Studies on the biosynthetic enzyme of the novel bioactive substance D-glutamate that is related to heart diseases
| Project/Area Number |
18K06117
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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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| Review Section |
Basic Section 43030:Functional biochemistry-related
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | グルタミン酸ラセマーゼ / D-グルタミン酸合成酵素 / D-グルタミン酸 / L-セリン/L-スレオニンデヒドラターゼ / アミノ酸ラセマーゼ / アミノ酸デヒドラターゼ / D-アミノ酸 / 心臓 / L-セリンデヒドラターゼ / デヒドラターゼ |
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| Outline of Final Research Achievements |
Previously, we first identified D-glutamate cyclase as its degradative enzyme in mammals, whereas its biosynthetic pathway in mammals is unclear. Glutamate racemase is a most probable candidate, which catalyzes interconversion between D-glutamate and L-glutamate. Here, we identified the cDNA encoding L-serine dehydratase-like (SDHL) as the first mammalian clone with glutamate racemase activity.
Rat SDHL was expressed in Escherichia coli, and the enzymatic properties of the recombinant were characterized. The results indicated that rat SDHL is a multifunctional enzyme with glutamate racemase activity in addition to L-serine/L-threonine dehydratase activity. Further experiments using cultured mammalian cells confirmed that D-glutamate was synthesized and L-serine and L-threonine were decomposed. It was also found that SDHL contributes to homeostasis of several other amino acids.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は以前に、生体内で D-グルタミン酸（D-Glu）を分解する酵素を同定し、この酵素の発現レベルが心不全モデルマウスで低下していることなどを明らかにした。すなわち、哺乳類は D-Glu の合成および分解経路を備えており、心機能に関連する新奇な生理活性物質として D-Glu を利用していると考えられる。
本研究では、ラット Glu ラセマーゼ（L-Glu と D-Glu の相互変換を触媒する酵素）の酵素学的性質・機能のほか、種々のアミノ酸の細胞内および細胞外含量に与える影響を解析した。本研究成果は、心不全に至る分子機構の解明や、心不全の予防薬の開発にもつながる可能性を秘めていると考えられる。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Prenatal expression of D-aspartate oxidase causes early cerebral D-aspartate depletion and influences brain morphology and cognitive functions at adulthood2020
Author(s)
Arianna De Rosa, Francesca Mastrostefano, Anna Di Maio, Tommaso Nuzzo, Yasuaki Saitoh, Masumi Katane, Andrea M. Isidori, Viviana Caputo, Pina Marotta, Geppino Falco, Maria Egle De Stefano, Hiroshi Homma, Alessandro Usiello, Francesco Errico
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Journal Title
Amino Acids
Volume: 52
Pages: 597-617
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Exploring D-aspartate and D-serine cerebral metabolism in four mouse models of autism spectrum disorder2019
Author(s)
Tommaso Nuzzo, Daniela Punzo, Mattia Miroballo, Masumi Katane, Masae Sekine, Yasuaki Saitoh, Arianna De Rosa, Anna Di Maio, Martina Garofalo, Francesco Errico, Alessandro Gozzi, Jean Pierre Mothet, Hiroshi Homma, Alessandro Usiello
Organizer
IDAR 2019 (The 4th International Conference of D-Amino Acid Research)
Related Report
Int'l Joint Research
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[Presentation] Anticipated expression of D-aspartate oxidase since embryonic stage drastically reduces D-aspartate levels in the mouse brain and influences spatial memory at adulthood2019
Author(s)
Arianna De Rosa, Tommaso Nuzzo, Francesca Mastrostefano, Anna Di Maio, Yasuaki Saitoh, Francesco Napolitano, Masumi Katane, Andrea Isidori, Viviana Caputo, Maria Egle De Stefano, Hiroshi Homma, Alessandro Usiello, Francesco Errico
Organizer
IDAR 2019 (The 4th International Conference of D-Amino Acid Research)
Related Report
Int'l Joint Research / Invited
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