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2001 Fiscal Year Final Research Report Summary

Research for the relationship of hereditary sideroblastic anemia with enzyme complex formation in mitochondria

Research Project

Project/Area Number 12670129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

FURUYAMA Kazumichi  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (80280874)

Co-Investigator(Kenkyū-buntansha) HARIGAE Hideo  Tohoku University, University Hospital, Research Associate, 医学部・附属病院, 助手 (50302146)
Project Period (FY) 2000 – 2001
Keywords5-aminolevulinate synthase / Succinyl CoA synthethase / Hereditary Sideroblastic Anemia
Research Abstract

1. To examine whether Erythroid specific 5-aminolevulinate synthase (ALAS-E) and ATP-specific succinyl CoA synthethase (A-SCS) form functional enzyme complex in vitro, we have expressed recombinant proteins of components of each enzyme (ALAS-E, SCS-α, SCS-βA and SCS-βG) using Baclo-virus based expression system. In this experiment, we have successfully purified enzymatically active ALAS-E recombinant protein, however, enzymatic activity of SCS could not be detected in any combination of purified component (SCS-α and SCS-βA = A-SCS, or SCS-α and SCS-βG = G-SCS). These results suggest that phosphorilation or glycosilation SCS might be needed for enzymatically active SCS, which specifically occur in only mammalian cells. Alternatively, mammalian SCS may request specific co-factor(s) for its catalytic activity. If such co-factor(s) exist, decrease amount of the co-factor may cause sideroblastic anemia.
2. To determine the specific region for interaction of ALAS-E and SCS-βA, several deletion mutants of ALAS-E protein were made. Then, the interaction of such mutant ALAS-E proteins and SCS-βA protein were determined using yeast two hybrid system. As a results, 147 amino acid deletion of N-terminal or 50 amino acid deletion of C-terminal of ALAS-E disrupt the interaction of ALAS-E and SCS-βA protein. Since these deletion mutant of ALAS-E results the disruption of homo-dimer formation of ALAS-E, homodimer formation of ALAS-E might be important for enzyme complex formation of ALAS-E and A-SCS in mitochondria.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 古山 和道: "遺伝性鉄芽球性貧血"日本臨床別冊、領域別症候群シリーズ. 33巻. 184-186 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taketani S. 他: "Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemiia K562 cells"European Journal of Biochemistiy. 286巻・6号. 1705-1711 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruno M. 他: "Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD)deficiencies in ALAD porphyria"BLOOD. 97巻・10号. 2972-2978 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sassa S. 他: "Late-onset porphyrias : What are they?"Cellular and Molecular Biology. (発行予定). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuyama K. 他: "Multiple Mechanisms for Hereditary Sideroblastic Anemia"Cellular and Molecular Biology. (発行予定). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 内海耕慥 他監修: "新ミトコンドリア学"共立出版株式会社. 434 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuyama K.: "Hereditary Sideroblastic anemia"Ryoiki-betsu syokogun-sirizu. 33. 184-186 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taketani S., et al: "Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells"European Journal of Biochemistry. 286 (6). 1705-1711 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruno M., et al: "Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria"BLOOD. 97 (10). 2972-2978 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sassa S., et al.: "Late-onset porphyrias : What are they?"Cellular and Molecular Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuyama K., et al.: "Multiple Mechanisms for Hereditary Sideroblastic Anemia"Cellular and Molecular Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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