| Project/Area Number |
01480150
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | OITA MEDICAL UNIVERSITY |
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Principal Investigator |
TAKESHITA Masazumi OITA MEDICAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY,, 医学部, 教授 (50019551)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRABE Komei OITA MEDICAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY,, 医学部, 助手 (50179058)
YOSHIDA Satoshi OITA MEDICAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY,, 医学部, 助教授 (50158440)
YUBISUI Toshitsugu OITA MEDICAL UNIVERSITY, DEPARTMENT OF BIOCHEMISTRY,, 医学部, 助教授 (00019564)
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| Project Period (FY) |
1989 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | fatty acid elongation / myelination / fatty acid condensation / monoenoic fatty acid / cytochrome b_5 reductase / site directed mutagenesis / 2-ketoacyl-CoA reductase / hypertension / NADHーシトクロムb_5還元酵素 / 2ーケトアシルCoA還元酵素 / 動脈硬化 / モノ不飽和脂肪酸 / CHAPSO / thiolesterase / 副腎白質ジストロフィ- / 白血球 / 極長鎖脂肪酸 / セレブロシド / 粗面小胞体 / 滑面小胞体 / 脂肪酸伸長 / 脂肪酸縮合 / 脂肪酸水酸化 / ブタ動脈壁細胞 / 牛血清アルブミン |
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| Research Abstract |
The microsomal fatty acid elongation system is present ubiquitously in somatic cells. In nervous system it is involved in myilination. In vascular system the system is concemed with atheroscherosis. The elongation reaction consists of four steps:condensation, the first reduction; dehydration and the second reduction. The condensation step has been thought to be a rate limiting step. The first reduction step also possible to be related to regulation. We obtained the following recults in relation to the regulation of fatty acid elongation.
1) We found an activation by SH-reagents and suppression by monoenoic fatty acids of fatty acid elongation. We also found the decrease of fatty acid synthesis in the brain of jimpy mouse and this was regulated in the condensation step.
2) Regulation mechanism of fatty acid elongation in blood vessels has been analyzed. Invouement of fatty acid in blood vessels in terms of hypertension has been shown by wing spontaneously hypertensive rats.
3) Fatty acid elongation in leukocytes and lymphocytes has been analyzed to the level of microsomes. The elongation of 20:0-CoA to 24:0 has been suggested to be distinct to the elongation to 22:0.
4) The NADH-Cytochrome b_5 reductase which is involved in the second step 2-ketoacyl-CoA reductase has been cloaned and its reaction mechanism was analyzed by the method of site directed mutagenesis.
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