Glycogen Storage Disease Type 1b: Disorder of Microsomal membrane Transport.

糖原累积病 1b 型：微粒体膜运输障碍。

• 批准号: 60480239
• 负责人: NARISAWA Kuniaki
• 金额: $ 3.84万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480239/
• 关键词: 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; 好中球機能; 好中球減少; G6P translocase

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 … More 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

糖原累积病（GSD）1b型患者在体外无葡萄糖-6-磷酸酶缺陷，但临床表现与GSD 1a型无明显区别。我们发现GSD 1b的基本缺陷位于微粒体膜上的G6 P转运系统，基于新鲜肝匀浆中葡萄糖-6-磷酸酶活性高度潜伏的发现。本研究建立了微粒体摄取G6 P的方法。在对照组中观察到微粒体对G6 P的显著摄取。而GSD 1b患者则表现为G6 P摄取异常。这些发现提供了直接证据，G6 P特异性运输系统存在于人类microzomal膜和GSD 1b是由于G6 P运输系统的缺陷。目前，鉴定GSD 1型变体中的缺陷基因座需要使用未取代的G6 P和焦磷酸磷酸水解酶进行G6 P和焦磷酸水解酶的测定。 ...更多信息 并破坏微粒体的制备物。为了计算“完整微粒体”的理论磷酸水解酶活性，必须测定M6 P磷酸水解酶活性。我们开发了微量法来测量所有三种磷酸氢酶活性在未经处理和解密的组织中，这可以应用于针吸活检标本。应用本系统检测方法，对3例GSD 1b患者进行了检测。中性化是GSD lb的显著特征。我们研究了中性粒细胞代谢异常和G6 P易位酶缺陷之间的关系。本文报道了3例临床和酶谱表现不同的病人的中性粒细胞代谢爆发。没有G6 P移位酶残余活性的两个兄弟姐妹未能显示出各种己糖单磷酸分流活性的正常刺激。刺激。而G6 P移位酶活性部分缺失的成年患者在刺激后表现出正常的呼吸爆发。这些发现使我们对中性粒细胞中G6 P移位酶的存在及其功能进行了详细的研究。少

项目成果

K. Tada: Biochemical medicine. 33. 212-222 (1985)

K. Tada：生化医学。

K. Narisawa: J. Inher. Met. Dis.9. 297-300 (1986)

K. Narisawa：J. Inher。

K. Narisawa: Enzyme. 38. 177-183 (1987)

K. Narisawa：酶。

成澤邦明: J.Inher.Meatb.Dis. 9. 297-300 (1986)

Kuniaki Narisawa：J.Inher.Meatb.Dis。9. 297-300 (1986)

M. Kikucai, K.Haginoya, S.Miyabayashi, H.Satoh, K.Narisawa ans K.Tada: "Secondary amyloidosis in glycogen storage disease type 1b"

M. Kikucai、K.Haginoya、S.Miyabayashi、H.Satoh、K.Narisawa 和 K.Tada：“糖原累积病 1b 型中的继发性淀粉样变性”