Lei K J, Chen H, Pan C J, Ward J M, Mosinger B, Lee E J, Westphal H, Mansfield B C, Chou J Y
Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1996 Jun;13(2):203-9. doi: 10.1038/ng0696-203.
Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and to develop future therapeutic approaches. By examining G6Pase in the liver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate proteins which are tightly coupled. We propose a modified translocase catalytic unit model for G6Pase catalysis.
1a型糖原贮积病（GSD-1a）是由微粒体葡萄糖-6-磷酸酶（G6Pase）缺乏引起的，G6Pase是葡萄糖稳态中的关键酶。为了了解这种疾病的发病机制、阐明G6Pase催化的机制并开发未来的治疗方法，构建了一种模拟人类GSD-1a患者病理生理学的G6Pase基因敲除小鼠。通过检测肝脏和肾脏（主要的糖异生组织）中的G6Pase，我们证明葡萄糖-6-磷酸的转运和水解是由紧密偶联的不同蛋白质完成的。我们提出了一种G6Pase催化的改良转位酶催化单元模型。
