| Project/Area Number |
16380069
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied biochemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
YOSHIMURA Tohru Nagoya University, Graduate School of Bioagricultural Sciences, Professor, 大学院生命農学研究科, 教授 (70182821)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Shun'ichi Osaka University, The Institute of Scientific and Industrial Research, Associate Professor, 産業科学研究所, 助教授 (60263406)
IKEDA Motoko Nagoya University, Graduate School of Bioagricultural Sciences, Associate Professor, 大学院生命農学研究科, 助教授 (20262892)
森山 龍一 名古屋大学, 大学院・生命農学研究科, 助教授 (60191061)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥15,600,000)
Fiscal Year 2006: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | D-amino acid / racemase / D-amino acid oxidase / D-serine dehydratase / yeast / cellular slime mold / silkworm / D-セリン / セリンラセマーゼ / D-アラニン / アラニンラセマーゼ |
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| Research Abstract |
D-Amino acids had been believed to occurr only in lower organisms and to have no functions in higher organisms. However, recently, D-amino acids were discovered also in eukaryotes, including mammals and their physiological roles have been clarified. D-Serine occurs in mammalian brains and serves as an intrinsic coagonist of the N-methyl-D-aspartate (NMDA) glutamate receptors and modulates brain functions. D-Serine is considered to be synthesized by mammalian-type serine racemase and degraded by D-amino acid oxidase, however the detailed metabolic pathway remains unclear. In this research project, we studied the metabolic pathways of D-amino acids in fusion yeast, Schoizosaccharomyces pombe, cellular slime mold, Dyctiostelium discoideum, and silkworm, Bombyx mori. The former two organisms contain mammalian-type serine racemase and D-amino acid oxidase. The S. pombe and D. discoideum serine racemases exhibit the similar properties to those of the mammalian enzyme, for example they catalyze the dehydrataion of D-and L-serine as well as the racemization. To understand the detailed reaction mechanism, we carried out the X-ray crystallography of the yeast serine racemase. We partially purified the silkworm serine racemase and demonstrated that the enzyme catalyzes dominantly racemization and no dehydratation of D-and L-serine. The silkworm serine racemase is the real racemase in this context. During the study of the S. pome D-amino acid oxidase, we found that the enzyme is unique in acting on acidic amino acids. We also found that the budding yeast, Saccharomyces cerevisiae, contains pyridoxal phosphate-dependent D-serine dehydratase, of which primary structure is completely different from that of the bacterial enzymes.
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