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Regulation properties of glycolytic pathway in Toxoplasma gondii (enzyme property investigation)

Research Project

Project/Area Number 17590376
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionKeio University

Principal Investigator

TAKASHI Asai  Keio University, School of Medicine, Assistant Professor (50175163)

Co-Investigator(Kenkyū-buntansha) MAEDA Takuya  The University of Tokyo, The Institute of Medical Science, Research Associate (20383763)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,280,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsGlycolytic Pathway / Hexokinase / Pyruvate Kinase / Phosphoglucomutase / Parasitic Protozoa / Toxoplasma gondii / Mitochondria / Apicoplast / 寄生虫 / 遺伝子組換酵素 / グルコース6-リン酸 / 系統樹解析
Research Abstract

A regulation mechanism of glycolytic pathway in Toxoplasma gondii is very simple. The initial product, glucose 6-phosphate, acts on an allosteric activator for pyruvate kinase and determines the flow rate. Other tentative key enzymes, hexokinase and phosphofructokinase, have no regulation properties. This is very surprising event because host organisms like human have very complicated some regulation mechanisms. In the process of this research, we have identified a novel pyruvate kinase whose physiological role is unknown. This enzyme use GDP as a substitute far ADP for the enzyme reaction. The pH optimal of this enzyme is in higher position and the enzyme is present in the mitochondrion and the apicoplast. There are no organisms except Toxoplasma gondii have the pyruvate kinase in mitochondrion up to date. A participation of this enzyme to the glycolytic pathway of Toxoplasma gondii is still unknown. The presence of this enzyme in the mitochondrion and the apicoplast has been extensively studied by using the some deletion mutants of N-terminal of this enzyme (J. Biol. Chem. in press). The physiological function of this enzyme is a future project to be solved. From the fact that glucose 6-phosphate is the most important substance for the glycolitic pathway of Toxoplasma gondii, we have made a recombinant protein for phosphoglucomutase that use glucose 6-phosphate as a substrate, and investigated some properties of phosphoglucomutase. Amino acid alignment analysis indicated that Toxoplasma gondii phosphoglucomutase was closely related to plant enzymes, and faraway to bacteria enzymes and closely related species, Plasmodium enzymes. There are no conspicuous properties in Toxoplasma gondii phosphoglucomutase but sensitiveness for the bivalent cation is quite different to other organism enzymes. We will report the properties of phosphoglucomutase in Toxoplasma gondii in the near future.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2008 2007 2006 2005

All Journal Article (7 results) (of which Peer Reviewed: 3 results) Presentation (11 results) Book (3 results)

  • [Journal Article] A NOVEL GDP-DEPENDENT PYRUVATE KINASE ISOZYME FROM Toxoplasma gondii LOCALIZES TO BOTH THE APICOPLAST AND THE MITOCHONDRION2008

    • Author(s)
      Saito T, Nishi M, Lim MI, Wu B, Maeda T, Hashimoto H, Takeuchi T, Roos DS and Asai T
    • Journal Title

      J.Biol.Chem. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A NOVEL GDP-DEPENDENT PYRUVATE KINASE ISOZYME FROM Toxoplasma gondii, LOCALIZES TO BOTH THE APICOPLAST AND THE MITOCHONDRION2008

    • Author(s)
      Tomoya, Saito, Manami, Nishi, Muoy, I., Lim, Bo, Wu, Takuya, Maeda, Hisayuki, Hashimoto, Tsutomu, Takeuchi, David, S., Roos, Takashi, Asai
    • Journal Title

      J. Biol. Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] ANOVEL GDP-DEPENDENT PYRiTVATE KINASE ISOZYME FROM Toxoplasma gondii LOCALIZES TO BOTH THE APICOPLAST AND THEMITOCHONDRION2008

    • Author(s)
      Saito T, Nishi M, Lim MI, Wu B, Maeda T, Hashimoto H, Takeuchi T, Roos DS, Asai T
    • Journal Title

      J.Biol.Chem

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biochemistry and Metabolism of Toxoplasma gondii2006

    • Author(s)
      Asai, T, Tomavo, S
    • Journal Title

      Toxoplasma gondii. The Model Apicomplexan-Perspective and Method Weiss and Kim eds, Academic Press

      Pages: 185-206

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] トキソプラズマ髄膜脳炎と診断における18S rDNAを標的とするnested-PCR法の評価2005

    • Author(s)
      前田 卓哉, 斉藤 智也、竹内 勤、浅井 隆志
    • Journal Title

      感染症学雑誌 79

      Pages: 543-548

    • NAID

      40006834009

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of a Nested-PCR to Detect 18S rDNA for the Diagnosis of Toxoplasmic Meningoencephalitis2005

    • Author(s)
      Takuya, Maeda, Tomoya, Saito, Tsutomu, Takeuchi, Takashi, Asai
    • Journal Title

      The Journal of the Japanese Association for Infectious Diseases 79

      Pages: 543-548

    • NAID

      130004112867

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] トキソプラズマ髄膜脳炎と診断における18S rDNAを標的とするnested-PCR法の評価2005

    • Author(s)
      前田卓哉, 斉藤智也, 竹内勤, 浅井隆志
    • Journal Title

      感染症学雑誌 79

      Pages: 543-548

    • NAID

      40006834009

    • Related Report
      2005 Annual Research Report
  • [Presentation] トキソプラズマ感染マウスにおけるNTPase阻害剤{2-(1-Naphthalenylthio)1-H-indol}の投与効果2007

    • Author(s)
      浅井 隆志、David Sibley、竹内 勤
    • Organizer
      第76回日本寄生虫学会大会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] トキソプラズマ原虫のGDP依存型ピルビン酸キナーゼ・アイソザイム(TgPykII)のミトコンドリアとアピコプラストにおける共局在の確認2007

    • Author(s)
      斉藤 智也、西真 奈美、Muoy I.Rim、竹内 勤、David S.Roos、浅井 隆志
    • Organizer
      第6回分子寄生虫、マラリア研究フォーラム
    • Place of Presentation
      松山
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effect of medication of NTPase inhibiter, {2-(1-Naphthalenylthio)1 H indol}, on mice infected with Toxoplasma gondii2007

    • Author(s)
      Asai, T, Sibley, D, Takeuchi, T
    • Organizer
      The 76th Japanese Parasitology Meeting
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A confirmation of GDP-dependent pyruvate kinase isozyme(TgPykII)in its presentation at the mitochondrion and the apicoplast of Toxoplasma gondii2007

    • Author(s)
      Saito, T, Nishi, M, Rim, MI, Takeuchi, T, Roos, DS, Asai, T
    • Organizer
      The 6th Molecular Parasitology and Malarial
    • Place of Presentation
      Matsuyama
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] トキソプラズマ原虫のGDP依存型ピルビン酸キナーゼ・アイソザイム(TgPykII)のミトコンドリアとアピコプラストにおける共局在の確認2007

    • Author(s)
      斉藤 智也、西真 奈美、Muoy I. Rim、竹内 勤、David S. Roos、浅井 隆志
    • Organizer
      第6回分子寄生虫・マラリア研究フォーラム
    • Place of Presentation
      松山
    • Related Report
      2007 Annual Research Report
  • [Presentation] トキソプラズマと熱帯熱マラリア原虫に見出された解糖経路上に位置しない新規のピルビン酸キナーゼ反応酵素2006

    • Author(s)
      斉藤 智也、前田 卓哉、竹内 勤、浅井 隆志
    • Organizer
      第75回日本寄生虫学会大会
    • Place of Presentation
      弘前
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] トキソプラズマの糖代謝調節機構2006

    • Author(s)
      浅井 隆志、斉藤 智也、前田 卓哉、竹内 勤
    • Organizer
      第5回分子寄生虫、マラリア研究フォーラム
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A reaction mechanism of the non-glycolytic pyruvate kinases found in Toxoplasma gondii and Plasmodium falciparum2006

    • Author(s)
      Saito, T, Maeda, T, Takeuchi, T, Asai, T
    • Organizer
      The 75 th Japanese Parasitology Meeting
    • Place of Presentation
      Hirosaki
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A regulation mechanism of glycolytic pathway of Toxoplasma gondii2006

    • Author(s)
      Asai, T, Saito, T, Maeda, T, Takeuchi, T
    • Organizer
      The 5th Molecular Parasitology and Malarial Forum
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A Novel GDP-dependent pyruvate kinase isozyme from Toxoplasma gondli is targeted to both the mitochondrion and the apicoplast2005

    • Author(s)
      Saito T, Maeda T, Nishi M, Roos DS, Takeuchi T, Asai T
    • Organizer
      XIIth International Congress on Toxoplasmosis
    • Place of Presentation
      France(Corsica)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A novel GDP-dependent pyruvate kinase isozyme from Toxoplasma gondii is targeted to both the mitochondrion and the apicoplast2005

    • Author(s)
      Saito, T, Maeda, T, Nishi, M, Roos, DS, Takeuchi, T, Asai, T
    • Organizer
      XIIth International Congress on Toxoplasmosis
    • Place of Presentation
      France
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Toxoplasma gondii (Biochemistry and Metabolism of Toxoplasma gondil)2006

    • Author(s)
      Asai T and Tomavo S
    • Publisher
      Academic Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Toxoplasma gondii : The Model Apicomplexan-Perspective and Methods, Chapter : Biochemisrry and Metabolism2006

    • Author(s)
      Asai T, Tomavo S(Weiss, Kim Eds)
    • Publisher
      Elsevier Science
    • Related Report
      2006 Annual Research Report
  • [Book] Toxoplasma gondii : The Model Apicomplexan- Perspective and Methods2006

    • Author(s)
      Asai T., Tomavo S., (Weiss Eds)
    • Publisher
      Elsevier Science (In press)
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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