1987 Fiscal Year Final Research Report Summary
Glycogen Storage Disease Type 1b: Disorder of Microsomal membrane Transport.
| Project/Area Number |
60480239
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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 |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NARISAWA Kuniaki @tohoku University School of Medicine, 医学部, 教授 (90004647)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAWA Shinobu Tohoku University School of Medicine, 医学部附属病院, 講師 (60158748)
IGARASHI Yutaka Tohiku University School of Medicine, 医学部, 講師 (70101144)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Glycigen storaye diseose Type 1. Glycogen storage diseose Type16 / G6P translocase / G6Pase / G6Pトランスロケース / 好中球減少症 |
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| Research Abstract |
patients with glycogen storage disease (GSD) type 1b have no defect of glucose-6-phosphatase in vitro, but the clinical findingsare relatively indistinguishable from those of GSD type la. We revealed that a basic defect in GSD 1b was located in the G6P transport system od the microsomal membrane,based on the findings that the glucose-6-phosphatase activity was highly latent in the fresh liver homogenates. In this study, we deceloped a method to investigate th uptake uptake G6P by microsomes. A significant uptake of G6P by microsomes was observed in controls. On the contrary, the patient with GSD 1b showed a negligble uptake of G6P. These findings provide direct evidence the a G6P-specific transport system exists in the human microzomal membrane and that GSD 1b is due to a defect of the G6P transport system. At present the identification of the locus of the defect in the variants of GSD type 1 requires an assay for both the G6P and the pyrophosphate phosphohydrolase using both unterated
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and disrupted preparations of microsomes. The determination of M6P phosphohydrolase activity is essent-ial in order to calculate the theoretical phsphohydrolase activities for the"intact microsomes". We developed micromethods to measure all three phosphohydevlase activities in both the untreated and the the disrypted prepare-tions, which can be applied to needle biopsy specimens. Using thissystematic assay method for G6Pase system, add-itional 3 patients with GSDlb were examined. Neutropenia is a distinctive feature of GSD lb. We investigated the relationship between metabolic abnormalities in the neutrophil and the defect of G6P translocase. The metabo-lic burst in stimulated neutrophils was investigated in 3 patientswith differnt clinical and enzymatic findings. The two siblings who had on residual activity of G6P translocase failed to show the normal stimulation of hexose monophosphata shunt activity with various. stimuli. On the hand, the adult patient with the partial defici-ency of G6P translocase activity showed normal respiratory burst after stimulation. These findings led us to spe-culate on the presence of G6P translocase in neutrophils and its function. Less
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