1987 Fiscal Year Final Research Report Summary
MOLECULAR ANALYSIS OF THE DEFECT OF <beta>-OXIDATION ENZYMES IN PEROXISOMAL DISORDERS
| Project/Area Number |
60480141
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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 Department of Biochemistry, Shinshu University School of Medicine, 医学部, 教授 (80009935)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAWA Shoko Department of Biochemistry, Shinshu University School of Medicine, 医学部, 助手 (20020745)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Peroxisomal Disorders0Fatty Acid Oxidation Enzymes / 脂肪酢酸化系酵素 / 酵素欠損 |
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| Research Abstract |
The presence of a new peroxisomal disorders has been recently recognized. The characteristic biochemical deterioration in these diseases in an accumulation of very long-chain fatty acids in body fluids and tissues in the patients. Peroxisomal -oxidation system has a mian role in the degradation of these fatty acids.
In the present project using patients' specimens, the contents of the individual enzymes of this system (acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenease bifunctional enzyme and 3-ketoacyl-CoA thiolase), their expression and the proteolytic processing were examined by immunoblot analysis and pulse-labeling and chase experiments. In the patients with Zellweger syndrome and infantile Refsum disease who lack peroxisome structure, all three enzymes were synthesized but disappeared rapidly. The absence of the specific enzyme was proved in some diseases. They are now called as acyl-CoA oxidase deficiency and 3-ketoacyl-CoA thiolase deficiency. In X-linked adrenoleukodystrophy, all of the enzymes were detected. The etiology of this disease is now suspected to the disfunction of the activation of very long-chain fatty acids. In neonatal adrenoleukodystrophy and rhizomelic chondrodysplasia punctata, the characteristic patterns in the enzyme defect including the absence of the proteolytic processing of 3-ketoacvl-CoA thiolase were found. This work was conducted in collaboration with many groups.
The cDNAs and genes for rat enzymes were isolated and characterized for the purpose of the gene analysis of the human disease.
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