2006 Fiscal Year Final Research Report Summary
D-Amino acids in eucaryotic cells: physiological function and its molecular mechanism.
| 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)
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| Project Period (FY) |
2004 – 2006
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| Keywords | D-amino acid / racemase / D-amino acid oxidase / D-serine dehydratase / yeast / cellular slime mold / silkworm |
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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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Research Products
(11 results)
