1989 Fiscal Year Final Research Report Summary
Molecular Biology of Peroxisome Disorders
| Project/Area Number |
63480134
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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 |
Pathological medical chemistry
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| Research Institution | Shinshu University |
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Principal Investigator |
HASHIMOTO Takashi Shinshu. Univ. Sch. Med., Dept. Biochem., 医学部, 教授 (80009935)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAWA Shoko Shinshu. Univ. Sch. Med., Dept. Biochem., 医学部, 助手 (20020745)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Peroxisome disorders / Enzyme deficiency / Very long-chain acyl-CoA synthetase / Acyltransferase / Peroxisome biogenesis / Molecular biology |
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| Research Abstract |
The presence of severe herediatry peroxisome disorders has been recently recognized. The patients with most of these disorders manifests the decreased oxidation rate of very long-chain fatty acids which are degraded by the peroxisomal fatty acid oxidation system. We have shown the patterns of the deficiencies of the individual enzymes of this system in these diseases by immunoblot analysis. In this study, we obtained the following results.
1. It was found that the patterns in neonatal adrenoleukodystrophy were varied among the patients in contrast to other peroxisome disorders. The results suggest that this disease is heterogeneous.
2. Very long-chain fatty acyl-CoA synthetase and dinydroxyacetone phosphate acyltransferase have been considered to be key enzymes for the study on the peroxisomal disorders, But, no enzymological study has been reported. These enzymes were highly purified from rat liver peroxisomes. It was found that very long-chain acyl-CoA synthetase was different from long-chain acyl-CoA synthetase in respect to the molecular and catalytic properties. The purified preparations were still not homogeneous. But these preparations may used for the preparation of the monoclonal antibodies.
3. The study on the mechanism of biogenesid of peroxisones is needed to elucidate the cause of the absence of peroxisome structure in several peroxisome diseases. cDNA for one of the main peroxisomal membrane polypeptide, 70 kDa polypeptide, was cloned and its structure was determined. Several matrix enzymes have a common amino acid sequence, serine-lysine-leucine, at their carboxyl terminus. We that this amino acid sequence was targeting signal for the enzyme localization.
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[Publications] Suzuki, Y., Shimozawa, N., Orii, T., Igarashi, N., Kono, N., Matsui, A., Yokota, S., Hashimoto, T.: "Zellweger-like syndrome with detectable hepatic peroxisomes: a variant form of peroxisomal disorder." J. Pediatr. 113, 841 841-8456, 1988.
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[Publications] Shimozawa, N., Suzuki, Y., Orii, T., Yokota, S., Hashimoto, T.: "Biochemical and morphological aspects of peroxisomes in the human rectal mucosa: diagnosis of Zellweger syndrome simplified by rectal biopsy." Pediatr. Res. 24, 723-727, 1988.
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[Publications] Miyazawa, S., Osumi, T., Hashimoto, T., Ohno, K., Miura, S., Fujiki, Y.: "Peroxisome targeting signal of rat liver acyl-coenzyme A oxidase resides at the carboxy terminus." Mol. Cell. Biol. 46, 383-393, 1988.
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[Publications] Guerroui, S., Aubourg, P., Chen, W. W., Hashimoto, T.: Scotto, J.: "Molecular analysis of peroxisomal beta-oxidation enzymes in infants with peroxisomal disorder indicates heterogeneiety of primary defect." Biochem. Biophys. Res. Commun. 161, 242-251, 1989.
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