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Research for the Inhibitor of Cholesterol Biosynthesis with the aid of Morus alba Callus Cultures

Research Project

Project/Area Number 06672116
Research Category

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

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionToho University

Principal Investigator

NOMURA Taro  Toho University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90057505)

Co-Investigator(Kenkyū-buntansha) HANO Yoshio  Toho University, Faculty of Pharmaceutical Sciences, associate, prof., 薬学部, 助教授 (00156382)
上田 伸一  京都大学, 薬学部, 助教授 (20025688)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsMorus alba Callus Cultures / Isoprenoid Biosynthesis / HMG CoA reductase / Compactin / beta-Sitosterol / Isoprenylated phenol / Cholesterol / Hypercholesteremia / イソプレノイド生合成 / Morus alba / カルス / メバロン酸 / 生合成 / HMG-COA還元酵素阻害剤
Research Abstract

Morus alba Cell cultures have at least two isoprenoid biosynthetic pathways, one of which is that for isoprenylated phenols and the other is that for sterols. In the administration of experiment with compactin, a potential 3-hydroxy 3-methylglutaryl CoA (HMG CoA) reductase inhibitor, to the M.alba cell cultures, the biosynthesis of the isoprene unit of the isoprenylated phenol was not affected by compactin, while the biosynthesis of the isoprene unit of beta-sitosterol from acetate was inhibited. This result suggests that compactin is a specific inhibitor of sterol biosynthesis from acetate origin. This work thus indicates the occurrence of at least two isoprenoid biosynthetic pathways, one of which is susceptible to compactin and the other resistant to compactin in M.alba cell cultures. In the previous experiment with [2-^<13>C] acetate, it has been found that the tricarboxylic acid (TCA) cycle participates in the biosynthesis of the isoprene unit of the isoprenylated phenol in M.alba cell cultures. In the administration of [2-^<13>C] acetic acid N-acetylcysteamine thioester to the cell cultures, the acetate precursor was intact into the isoprene unit of the isoprenylated phenol without the participation of the TCA cycle.
On the other hand, the isoprenylated phenols in the cell cultures are biosynthesized from cinnamoylpolyketide intermediate. Simultaneous administration of ^<13>C-labeled L-phenylalanine and L-tyrosine as well as administration of ^<13>-labeled cinnamic acid N-acetylcysteamine thioester derivative to the M.alba cell cultures gave a conclusive evidence for the two independent pathways leading to p-coumaroyl CoA.One is pathway from L-phenylalanine to p-coumaroyl CoA by way of cinnamoyl CoA and the other is pathway from L-tyrosine to p-coumaroyl CoA through the deamination reaction.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Yoshio Hano: "Direct NMR Evidence for the Equivalent Participation of L-Phenylalanine and L-Tyrosin in the Biosynthesis of the Intermolecular Diels-Alder Type Adducts of Prenylchalcone and Prenylated 2-Arylbenzofuran in Morus alba Cell Cultures" Canadian J.Chemistry. 72. 12-14 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taro Nomura: "Isoprenoid-substituted Phenolic Compounds of Moraceous Plants" Natural Product Reports. 11. 205-218 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Origin of the Acetate Units Composing the Hemiterpene Moieties of Chalcomoracin in Morus alba Cell Cultures" J.Am.Chem.Soc.116. 4189-4193 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Parallel Contribution of L-Phenylalanine and L-Tyrosine to Biosynthesis of Prenylchalcones in Morus alba Cell Cultures" Naturwissenschaften. 81. 507-509 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Alternative Response of Two Isoprenoid Biosynthetic Pathways to Compactin in Morus alba Cell Cultures" Naturwissenschaften. 82. 376-378 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taro Nomura: "Chemistry and Biosynthesis of Natural Diels-Alder Type Adducts from Moraceous Plants" Studies in Natural Products Chemistry. 17. 451-478 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Direct NMR Evidence for the Equivalent Participation of L-Phenylalanine and L-Tyrosin in the Biosynthesis of the Intermolecular Diels-Alder Type Adducts of Prenylchanlcone and Prenylated 2-Arylbenzofuran in Morus alba Cell Cultures" Canadian J.Chemistry. 72. 12-14 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taro Nomura: "Isoprenoid-substituted Phenolic Compounds of Moraceous Plants" Natural Product Reports. 11. 205-218 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Original of the Acetate Units Composing the Hemiterpene Moieties of Chalcomoracin in Morus alba Cell Cultures" J.Am.Chem.Soc.116. 4189-4193 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Parallel Contribution of L-Phenylalanine and L-Tyrosine to Biosynthesis of Prenylchalcones in Morus alba Cell Cultures" Naturwissenschaften. 81. 507-509 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Alternative Response of Two Isoprenoid Biosynthetic Pathways to Compactin in Morus alba Cell Cultures" Naturwissenschaften. 82. 376-378 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taro Nomura: "Chemistry and Biosynthesis of Natural Diels-Alder Type Adducts from Moraceous Plants" Studies in Natural Products Chemistry. 17. 451-478 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio Hano: "Direct NMR Evidence for the Equivalent Participation of L-Phenylalanine and L-Tyrosine in the Biosynthesis of the Intermolecular Diels-Alder Type Adducts of Prenylchalcone and Prenylated 2-Arylbenzofuran in Morus alba Cell Cultures" Canadian J. Chemistry. 72. 12-14 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taro Nomura: "Isoprenoid-substituted Phenolic Compounds of Moraceous Plants" Natural Product Reports. 11. 205-218 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshio Hano: "Origin of the Acetate Units Composing the Hemiterpene Moieties of chalcomoracin in Morus alba Cell Cultures" J. Am. Chem. Soc.116. 4189-4193 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshio Hano: "Parallell Contribution of L-Phenylalanine and L-Tyrosine to Biosynthesis of Prenylchalcone in Morus alba Cell Cultures" Naturwissenschaften. 81. 507-509 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshio Hano: "Alternative Response of Two Isoprenoid Biosynthetic Pathways to Compactin in Morus alba Cell Cultures" Naturwissenschaften. 82. 376-378 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taro Nomura: "Chemistry and Biosynthesis of Natural Diels-Alder Type Adducts from Moraceous Plants" Studies in Natural Products Chemistry. 17. 451-478 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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