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

糖原沉积病(GSD)1b型患者体外无葡萄糖-6-磷酸酶缺陷，但临床表现与GSD 1a型患者相对较难区分。基于葡萄糖-6-磷酸酶活性在新鲜肝匀浆中高度潜伏的发现，我们发现GSD1b在微体膜的G6P运输系统中存在一个基本缺陷。在这项研究中，我们发展了一种方法来研究微体摄取G6P的情况。在对照组中，观察到微粒体显着摄取G6P。相反，GSD 1b患者表现出可忽略的G6P摄取。这些发现为人类微体细胞膜中存在G6P特异性转运系统以及GSD1b是由于G6P转运系统缺陷提供了直接证据。目前，要确定GSDI型变异体中缺陷的位置，需要使用两种未经修饰的…同时检测G6P和焦磷酸磷酸水解酶更多并打乱了微粒子的制备。M6P磷酸水解酶活性的测定是计算“完整微生物体”的理论磷酸水解酶活性所必需的。我们建立了微量方法来测定未处理的和解密的制剂中所有三种磷酸水解酶的活性，这可以应用于针刺活检标本。用此系统测定G6Pase系统的方法，对另外3例GSD1b患者进行了检测。中性粒细胞减少是GSD lb的一个显著特征。我们探讨了中性粒细胞代谢异常与G6P转位酶缺陷的关系。本文对3例临床和酶学表现不同的受试者进行了中性粒细胞代谢爆发的研究。G6P转位酶残存活性不全的两个兄弟姐妹未能表现出正常刺激单磷酸己糖分流活性的不同。刺激物。G6P转位酶部分缺陷的成人患者刺激后呼吸爆发正常。这些发现使我们对中性粒细胞中G6P转位酶的存在及其功能进行了研究。较少

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