Homotropic allosteric regulation in monomeric mammalian glucokinase.
Homotropic allosteric regulation in monomeric mammalian glucokinase.
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DOI：
10.1016/j.abb.2011.11.007
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发表时间：
2012-03-15
影响因子：
3.9
通讯作者：
Miller, Brian G.
中科院分区：
文献类型：
--
作者：
Larion, Mioara;Miller, Brian G.
关键词：
葡萄糖激酶催化依赖于ATP的葡萄糖磷酸化，这一化学转化代表了肝脏和胰腺糖酵解代谢的限速步骤。葡萄糖激酶是葡萄糖稳态的中心调节器，它与两种疾病状态--青年成熟期糖尿病(MODY)和婴儿期持续性高胰岛素血症(PHHI)的相关性得到了证实。哺乳动物葡萄糖激酶受葡萄糖的同质变构调节--葡萄糖6-磷酸生产的稳态速度不是双曲线，而是对葡萄糖浓度的增加表现出S形反应。葡糖激酶表现出的正协同效应很耐人寻味，因为这种酶在生理条件下是作为单体发挥作用的，并且只包含一个葡萄糖结合部位。尽管在单体酶中存在几种动力学协同作用模型，但对于葡糖激酶中变构调节的机制还没有达成共识。一些研究人员在过去45年中收集的实验证据支持葡萄糖激酶支架的协同性和缓慢的构象重组之间的联系。在这篇综述中，我们总结了最近的X射线结晶学、平衡前动力学和高分辨率核磁共振研究导致的葡糖激酶变构调节的研究进展。最后，我们简要讨论了尚未回答的关于哺乳动物葡萄糖激酶动力学协同作用的机制基础的问题。
Glucokinase catalyzes the ATP-dependent phosphorylation of glucose, a chemical transformation that represents the rate-limiting step of glycolytic metabolism in the liver and pancreas. Glucokinase is a central regulator of glucose homeostasis as evidenced by its association with two disease states, maturity onset diabetes of the young (MODY) and persistent hyperinsulinemia of infancy (PHHI). Mammalian glucokinase is subject to homotropic allosteric regulation by glucose — the steady-state velocity of glucose 6-phosphate production is not hyperbolic, but instead displays a sigmoidal response to increasing glucose concentrations. The positive cooperativity displayed by glucokinase is intriguing since the enzyme functions as a monomer under physiological conditions and contains only a single binding site for glucose. Despite the existence of several models of kinetic cooperativity in monomeric enzymes, a consensus has yet to be reached regarding the mechanism of allosteric regulation in glucokinase. Experimental evidence collected over the last 45 years by a number of investigators supports a link between cooperativity and slow conformational reorganizations of the glucokinase scaffold. In this review, we summarize advances in our understanding of glucokinase allosteric regulation resulting from recent X-ray crystallographic, pre-equilibrium kinetic and high-resolution nuclear magnetic resonance investigations. We conclude with a brief discussion of unanswered questions regarding the mechanistic basis of kinetic cooperativity in mammalian glucokinase.
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DOI：
10.1111/j.1432-1033.1977.tb11916.x
发表时间：
1977-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BUC, J;RICARD, J;MEUNIER, JC
通讯作者：
MEUNIER, JC
影响因子：
8.2
作者：
Davis, EA;Cuesta-Muñoz, A;Matschinsky, FM
通讯作者：
Matschinsky, FM
影响因子：
64.8
作者：
FROGUEL, P;VAXILLAIRE, M;COHEN, D
通讯作者：
COHEN, D
影响因子：
7.7
作者：
Cuesta-Muñoz, AL;Huopio, H;Laakso, M
通讯作者：
Laakso, M
影响因子：
4.8
作者：
Ardehali, H;Yano, Y;Granner, DK
通讯作者：
Granner, DK