1989 Fiscal Year Final Research Report Summary
Biochemistry and Molecular Biology of Inherited Metabolic Disease.
| Project/Area Number |
61440044
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Gifu University |
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Principal Investigator |
ORII Tadao Gifu University. Pediatrics. Professor., 医学部, 教授 (20045339)
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| Co-Investigator(Kenkyū-buntansha) |
SUKEGAWA Kazuko Gifu University. Pediatrics. Professor., 医学部, 助手 (60115409)
SUZUKI Yasuyuki Gifu University. Pediatrics. Professor., 医学部附属病院, 講師 (00163014)
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| Project Period (FY) |
1986 – 1989
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| Keywords | beta-glucuronidase deficiency / beta-ketothiolase deficiency / Zellweger-like syndrome / cDNA cloning / molecular biology / 分子生物学 |
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| Research Abstract |
This paper described biochemistry and molecular biology of lysosomal, mitochondrial and peroxisomal diseases.
1) The molecular basis for enzyme deficiency in beta-glucuronidase was examined by cDNA cloning. A single substitution was confirmed by sequencing cDNA clones in fibroblasts derived from a MPSVll patient. The nucleotide sequence of the mutant cDNA revealed a C-T transition, an event causing a single Ala^<619>-Val change. This point mutataion was first identified in MPSVll disease.
2)Deficient mitochondrial acetoacetyl-CoA thiolase in fibroblasts from five patients with 3-ketothiolase deficiency was studied. The following results were obtained. a)Activation of acetoacetyl-CoA thiolase activity by K was nil in fibroblasts from all four patients. (b)by immunoblot analysis, this enzyme was not detectable in fibroblasts from three patients, although a very faint band was seen in tissues from another patients. These results demonstrate heterogeneity in the enzyme defect.
3) Full-length cDNA clones for rat and human mitochondrial acetoacetyl-CoA thiolase were isolated and sequenced.
4) A variant case of "Zellweger-like syndrome", with clinical and biochemical findings, consistent with classical Zellweger syndrome, but in whom hepatic peroxisomes were detected by electromicroscopy and immunocytochemically, was reported. This patient is considered to have another type of peroxisomal disorder.
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