Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance
Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance
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DOI：
10.1080/13813450902778171
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发表时间：
2009-01-01
影响因子：
3
通讯作者：
Lai, Yu-Chiang
中科院分区：
文献类型：
--
作者：
Jensen, Jorgen;Lai, Yu-Chiang
在哺乳动物中，过量的碳水化合物以糖原的形式储存，而糖原合成酶是将葡萄糖单元掺入糖原颗粒中的酶。糖原合酶活性受磷酸化调节，并由葡萄糖6-磷酸变构激活。不同激酶对9种丝氨酸的磷酸化调节糖原合酶对葡萄糖6-磷酸及其底物UDP-葡萄糖的亲和力。葡萄糖6-磷酸增加酶活性和底物亲和力。胰岛素和运动增加糖原合酶对葡萄糖6-磷酸的亲和力和活性，而高糖原含量和肾上腺素降低对葡萄糖6-磷酸的亲和力和活性。然而，胰岛素、运动和肾上腺素也调节细胞内葡萄糖6-磷酸的浓度，这将影响体内糖原合成酶的活性。重要的是，2型糖尿病与胰岛素刺激的糖原合成酶激活减少有关。这9个磷酸化位点理论上允许糖原合酶具有不同动力学性质的磷酸化构型的512种组合。然而，由于分级磷酸化，体内构型的数量很可能要低得多。不幸的是，许多研究仅报道了用高浓度UDP-葡萄糖测量的糖原合酶活性的数据，这阻碍了关于底物亲和力变化的信息。在本文中，我们讨论了糖原合成酶磷酸化的生理调节和磷酸化模式如何调节糖原合成酶的动力学特性。
In mammals, excess carbohydrate is stored as glycogen and glycogen synthase is the enzyme that incorporates glucose units into the glycogen particle. Glycogen synthase activity is regulated by phosphorylation and allosterically activated by glucose 6-phosphate. Phosphorylation of nine serines by different kinases regulates glycogen synthase affinity for glucose 6-phosphate and its substrate UDP-glucose. Glucose 6-phosphate increases both enzyme activity and substrate affinity. Insulin and exercise increase glycogen synthase affinity for glucose 6-phosphate and activity whereas high glycogen content and adrenaline decrease affinity for glucose 6-phosphate and activity. However, insulin, exercise and adrenaline also regulate intracellular concentration of glucose 6-phosphate which will influence in vivo glycogen synthase activity. Importantly, type 2 diabetes is associated with reduced insulin-stimulated glycogen synthase activation. The nine phosphorylation sites theoretically allow 512 combinations of phosphorylation configurations of glycogen synthase with different kinetic properties. However, due to hierarchal phosphorylation, the number of configurations in vivo is most likely much lower. Unfortunately, many studies only report data on glycogen synthase activity measured with high concentration of UDP-glucose which holds back information about changes in substrate affinity. In this paper we discuss the physiological regulation of glycogen synthase phosphorylation and how the phosphorylation pattern regulates glycogen synthase kinetic properties.