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Development of an enantioselective amino acid metabolome analysismethod and its clinical applications

Research Project

Project/Area Number 22390007
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionKyushu University

Principal Investigator

HAMASE Kenji  九州大学, 薬学研究院, 准教授 (10284522)

Co-Investigator(Kenkyū-buntansha) KOYANAGI Satoru  九州大学, 大学院・薬学研究院, 准教授 (60330932)
UEDA Tadashi  九州大学, 大学院・薬学研究院, 教授 (90184928)
Co-Investigator(Renkei-kenkyūsha) AISO Sadakazu  慶應義塾大学, 医学部, 教授 (60138013)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywords分析化学 / メタボローム / アミノ酸 / 光学分割
Research Abstract

A highly sensitive and selective 2D-HPLC method for the simultaneous and enantioselective determination of all proteinogenic and clinically used amino acids has been established. The system was applied to various disease model animals and also to human clinical samples. As a result, the amount of D-Ser was higher in the spinal cord of ALS model mouse than that in the control mouse, and the usefulness of chiral amino acid metabolomics was also shown in the metabolic disorders of amino acids. In human plasma and urine, various D-amino acids such as D-Ser and D-Ala were observed, and further studies are in progress

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (58 results)

All 2013 2012 2011 2010 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (37 results) (of which Invited: 2 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Enantioselective two-dimensional high-performance liquid chromatographic determination of N-methyl-D-aspartic acid and its analogues in mammals and bivalves2012

    • Author(s)
      Reiko KOGA, et al.
    • Journal Title

      Journal of Chromatography A

      Volume: 1269 Pages: 255-261

    • DOI

      10.1016/j.chroma.2012.08.075

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of intrinsic amounts of D-serine in tne mice lacking serine racemase and D-amino acid oxidase2012

    • Author(s)
      Yurika MIYOSHI, et al.
    • Journal Title

      Amino Acids

      Volume: 43 Issue: 5 Pages: 1919-1931

    • DOI

      10.1007/s00726-012-1398-4

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Type 1 diabetes mellitus in mice increases hippocampal D-serine in the acute phase after streptozotocin injection.2012

    • Author(s)
      Masataka Suzuki
    • Journal Title

      Brain Res.

      Volume: 1466 Pages: 167-176

    • DOI

      10.1016/j.brainres.2012.05.042

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] D-Amino acid oxidase controls motoneuron degeneration through D-serine2012

    • Author(s)
      Jumpei SASABE, et al
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: 109 Issue: 2 Pages: 627-632

    • DOI

      10.1073/pnas.1114639109

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HPLC analysis of naturally occurring free D-amino acids in mammals2012

    • Author(s)
      Yurika MIYOSHI, et al.
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 69 Pages: 42-49

    • DOI

      10.1016/j.jpba.2012.01.041

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] D-Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity2012

    • Author(s)
      Masahiro YAMANAKA, et al.
    • Journal Title

      Amino Acids

      Volume: 43 Issue: 5 Pages: 1811-1821

    • DOI

      10.1007/s00726-012-1384-x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 哺乳類におけるキラルアミノ酸メタボロミクスを可能とする二次元ミクロHPLC一斉分析法の開発2012

    • Author(s)
      三次百合香、浜瀬健司ほか
    • Journal Title

      BUNSEKI KAGAKU

      Volume: 61 Pages: 489-499

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enantioselective micro-2D-HPLC determination of aspartic acid in the pineal glands of rodents with various melatonin contents2011

    • Author(s)
      Hai HAN, et al
    • Journal Title

      Journal of Separation Science

      Volume: 34 Issue: 20 Pages: 2847-2853

    • DOI

      10.1002/jssc.201100609

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HPLC determination of the distribution of D-amino acids and effects of ecdysis on alanine racemase activity in kuruma prawn Marsupenaeus japonicus2011

    • Author(s)
      Naoko YOSHIKAWA, Waka ASHIDA, KenjiHAMASE, Hiroki ABE
    • Journal Title

      Journal of Chromatography B

      Volume: 879 Issue: 29 Pages: 3283-3288

    • DOI

      10.1016/j.jchromb.2011.04.026

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous determination of D-aspartic acid and D-glutamic acid in rat tissues and physiological fluids using a multi-loop two-dimensional HPLC procedure2011

    • Author(s)
      Hai HAN, et al
    • Journal Title

      Journal of Chromatography B

      Volume: 879 Issue: 29 Pages: 3196-3202

    • DOI

      10.1016/j.jchromb.2011.01.023

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase2011

    • Author(s)
      Yurika MIYOSHI, et al
    • Journal Title

      Journal of Chromatography B

      Volume: 879 Issue: 29 Pages: 3184-3189

    • DOI

      10.1016/j.jchromb.2010.08.024

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] D-Serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor2011

    • Author(s)
      Wataru KAKEGAWA, et al
    • Journal Title

      Nature Neuroscience

      Volume: 14 Issue: 5 Pages: 603-611

    • DOI

      10.1038/nn.2791

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase2011

    • Author(s)
      Y.Miyoshi, K.Hamase, et al.
    • Journal Title

      Journal of Chromatography B

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous determination of D-aspartic acid and D-glutamic acid in rat tissues and physiological fluids using a multi-loop two-dimensional HPLC procedure2011

    • Author(s)
      H.Han, K.Hamase, et al.
    • Journal Title

      Journal of Chromatography B

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] D-Serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor2011

    • Author(s)
      W.Kakegawa, K.Hamase, et al.
    • Journal Title

      Nature Neuroscience

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain2010

    • Author(s)
      Jung Hoon YANG, Akira WADA, Kazuyuki YOSHIDA, Yurika MIYOSHI, Tomoko SAYANO, Kayoko ESAKI, Masami O. KINOSHITA, Shozo TOMONAGA, Norihiro AZUMA, Masahiko WATANABE, Kenji HAMASE, Kiyoshi ZAITSU, Takeo MACHIDA, Albee MESSING, Shigeyoshi ITOHARA, Yoshio HIRAB
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 285 Issue: 53 Pages: 41380-41390

    • DOI

      10.1074/jbc.m110.187443

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chiral amino acid metabolome analysis for biomarker assay in clinical diagnosis using enantioselective 2D-HPLC2013

    • Author(s)
      Kenji HAMASE
    • Organizer
      39th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Amsterdam, The Netherlands
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 二次元 HPLC 分析を基盤とするキラルアミノ酸メタボロミクスの展開2013

    • Author(s)
      浜瀬健司
    • Organizer
      日本薬学会第133 年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] 二次元HPLC分析を基盤とするキラルアミノ酸メタボロミクスの展開2013

    • Author(s)
      浜瀬健司
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 新しい分析法が切り拓く新しい世界‐キラルアミノ酸分析法の開発と創薬・診断の展開‐2012

    • Author(s)
      浜瀬健司
    • Organizer
      第30回九州分析化学若手の会夏季セミナー
    • Place of Presentation
      指宿
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] D- アミノ酸の二次元キラルHPLC 分析を基盤とする創薬・診断の展開2012

    • Author(s)
      浜瀬健司
    • Organizer
      第28回分析化学緑陰セミナー
    • Place of Presentation
      旭川
    • Related Report
      2012 Final Research Report
  • [Presentation] Two-dimensional chiral HPLC analysis of all proteinogenic amino aicds in mammals and its diagnostic value2012

    • Author(s)
      Kenji HAMASE
    • Organizer
      38th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Anaheim, CA, USA
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Development of a sensitive fluorescence HPLC system equipped with an on-line photo reactor for the determination of NBD-tryptophan enantiomers2012

    • Author(s)
      K. Hamase et al.
    • Organizer
      Symposium on Molecular Chirality ASIA 2012
    • Place of Presentation
      Fukuoka,Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] D-アミノ酸の二次元キラルHPLC分析を基盤とする創薬・診断の展開2012

    • Author(s)
      浜瀬健司
    • Organizer
      第28回分析化学緑陰セミナー・旭川
    • Place of Presentation
      旭川
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] アミノ酸分析のニューフロンティア-キラルアミノ酸メタボロミクスの可能性-2011

    • Author(s)
      濱瀬健司
    • Organizer
      新アミノ酸分析研究会第1回学術講演会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Enantioselective micro-2D-HPLC analysis of all proteinogenic aminoacids and its clinical applications2011

    • Author(s)
      K.Hamase, et al
    • Organizer
      37^<th> International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Dalian, China(招待講演)
    • Year and Date
      2011-10-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 哺乳類体内における微量D-アミノ酸の選択的分析法開発と創薬・診断の展開2011

    • Author(s)
      濱瀬健司
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都(招待講演)
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] タンパク質構成全アミノ酸光学異性体の二次元HPLC一斉分析法開発と哺乳類尿中含量の解析2011

    • Author(s)
      濱瀬健司, ほか
    • Organizer
      7回D-アミノ酸研究会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2011-09-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Enantioselective and simultaneous 2D-HPLC determination of all proteinogenic amino acids : a new frontier of the metabolomics study focusing on amino acid enantiomers2011

    • Author(s)
      K.Hamase
    • Organizer
      18^<th> International Symposium on Electro- and Liquid Phase-separation Techniques
    • Place of Presentation
      Tbilisi, Georgia(招待講演)
    • Year and Date
      2011-08-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Selective determination of all D-amino acids in mammalian brain2011

    • Author(s)
      K.Hamase
    • Organizer
      12^<th> International Congress on Amino Acids, Peptides and Proteins
    • Place of Presentation
      Beijing, China
    • Year and Date
      2011-08-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Simultaneous enantioselective analysis of all proteinogenic amino acids in mice lacking enzymes metabolizing D-amino acids2011

    • Author(s)
      K.Hamase, et al
    • Organizer
      36^<th> International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Budapest, Hungary
    • Year and Date
      2011-06-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] キラル識別分析による内在性D-アミノ酸の新たな創薬・診断への可能性探索2011

    • Author(s)
      濱瀬健司
    • Organizer
      第6回トランスポーター研究会年会
    • Place of Presentation
      仙台(招待講演)
    • Year and Date
      2011-06-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 薬学教育の観点からの薬局方改正とクロマトグラフィー2011

    • Author(s)
      濱瀬健司
    • Organizer
      第18回クロマトグラフィーシンポジウム
    • Place of Presentation
      福岡(招待講演)
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Integrated two-dimensional HPLC determination of all proteinogenicamino acid enantiomers and its clinical applications2011

    • Author(s)
      K.Hamase, et al
    • Organizer
      IUPAC International Congress on Analytical Sciences 2011
    • Place of Presentation
      Kyoto, Japan(招待講演)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 光学異性体を区別するタンパク質構成全アミノ酸の二次元HPLC一斉分析法開発と哺乳類内在性含量の解析2011

    • Author(s)
      濱瀬健司, ほか
    • Organizer
      Symposium on Molecular Chirality 2011
    • Place of Presentation
      東京
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] アミノ酸分析のニューフロンティア‐キラルアミノ酸メタボロミクスの可能性‐2011

    • Author(s)
      浜瀬健司
    • Organizer
      新アミノ酸分析研究会第1回学術講演会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] Enantioselective micro-2D-HPLC analysis of all proteinogenic amino acids and its clinical applications2011

    • Author(s)
      Kenji HAMASE
    • Organizer
      37th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Dalian, China
    • Related Report
      2012 Final Research Report
  • [Presentation] 哺乳類体内における微量 D-アミノ酸の選択的分析法開発と創薬・診断の展開2011

    • Author(s)
      浜瀬健司
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] Enantioselective and simultaneous 2D-HPLC determination of all proteinogenic amino acids: a new frontier of the metabolomics study focusing on amino acid enantiomers2011

    • Author(s)
      Kenji HAMASE
    • Organizer
      18th International Symposium on Electroand Liquid Phase-separation Techniques
    • Place of Presentation
      Tbilisi, Georgia
    • Related Report
      2012 Final Research Report
  • [Presentation] Tbilisi, Georgia2011

    • Author(s)
      Kenji HAMASE
    • Organizer
      12th International Congress on Amino Acids, Peptides and Proteins
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Final Research Report
  • [Presentation] Simultaneous enantioselective analysis of all proteinogenic amino acids in mice lacking enzymes metabolizing D- amino acids2011

    • Author(s)
      Kenji HAMASE
    • Organizer
      36th International Symposium on High-Performance Liquid Phase Separations and Related Techniques
    • Place of Presentation
      Budapest, Hungary
    • Related Report
      2012 Final Research Report
  • [Presentation] キラル識別分析による内在性D-アミノ酸の新たな創薬・診断への可能性探索2011

    • Author(s)
      浜瀬健司
    • Organizer
      第6回トランスポーター研究会年会
    • Place of Presentation
      仙台
    • Related Report
      2012 Final Research Report
  • [Presentation] Integrated two-dimensional HPLC determination of all proteinogenic amino acid enantiomers and its clinical applications2011

    • Author(s)
      Kenji HAMASE
    • Organizer
      IUPAC International Congress on Analytical Sciences 2011
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] 高等動物体内における遊離 D-アミノ酸の存在と高感度選択的分析法の開発2011

    • Author(s)
      浜瀬健司
    • Organizer
      生命の起源および進化学会第36回学術講演会
    • Place of Presentation
      福岡
    • Related Report
      2012 Final Research Report
  • [Presentation] 高等動物体内における遊離D-アミノ酸の存在と高感度選択的分析法の開発2011

    • Author(s)
      浜瀬健司
    • Organizer
      生命の起源および進化学会第36回学術講演会
    • Place of Presentation
      福岡
    • Related Report
      2010 Annual Research Report
  • [Presentation] 光学異性体を区別する全アミノ酸二次元 HPLC 一斉分析法の開発と創薬・診断への展開2010

    • Author(s)
      浜瀬健司
    • Organizer
      第23回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      松島
    • Related Report
      2012 Final Research Report
  • [Presentation] Simultaneous enantiomer separations of all proteinogenic amino acids using a fully-automated 2D-HPLC system and the study on accumulation of D-form in the D-amino-acid oxidase deficient animals2010

    • Author(s)
      Kenji HAMASE
    • Organizer
      22nd International Symposium on Chirality
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] 光学異性体を区別するアミノ酸次世代分析装置の開発と医療展開2010

    • Author(s)
      浜瀬健司
    • Organizer
      第47回化学関連支部合同九州大会
    • Place of Presentation
      北九州
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] Two-dimensional HPLC determination of all proteinogenic amino acid enantiomers in mammalian tissues and physiological fluids2010

    • Author(s)
      Kenji HAMASE
    • Organizer
      35th International Symposium on High Performance Liquid Phase Separations & Related Techniques
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] Two-dimensional HPLC determination of all proteinogenic amino acid enantiomers in mammalian tissues and physiological fluids2010

    • Author(s)
      K.Hamase, et al.
    • Organizer
      35^<th> International Symposium on High Performance Liquid Phase Separations & Related Techniques
    • Place of Presentation
      Boston, MA, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Simultaneous enantiomer separations of all proteinogenic amino acids using a fully-automated 2D-HPLC system and the study on accumulation of D-form in the D-amino-acid oxidase deficient animals2010

    • Author(s)
      K.Hamase, et al.
    • Organizer
      22^<nd> International Symposium on Chirality
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2010 Annual Research Report
  • [Presentation] 光学異性体を区別する全アミノ酸二次元HPLC一斉分析法の開発と創薬・診断への展開2010

    • Author(s)
      浜瀬健司
    • Organizer
      第23回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      松島
    • Related Report
      2010 Annual Research Report
  • [Presentation] D-アミノ酸の二次元HPLC精密分析法開発と哺乳類における分布解析2010

    • Author(s)
      浜瀬健司, 他
    • Organizer
      第62回日本生物工学会大会
    • Place of Presentation
      宮崎
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://hyoka.ofc.kyushu-u.ac.jp/search/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 新聞記事(1)ALS 発症 仕組み解明読売新聞2011年12月28日

    • Related Report
      2012 Final Research Report
  • [Remarks] 新聞記事(2)注目は D 型 アミノ酸分析に新兵器読売新聞2010年9月16日

    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 疾患サンプル分析装置、分析システム及び分析方法2012

    • Inventor(s)
      浜瀬健司,東條洋介,三田真史,水本智恵子
    • Industrial Property Rights Holder
      浜瀬健司,東條洋介,三田真史,水本智恵子
    • Industrial Property Number
      2012-061305
    • Filing Date
      2012-03-18
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 分離剤及びその製造方法2012

    • Inventor(s)
      浜瀬健司,三田真史,東條洋介,隅田如光
    • Industrial Property Rights Holder
      浜瀬健司,三田真史,東條洋介,隅田如光
    • Industrial Property Number
      2012-018838
    • Filing Date
      2012-01-31
    • Related Report
      2012 Final Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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