• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of vitamin K side chain cleavage enzyme aiming at unified understanding of vitamin K synthesis mechanism

Research Project

Project/Area Number 16K18924
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Environmental and hygienic pharmacy
Research InstitutionShibaura Institute of Technology

Principal Investigator

HIROTA Yoshihisa  芝浦工業大学, システム理工学部, 助教 (70724277)

Co-Investigator(Renkei-kenkyūsha) SUHARA Yoshitomo  芝浦工業大学, システム理工学部・生命科学科, 教授 (30297171)
Research Collaborator OKANO Toshio  神戸薬科大学, 薬学部, 教授 (20131542)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsビタミンK / 側鎖切断酵素 / 2',3'-PKH2 / 代謝機構 / UBIAD1 / MK-4 / MD / 遺伝子改変 / 小腸 / オミクス解析 / 遺伝子改変動物 / 腸
Outline of Final Research Achievements

In humans and mice, ingested PK is MD which has a side chain cleaved in the small intestine and has no side chains and is converted into MK-4 by UBIAD1 in each tissue. Vitamin K side chain cleavage mechanism has not been elucidated so far and search of side chain cleavage enzymes is also difficult. So we elucidated the in vivo metabolic mechanism of 2',3'-PKH2. As a result, it was found that 2',3'-PKH2 is a vitamin K derivative not undergoing a side chain cleavage reaction, since MD which is an intermediate of the MK-4 conversion reaction was not detected at all in the lymph fluid .
From the results of this study, it is considered that the vitamin K side chain cleavage enzyme selectively recognizes and cleaves double bonds at the 2nd and 3rd positions present in the side chain of PK. If vitamin K side chain cleavage enzyme can be identified in future, it is clarified what kind of mechanism the ingested vitamin K is metabolically absorbed and exercises physiological function.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (28 results)

All 2018 2017 2016 Other

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Paradigm Shift of Vitamin K Research: Discovery of New Biological Activities of Vitamin K and Synthesis of the Analogues2017

    • Author(s)
      須原義智,廣田佳久
    • Journal Title

      KAGAKU TO SEIBUTSU

      Volume: 56 Issue: 1 Pages: 26-32

    • DOI

      10.1271/kagakutoseibutsu.56.26

    • NAID

      130007535659

    • ISSN
      0453-073X, 1883-6852
    • Year and Date
      2017-12-20
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 25-hydroxyvitamin D3 may Function via Genomic and Non-Genomic actions.2017

    • Author(s)
      Hirota Y*, Suhara Y, Osakabe N, Sakaki T*, Okano T*.
    • Journal Title

      Anat. Physiol.

      Volume: 7 Issue: 04 Pages: 278-280

    • DOI

      10.4172/2161-0940.1000278

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities2017

    • Author(s)
      Sakane, Rie; Kimura, Kimito; Hirota, Yoshihisa; Ishizawa, Michiyasu; Takagi, Yuta; Wada, Akimori; Kuwahara, Shigefumi; Makishima, Makoto; Suhara, Yoshitomo
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 27 Issue: 21 Pages: 4881-4884

    • DOI

      10.1016/j.bmcl.2017.09.038

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flavan 3-ol delays the progression of disuse atrophy induced by hindlimb suspension in mice2017

    • Author(s)
      Ito Mao、Kudo Naoto、Miyake Yuji、Imai Tatsuya、Unno Tomoki、Yamashita Yoko、Hirota Yoshihisa、Ashida Hitoshi、Osakabe Naomi
    • Journal Title

      Experimental Gerontology

      Volume: 98 Pages: 120-123

    • DOI

      10.1016/j.exger.2017.07.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ビタミンKの生体内代謝機構に関する研究 (奨励賞受賞講演)2017

    • Author(s)
      廣田佳久
    • Journal Title

      VITAMINS

      Volume: 91 Issue: 4 Pages: 225-227

    • DOI

      10.20632/vso.91.4_225

    • NAID

      130006729306

    • ISSN
      0006-386X, 2424-080X
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ビタミンD はSREBP/SCAP の分解を誘導することで脂質代謝を制御する,2017

    • Author(s)
      廣田佳久,伊東優貴,須原義智
    • Journal Title

      ビタミン誌

      Volume: 91 Pages: 617-620

    • NAID

      130007501861

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice2017

    • Author(s)
      Y Hirota K Nakagawa S Mimatsu N Sawada T Sakaki N Kubodera M Kamao N Tsugawa Y Suhara T Okano
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 483 Issue: 1 Pages: 359-365

    • DOI

      10.1016/j.bbrc.2016.12.139

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells.2017

    • Author(s)
      Kimura K, Hirota Y, Kuwahara S, Takeuchi A, Tode C, Wada A, Osakabe N, Suhara Y
    • Journal Title

      J Med Chem

      Volume: 60 Issue: 6 Pages: 2591-2596

    • DOI

      10.1021/acs.jmedchem.6b01717

    • NAID

      130007472633

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry Using Pseudo Multiple Reaction Monitoring.2017

    • Author(s)
      Kamao M, Hirota Y, Suhara Y, Tsugawa N, Nakagawa K, Okano T, Hasegawa H.
    • Journal Title

      Anal Sci

      Volume: 33 Pages: 1-8

    • NAID

      130005796381

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ビタミンK合成酵素UBIAD1タンパク質の機能解析2017

    • Author(s)
      廣田佳久,中川公恵,澤田夏美,奥田直子,須原義智,内野由理,木本貴士,舟橋伸昭,鎌尾まや,津川尚子,岡野登志夫
    • Journal Title

      ビタミン誌

      Volume: 91 Pages: 1-5

    • NAID

      130007413127

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ビタミンKの生体内代謝機構に関する研究912017

    • Author(s)
      廣田佳久
    • Journal Title

      ビタミン誌

      Volume: 91 Pages: 225-227

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ビタミンKによる神経幹細胞からニューロンへの選択的な分化誘導機構に対するL型Caチャネルの寄与2018

    • Author(s)
      廣田佳久、高木勇太、井田有香、古川絢子、須原義智
    • Organizer
      第138回 日本薬学会年会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 水素添加したビタミンK1(2', 3'-PKH2)の代謝機構2017

    • Author(s)
      廣田佳久、中川公恵、須原義智、岡野登志夫
    • Organizer
      第137回日本薬学会年会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] ビタミンKの生体内代謝機構に関する研究2017

    • Author(s)
      廣田佳久
    • Organizer
      第69回日本ビタミン学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ビタミンK1水素付加物(2', 3'-PKH2)の生体内代謝機構2017

    • Author(s)
      廣田佳久、中川公恵、須原義智、岡野登志夫
    • Organizer
      第69回日本ビタミン学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビタミンK1水素付加物の生体内代謝機構の解析2017

    • Author(s)
      請川翔一,伊津野左奈永,須原義智,岡野登志夫,廣田佳久
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メチル基を有する芳香環を導入したビタミンK誘導体によるニューロンへの分化誘導作用の検討2017

    • Author(s)
      髙木勇太,井田有香,木村キミト,須原義智,廣田佳久
    • Organizer
      第61回日本薬学会関東支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビタミンK1水素付加物(2', 3'-PKH2)の生体内代謝機構の解析2017

    • Author(s)
      請川翔一,海野裕真,伊津野左奈永,須原義智,岡野登志夫,廣田佳久
    • Organizer
      第22回日本フードファクター学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メチル基を有する芳香環を側鎖末端に導入したビタミンK誘導体による神経分化活性評価2017

    • Author(s)
      髙木勇太,井田有香,木村キミト,須原義智,廣田佳久
    • Organizer
      第22回日本フードファクター学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cyp27b1およびVdr欠損マウスの比較から1α,25D3は軟骨形成においてnongenomic作用を示す2017

    • Author(s)
      廣田佳久,中川公恵,榊利之,須原義智,岡野登志夫
    • Organizer
      第22回日本フードファクター学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 水素付加したビタミンK1の生体内代謝機構の解析2017

    • Author(s)
      廣田佳久、中川公恵、須原義智、岡野登志夫
    • Organizer
      2017年度 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビタミンK合成機構解明を目指した側鎖切断酵素の探索2016

    • Author(s)
      廣田佳久、津川尚子、中川公恵,鎌尾まや、須原義智、岡野登志夫
    • Organizer
      第21回日本フードファクター学会
    • Place of Presentation
      富山国際会議場 大手町フォーラム
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report
  • [Presentation] ビタミンK2変換酵素UBIAD1タンパク質の機能解析2016

    • Author(s)
      廣田佳久、中川公恵、澤田夏美、須原義智、岡野登志夫
    • Organizer
      第89回 日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ビタミンK2合成酵素UBIAD1タンパク質の機能解析2016

    • Author(s)
      廣田佳久、中川公恵、澤田夏美、須原義智、岡野登志夫
    • Organizer
      フォーラム2016:衛生薬学・環境トキシコロジー
    • Place of Presentation
      昭和大学 旗の台キャンパス
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] ビタミンK合成酵素UBIAD1タンパク質の機能解析2016

    • Author(s)
      廣田佳久、中川公恵、澤田夏美、須原義智、岡野登志夫
    • Organizer
      第68回 日本ビタミン学会
    • Place of Presentation
      富山国際会議場 大手町フォーラム
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] ビタミンK合成酵素のタンパク質機能解析2016

    • Author(s)
      廣田佳久、中川公恵、須原義智、岡野登志夫
    • Organizer
      第60回 日本薬学会関東支部大会
    • Place of Presentation
      東京大学 山上会館
    • Related Report
      2016 Research-status Report
  • [Remarks] 芝浦工業大学 「QOL向上とライフサイエンス」コンソーシアム

    • URL

      http://plus.shibaura-it.ac.jp/sitrbp/Lifesci/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 芝浦工業大学 システム理工学部 生命科学科 生化学研究室

    • URL

      http://www.shibaura-it.ac.jp/faculty/systems_engineering_and_science/bioscience_and_engineering_bioscience/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi