| Project/Area Number |
18K14900
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | University of Toyama |
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Principal Investigator |
Kawaguchi Kosuke 富山大学, 学術研究部薬学・和漢系, 助教 (80624866)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ABCタンパク質 / ペルオキシソーム / 極長鎖脂肪酸CoA / プロテオリポソーム / メタノール資化性酵母 / 極長鎖脂肪酸 |
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| Outline of Final Research Achievements |
Dysfunction of peroxisomal ATP-binding cassette (ABC) protein, ABCD1, causes a severe neurodegenerative disease, X-linked adrenoleukodystophy. ABCD1 is suggested to be involved in the transport of very long chain fatty acyl-CoA, but the precise mechanism of the transport has yet to be elucidated.
It is demonstrated that ABCD1 transports very long chain fatty acyl-CoA as free very long chain fatty acid into peroxisomes through the hydrolysis of very long chain fatty acyl-CoA mediated by the acyl-CoA thioesterase activity of ABCD1 itself and that acyl-CoA thioesterase activity of ABCD1 is indispensable for this transport system.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトABCD1のもつATPase活性とアシルCoAチオエステラーゼ活性が協調して極長鎖脂肪酸CoAをペルオキシソーム内へと輸送する分子機構について初めて明らかとした。また、蛍光基NBDで標識したNBD-パルミトイルCoAを基質として用いることで、ABCD1が加水分解された遊離脂肪酸を輸送基質とすることを直接検出することに初めて成功した。
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