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Menaquinone-4, a potent anti-osteoporosis vitamin : Clarification of its intracellular distribution and new physiological function

Research Project

Project/Area Number 09660127
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 食品科学・栄養科学
Research InstitutionTohoku University

Principal Investigator

KOMAI Michio  Tohoku University Department of Science of Biological Function, Division of Life Science, Graduate School of Agricultural Science, Associate Professor, 農学部, 助教授 (80143022)

Co-Investigator(Kenkyū-buntansha) ITO Michiko  Tohoku University Department of Science of Biological Function, Division of Life, 農学部, 教務職員 (60250734)
FURUKAWA Yuji  Tohoku University Department of Science of Biological Function, Division of Life, 農学部, 教授 (60005626)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsvitamin K / menaquinone-4 (MK-4) / microsome / geranylgeranyl-diphosphate / reduced vitamin K / rat / ラット / ゲラニルゲラニル-二リン酸 / 膵臓 / 顎下腺 / ミトコンドリア
Research Abstract

It was confirmed for the first time by the present study that MK-4 is formed from VK_1 in various tissues (testis, lung, brain, submandibullar gland, heart, spleen, liver, pancreas, and kidney) homegenate system as likely in vivo metabolism described previously by us and suggested by other researchers (Suttie J.W.et at. and Thijssen et at.). The present experiment also revealed that the tissue homegenate factor is indispensable for MK-4 formation, and there was a dose-relationship of used tissue-originated protein that may correspond to the converting enzyme. The fractionation of the homogenate was also undertaken, and the highest activity was observed in the microsomal fraction, and followed by mitochondrial fraction, but the other fractions had almost no activity. Combined these results with the data from the experiment using membrane-solubilizing reagent, Triton X-100, it was suggested that the converting enzyme is probably membrane-associated type, though further studies are necessary. As for the substrate-specificity, the higher activities were observed in the case of VK_1 rather than VK_3 as naphthoquinone ring when GGPP was used as isoprenyl side chain, and also higher activity in the case of GGPP than any other isoprenyl side chains when VK_1 was used as naphthoquinone ring substrate.
Results from the experiment using [8-ring]-^<14>C-VK_1 substrate indicate that the VK analogues such as reduced-MK-4, VK^3, reduced VK^1, and MK-4 oxide could be candidates for intermediates products for final MK-4 formation. We have got these results for the first time in the world by improving the extraction method and by synthesizing the reduced form of VK that has been thought to be unstable in a routine laboratory circumstance.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 駒井三千夫, 古川勇次, 他: "ビタミンK_1, K_2, K_3,経口投与後の組織内メナキノン-4量の増加とその生成機構" ビタミン. 72・2. 57-58 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 江尻昌弘, 駒井三千夫, 古川勇次 他: "ビタミンK_1からメナキノン-4への変換に関する研究" ビタミン. 72・4. 168-168 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 駒井三千夫・古川勇次: "ビタミンKの代謝と体内動態" Clinical Calcium. 9・7編集中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 駒井三千夫, 古川勇次, 他: "無菌ラットおよびマウスにおけるビタミンK_1からメナキノン-4への生体内変換" 無菌生物. 29・2印刷中. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] IKai,H., Komai,M., 他: "Germfree Life and its Ramifications (P.P.447-450)." Hashimoto,K.ほか編(XII ISG Publishing Committee刊),596 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikai, H., Kato, M., Kojima, K., Furukawa, Y., Kimura, S., and Komai, M.: "Abundant distribution of menaqui-none-4 (vitamin K_2) in various organs of germfree mice and rats." in "Germfree Life and Its Ramifications : Ed.by Hashimoto, K., et al., XII ISG Publishing Committee, Shiozawa, Japan. 447-450 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komai, M., Kojima, K., Kato, M., Furukawa, Y., and Kimura, S.: "Menaquinone-4 elevation in various tissues and its formation mechanism after an oral administration of vitamin K_1, K_2, or K_3 in rats." Vitamins. 72 (in Japanese). 57-58 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ejiri, M., Komai, M., Kato, M., Ikai, H., and Furukawa, Y.: "Clarification of the conversion mechanism of vitamin K_1 to menaquinoe-4 in rats." Vitamins. 72 (in Japanese). 168 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komai, M., Ikai, H., Ejiri, M., Kato, M., Mizutani, T., and Furukawa, Y.: "Menaquinone-4 formation from vitamin K_1 in the tissues of germ-free rats and mice." J.Germfree Life & Gnotobiology. 29, (in press) (in Japanese and English abstract). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komai, M.and Furukawa, Y.: "Metabolism and kinetics of vitamin K in mammals." Clinical Calcium. 9, (in press) (in Japanese). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 駒井三千夫,古川勇次,他: "ビタミンK_1,K_2,K_3経口投与後の組織内メナキノン-4量の増加のその生成機構" ビタミン. 72・2. 57-58 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 江尻昌弘,駒井三千夫,古川勇次,他: "ビタミンK_1からメナキノン-4への変換に関する研究" ビタミン. 72・4. 168-168 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 駒井三千夫,古川勇次,他: "ビタミンKの代謝と体内動態" Clinical Calcium. 9・7 (編集中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 猪飼秀行, 駒井三千夫, 古川勇次 他: "ラットのビタミンK欠乏の程度とメナキノン-4の生体内分布" ビタミン. 71(4). 190-190 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 駒井三千夫, 古川勇次, 木村修一: "ラットの生体内におけるビタミンK_1からメナキノン-4の生成機構" ビタミン. 71(9). 445-446 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 駒井三千夫, 古川勇次, 他: "ビタミンK_1,K_2,K_3経口投与後の組織内メナキノン-4量の増加とその生成構構" ビタミン. 72(2). 57-58 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikai,H., Komai,M., ほか: "Germfree Life and its Ramifications(P.P.447-450)" Hashimoto,K.ほか編(XII ISG Publishing Committee)(分担), 596 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Komai,M., Furukawa,Y., et al.: "Abstract of 16th International Congress of Nutrition(P.124)" The International(lmion of Nutritional Sciences., 447 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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