| Project/Area Number |
17K00900
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Eating habits
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
Kamao Maya 神戸薬科大学, 薬学部, 講師 (40299087)
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| Co-Investigator(Kenkyū-buntansha) |
廣田 佳久 芝浦工業大学, システム理工学部, 准教授 (70724277)
須原 義智 芝浦工業大学, システム理工学部, 教授 (30297171)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | ビタミンK / menadione / menaquinone / phylloquinone / 体内動態 / 側鎖切断 / 構造活性相関 / cysteamine誘導体 / 結合タンパク質 / menaquinone-4 / 抱合体 |
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| Outline of Final Research Achievements |
It was found that derivatization of cysteamine (CA) is useful for the measurement of menadione (MD), an intermediate for conversion to active form of vitamin K. It was revealed that a part of MD was metabolized to glucuronide conjugate in cultured cells. It was also suggested that the side chain cleaving enzyme may recognize the double bond of the side chain of vitamin K. Using a vitamin K derivative, we can identify a protein that is a candidate for a molecule involved in side chain cleavage, and visualize the nuclear translocation of the nuclear receptor SXR bound to vitamin K and its export to the nucleus. In addition, it was clarified that the double bond in side chain of vitamin K and the ring structure containing oxygen atom enhance the neural differentiation inducing action.
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| Academic Significance and Societal Importance of the Research Achievements |
ビタミンK摂取源の大部分を占めるビタミンK1（phylloquinone、PK）は体内で側鎖切断により生じたMDを経て、活性型であるビタミンK2（menaquinone-4、MK-4）に変換される。MDがどのように各組織に運搬されるのかは不明であり、その解明に本研究で見出された高感度測定法が利用できる。また、ビタミンKの側鎖切断に関わる酵素は同定されていないが、本研究で側鎖切断に関わる分子の候補となるタンパク質が同定できたことは学術的意義が大きい。さらに、本研究で明らかとなった神経分化誘導作用を高める構造モチーフに関する成果は、神経変性疾患等の治療薬開発に有用な知見を提供するものである。
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