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Clarification of the conversion mechanism of vitamin K analogues to menaquinone-4, a potent hormone-like substance, in the rat tissues.

Research Project

Project/Area Number 11660119
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  Department of Science of Biological Function, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Associate Professor, 大学院・農学研究科, 助教授 (80143022)

Co-Investigator(Kenkyū-buntansha) ITO Michiko  Department of Biological Chemistry, Faculty of Agriculture, Tohoku University, Technical Official, 農学部, 教務職員 (60250734)
SHIRAKAWA Hitoshi  Department of Science of Biological Function, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Research Associate, 大学院・農学研究科, 助手 (40206280)
FURUKAWA Yuji  Department of Science of Biological Function, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Professor, 大学院・農学研究科, 教授 (60005626)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsvitamin K / menaquinone-4 (MK-4) / microsome / geranylgeranyl-diphosphate / reduced vitamin K_3 / vitamin K_3 / rat / ウシ / メナキノン-4 / ビタミンK_1 / ゲラニルゲラニル二リン酸
Research Abstract

Menaquinone-4 (MK-4) is one of naturally occurring form of vitmin K_2 (MK-n or K2) which is majorly synthesized in the microorganisms, but recently it has been shown that MK-4 is also synthesized from other vitamin K analogues in various tissues of rat and possibly in other mammalian tissues. According to recent investigations undertaken by us and other American and Dutch researchers, MK-4 abundantly distributes than other VK analogues to various tissues in the rats, such as testis, lung, brain, submandibullar gland, heart, spleen, liver, pancreas, and kidney. Recent results also showed that MK-4 is one of potent accelerator of bone formation in the rats, so MK-4 has been thought to be a potent hormone-like substance.
We have newly established an MK-4 formation system in vitro using various tissues of the rats. Substrates for this reaction system are vitamin K_3 (menadione or VK3) or vitamin K_1 (phylloquinone or VK1) as a source for naphthoquinone ring, and geranylgeranyl-diphosphate a … More s a source for isoprenyl side-chain of MK-4, respectively. Supernatant fraction of 900 g of rat kidney homogenate with phophate buffer (pH 7.4) was used as crude enzyme solution. The present experiment undertaken for 2 years revealed that MK-4 production from VK3 was inhibited in a dose-related manner under the presence of warfarin that is an inhibitor for VKs epoxide and VKs reductases. This inhibition was recovered completely by an addition of reducing agent, di-thiothreitol (DTT). This lead us to consider that VK reductase participate in the conversion reaction from VK3 to MK-4, and that VK3-H_2 (reduced form of VK3) and MK-4-H_2 (reduced form of MK-4) might be involved in the reaction pathway as an intermediates. Purification trials of this key enzyme is now going on, and we are observing that the dissociation from the microsomal or mitochondrial membrane fraction made this enzyme much more unstable (less active).
We have partly clarified the conversion mechanism of VKs into MK-4 much more clearly than before, and got useful information to purify this enzyme ([MK-4 synthase] as a tentative name). Further investigations are necessary to understand the physiological role of accumulated MK-4 in various tissues in the rat. Less

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 駒井三千夫,白川仁,古川勇次 他: "ラットの各組織におけるビタミンK_1からメナキノン-4への変換活性"ビタミン. 74. 219-219 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 白川仁,駒井三千夫,古川勇次 他: "神経系の発達におけるビタミンKの関与"ビタミン. 74. 447-449 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 駒井三千夫,白川仁,古川勇次 他: "ラットの各組織におけるビタミンK同族体からメナキノン-4への変換活性"ビタミン. 74. 490-491 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 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 germfree rats and mice."J.Germfree Life & Gnotobiology. 29 (in Japanese and Engligh abstract). 79-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai, M.and Furukawa, Y.: "Metabolism and kinetics of vitamin K in mammals."Clinical Calcium. 9 (in Japanese). 847-852 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai, M., Ejiri, M., Ikai, H., and Furukawa, Y.: "Clarification of the conversion mechanism of vitamin K_1 into menaquinone-4."Vitamins. 73 (in Japanese). 352-353 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai, M., Hiwatashi, K., Ikai, H., Shirakawa, H., Furukawa, Y., and Mizutani, T.: "Conversion activity of vitamin K1 to menaquinone-4 among various tissues of the rat."Vitamins. 74 (in Japanese). 219 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shirakawa, H., Komai, M., and Furukawa, Y.: "Role of vitamin K in the development of nervous systems."Vitamins. 74 (in Japanese). 447-449 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komai, M., Hiwatashi, K., Ikai, H., Ejiri, M., Shirakawa, H., and Furukawa, Y.: "Conversion activity of vitamin K analogues to menaquinone-4 among various tissues of the rat."Vitamins. 74 (in Japanese). 490-491

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koki Kojima, Michio Komai, Masaki Kato, and Yuji Furukawa: "Enzymatic menaquinone-4 formation from vitamin K analogues in various tissues in rats."Manuscript in submission. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michio Komai, Hideyuki Ikai, Masaki Kato, and Yuji Furukawa: "Disappearance rate of menaquinone-4 in various organs by elimination of dietary vitamin K supply in conventional rats."Manuscript in submission. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 駒井三千夫,白川仁,古川勇次 他: "ラットの各組織におけるビタミンK_1からメナキノン-4への変換活性"ビタミン. 74巻・4号. 219-219 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 白川仁,駒井三千夫,古川勇次 他: "神経系の発達におけるビタミンKの関与"ビタミン. 74巻・8号. 447-449 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 駒井三千夫,白川仁,古川勇次 他: "ラットの各組織におけるビタミンK同族体からメナキノン-4への変換活性"ビタミン. 74巻・9号. 490-491 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 駒井三千夫,古川勇次,他: "ビタミンK_1からメナキノン-4への組織内変換機構に関する研究"ビタミン. 73・5&6. 352-353 (1999)

    • Related Report
      1999 Annual Research Report
  • [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. 847-852 (1999)

    • Related Report
      1999 Annual Research Report
  • [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. 79-82 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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