoue, M., Shimizu, Y., Uyama, T., Wang, J., Deutsch, D. G., Burns, M. P., Ulloa, N. M., Tokumura, A., and Ueda, N
  • Journal Title: Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids Volume: 1811 Pages: 565-577
  • Peer Reviewed
• [Journal Article] Enzymological analysis of the tumor suppressor A-C1 reveals a novel group of phospholipid-metabolizing enzymes (2011)
  • Author(s): Shinohara, N., Uyama, T., Jin, X.-H., Tsuboi, K., Tonai, T., Houchi, H., and Ueda, N
  • Journal Title: Journal of Lipid Research Volume: 52 Pages: 1927-1935
  • Peer Reviewed
• [Journal Article] 三本鎖のリン脂質N-アシルホスファチジルエタノールアミンの動物組織における代謝 (2011)
  • Author(s): 坪井一人, 宇山徹, 上田夏生
  • Journal Title: 生化学 Volume: 83 Pages: 485-494
  • Peer Reviewed
• [Journal Article] 脂質メテ〓メィエーターとして機能するN-アシルエタノールアミンの分解酵素とその阻害薬 (2011)
  • Author(s): 坪井一人, 上田夏生
  • Journal Title: 日本薬理学雑誌 Volume: 138 Pages: 8-12
• [Journal Article] 食欲抑制メディエーターとしてのオレオイルエタノールアミド (2011)
  • Author(s): 上田夏生, 坪井一人, 宇山徹
  • Journal Title: ビタミン Volume: 85 Pages: 604-607
• [Journal Article] N-acylethanolamine metabolism with special reference to N-acylethanol-amine-hydrolyzing acid amidase(NAAA) (2010)
  • Author(s): Ueda, N., Tsuboi, K., and Uyama, T
  • Journal Title: Progress in Lipid Research Volume: 49 Pages: 299-315
  • Peer Reviewed
• [Journal Article] Enzymological studies on the biosynthesis of N-acylethanolamines (2010)
  • Author(s): Ueda, N., Tsuboi, K., and Uyama, T
  • Journal Title: Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids Volume: 1801 Pages: 1274-1285
  • Peer Reviewed
• [Presentation] マウス全脳におけるエタノールアミン含有脂質の分子種分析と関連酵素の基質特異性解析 (2011)
  • Author(s): 池松夏紀, 坪井一人, 井上愛美, 清水嘉文, 宇山徹, 田中保, 上田夏生, 徳村彰
  • Organizer: 第50回日本薬学会日本薬剤師会日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 香川
  • Year and Date: 2011-11-13
• [Presentation] がん抑制遺伝子群HRASLSファミリーはリン脂質代謝酵素として機能する (2011)
  • Author(s): 篠原尚樹, 宇山徹, 坪井一人, 芳地一, 上田夏生
  • Organizer: 第50回日本薬学会日本薬剤師会日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 香川
  • Year and Date: 2011-11-13
• [Presentation] レシチン・レチノール・アシルトランスフェラーゼにホモロジーを示すがん抑制遺伝子HRASLSファミリー・メンバーのリン脂質代謝酵素活性 (2011)
  • Author(s): 上田夏生, 宇山徹, 金星華, 坪井一人, 芳地一, 藤内武春
  • Organizer: 第332回脂溶性ビタミン総合研究委員会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-30
• [Presentation] N-アシル化プラズマローゲンリン脂質からのN-アシルエタノールアミンの生合成 (2011)
  • Author(s): 坪井一人, 岡本安雄, 池松夏紀, 井上愛美, 清水嘉文, 宇山徹, Dale G. Deutsch, 徳村彰, 上田夏生
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] Phospholipase A/ Acyltransferase(PLA/ AT)ファミリーの細胞内におけるN-アシルホスファチジルエタノールアミン生合成への関与 (2011)
  • Author(s): 宇山徹, 池松夏紀, 井上愛美, 篠原尚樹, 金星華, 坪井一人, 藤内武春, 徳村彰, 上田夏生
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] The tumor suppressor A-C1 has an N-acyltransferase activity involved in NAPE formation (2011)
  • Author(s): Shinohara, N., Uyama, T., Jin, X.-H., Tsuboi, K., Tonai, T., Houchi, H., and Ueda, N
  • Organizer: 21st Annual symposium of the International Cannabinoid Research Society
  • Place of Presentation: St. Charles, IL, USA
  • Year and Date: 2011-07-06
• [Presentation] LRATに相同性を示す癌抑制遺伝子群HRASLSファミリーの脂質代謝酵素活性 (2011)
  • Author(s): 宇山徹, 篠原尚樹, 金星華, 坪井一人, 藤内武春, 芳地一, 上田夏生
  • Organizer: 日本ビタミン学会第63回大会
  • Place of Presentation: 広島
  • Year and Date: 2011-06-04
• [Presentation] 癌抑制遺伝子群HRASLSファミリー・メンバーHRASLS1のリン脂質代謝酵素活性 (2011)
  • Author(s): 宇山徹, 篠原尚樹, 金星華, 坪井一人, 藤内武春, 芳地一, 上田夏生
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-12
• [Presentation] LRATファミリーに属するヒト新規脂質代謝酵素群の機能解析 (2011)
  • Author(s): 宇山徹, 篠原尚樹, 金星華, 坪井一人, 藤内武春, 芳地一, 上田夏生
  • Organizer: 日本農芸化学会中四国支部第29回講演会日本ビタミン学会中国・四国地区第1回講演会合同講演会
  • Place of Presentation: 徳島
  • Year and Date: 2011-01-22
• [Presentation] 癌抑制遺伝子群HRASLSファミリー・メンバーA-C1の脂質代謝酵素としての解析 (2010)
  • Author(s): 篠原尚樹, 宇山徹, 金星華, 坪井一人, 藤内武春, 芳地一, 上田夏生
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 兵庫
  • Year and Date: 2010-12-09
• [Presentation] Human tumor suppressors have a NAPE-forming N-acyltransferase activity (2010)
  • Author(s): Uyama, T., Jin, X.-H., Shinohara, N., Tsuboi, K., Tonai, T., and Ueda, N
  • Organizer: 20th Annual symposium of the International Cannabinoid Research Society
  • Place of Presentation: Lund, Sweden
  • Year and Date: 2010-07-25
• [Presentation] ヒト癌抑制遺伝子HRASLSファミリーの脂質代謝酵素活性の解析 (2010)
  • Author(s): 宇山徹, 金星華, 篠原尚樹, 坪井一人, 上田夏生
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-06-14
• [Presentation] LRATファミリーに属する4種のヒト新規脂質代謝酵素の機能解析 (2010)
  • Author(s): 宇山徹, 金星華, 篠原尚樹, 坪井一人, 藤内武春, 上田夏生
  • Organizer: 日本ビタミン学会第62回大会
  • Place of Presentation: 岩手
  • Year and Date: 2010-06-12
• [Presentation] Identification of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes (2010)
  • Author(s): Uyama, T., Jin, X.-H., Shinohara, N., Tsuboi, K., and Ueda, N
  • Organizer: Keystone Symposia : Bioactive Lipids : Biochemistry and Diseases
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-06-09
• [Presentation] ヒト癌抑制遺伝子HRASLSファミリーのリン脂質代謝酵素としての同定 (2010)
  • Author(s): 宇山徹, 金星華, 篠原尚樹, 坪井一人, 上田夏生
  • Organizer: 第51回日本生化学会中国・四国支部例会
  • Place of Presentation: 山口
  • Year and Date: 2010-05-15
• [Remarks] ホームページ
  • URL: http://www.kms.ac.jp/~biochem/index.html