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1989 Fiscal Year Final Research Report Summary

Molecular biological study on the regulation of fatty acid biosynthesis

Research Project

Project/Area Number 63570126
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TANABE Tadashi  National Cardiovascular Center Research Institute, Department of Parmacology, Director, 薬理部, 部長 (60025624)

Co-Investigator(Kenkyū-buntansha) TAKAI Toshiyuki  Okayama University, Faculty of Engineering Lecturer, 工学部, 講師 (20187917)
YOKOYAMA Chieko  National Cardiovascular Center Research Institute, Department of Parmacology, Re, 薬理部, 室員 (90200914)
IMADA Masaru  Meiji Institute of Health Science, Division of Cell Biology Laboratory Chief
Project Period (FY) 1988 – 1989
KeywordsFatty acid biosynthesis / Metabolic regulation / Acetyl-CoA carboxylase / Biotin / mRNA
Research Abstract

Fatty acids are essential substance for organisms as membrane components, energy sources etc. Accumulation of fatty acids, however, causes various cardiovascular diseases and obesity. In the present study we have investigated the regulatory mechanism of fatty acid biosynthesis to overcome these diseases. According to the previous study by our and other groups, biosynthesis of fatty acid is regulated by modulating the activity of acetyl-CoA carboxylase (ACC). Following results have been obtained by the present study.
1. With use of our cDNA clones of chicken liver ACC as probes and specific antibodies, expression of ACC was studied. ACC mRNA and the enzyme protein was found in liver, brain, testis, kidney, lung and heart. The changes of the hepatic and heart contents of ACC mRNA and the enzyme protein in growing chicks were measured. In the post-hatching period, the bepatic mRNA markedly increased at least 70- fold when compared to that before hatching. This increase was not observed in … More chicks receiving no diet These changes were closely paralleled with the rise of the hepatic content of ACC protein in chicks up to 10 days old. Contents of ACC mRNA and the enzyme protein in heart were not changed during development.
2. Primary structure of various biotin-dependent carboxylase including chicken and rat liver ACC was compared and a genealogical tree was constructed. The results indicated the animal ACC, a multifunctional polypeptide has been formed by gene fusion of monofunctional polypeptide chains found in Escherichia coli ACC during molecular evolution. The result is completely agreed with the previous enzymological observations of biotin-dependent enzymes.
3. Cloning of ACC gene has been attempted by screening human genomic libraries with chicken ACC cDNA as a probe and the obtained colones covered approximately 40 kb of the gene. The 13.4 kb-region of the gene was characterized. The 404 residues of the protein-coding region determined was distributed into 4 exons. The deduced primary structure of human ACC coincided with that of chicken and rat enzymes in 95 and 98 %, respectively. Cloning and characterization of the remaining portion of the gene are now in progress. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 田辺忠: "肝アセチルCoAカルボキシラ-ゼのcDNAクロ-ニングによる構造決定" 脂質生化学研究. 30. 159-162 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高井俊行・斎藤陽子・山本和彦・田辺忠: "Developmental changes of the content of acetyl-CoA carboxylase mRNA in chicken liver" Arch.Biochem.Biophys.266. 313-318 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 和田健司・田辺忠: "Purification and characterization of chicken liver Cathepsin B" J.Biochem.104. 472-476 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田辺忠・横山知永子: "脂肪酸およびプロスタグランジン生合成律速酵素ーAcetyl-CoA CarboxylaseおよびCyclooxygenaseのcDNAクロ-ニングと構造" 循環器病研究の進歩. 10. 60-73 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田辺忠: "AcetylーCoA carboxylaseの構造と活性調節機構" ビタミン. 62. 591-600 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田辺忠・宮田篤郎・横山知永子: "ビオチン酵素の構造と機能" 代謝. 27. 13-19 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tadashi Tanabe: "Determination of the primary structure of liver liver acetyl-CoA carboxylase." Proceedings of Japanese Conference on the Biochemistry of Lipids 30, 159-162, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshiyuki Takai, Yoko Saito, Kazuhiko Yamamoto & Tadashi Tanabe: "Developmental changes of the content of acetyl-CoA carboxylase in chicken liver." Arch. Biochem. Biophys. 266, 313-318, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Wada & Tadashi Tanabe: "Purification and characterization of chicken liver cathepsin B." J. Biochem. 104, 472-476, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tadashi Tanabe & Chieko Yokoyama: "Determination of the primary structure by cDNA cloning of key enzymes of fatty acid and prostaglandin biosynthesi - acetyl-CoA carboxylase and cyclooxygenase." Recent Advances in Cardiovascular Disease 10, 60-63, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tadashi Tanabe: "Primary structure and regulatory mechanism of acetyl-CoA carboxylase." Vitamin (in Japanese) 62, 591-600, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tadashi Tanabe, Atsuro Miyata & Chieko Yokoyama: "Structure and function of biotin-dependent carboxylase." Metabolism (in Japanese) 27, 13-19, 1990.

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Published: 1993-03-26  

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