Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose
Glucose 6-phosphate causes translocation of phosphorylase in hepatocytes and inactivates the enzyme synergistically with glucose
复制标题
DOI：
10.1042/bj20031191
复制
发表时间：
2004-01-01
影响因子：
4.1
通讯作者：
Agius, L
中科院分区：
文献类型：
--
作者：
Aiston, S;Green, A;Agius, L
葡萄糖6-P（葡萄糖6-磷酸）在调节糖原合成酶的活化状态及其转位中的作用已有很好的文献记载。在本研究中，我们研究了葡萄糖6-P对肝细胞磷酸化酶的激活状态和区室化的影响。通过葡萄糖激酶过表达或用5-硫代葡萄糖抑制来调节肝细胞中的葡萄糖6-P水平，并且使用AICAR（5-氨基咪唑-4-甲酰胺1-β-D-呋喃核糖苷）测试AMP的作用，AICAR被代谢为AMP类似物。葡萄糖激酶的抑制部分抵消了葡萄糖对磷酸化酶失活和磷酸化酶a从可溶性部分到颗粒部分的易位的影响。葡萄糖激酶过度表达引起的葡萄糖6-P的增加导致磷酸化酶a易位到颗粒中，并与葡萄糖一起对磷酸化酶的失活产生累加效应。它降低了葡萄糖浓度，导致半最大失活从20至11 mM，表明它与葡萄糖协同作用。AICAR激活磷酸化酶，并抵消葡萄糖6-P对磷酸化酶失活的影响。然而，它并没有抵消易位的磷酸化酶的葡萄糖6-P。葡萄糖6-P和AICAR的糖原合成酶的活化状态有相反的效果，但他们有累加效应易位的酶的颗粒。磷酸化酶a和糖原合酶的易位到颗粒之间存在直接相关性，表明这些酶串联易位。总之，葡萄糖6-P导致磷酸化酶的易位和失活，这表明在糖原代谢的调节中的作用比单独的糖原合成酶的调节更复杂。
The role of glucose 6-P (glucose 6-phosphate) in regulating the activation state of glycogen synthase and its translocation is well documented. In the present study, we investigated the effects of glucose 6-P on the activation state and compartmentation of phosphorylase in hepatocytes. Glucose 6-P levels were modulated in hepatocytes by glucokinase overexpression or inhibition with 5-thioglucose and the effects of AMP were tested using AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), which is metabolized to an AMP analogue. Inhibition of glucokinase partially counteracted the effect of glucose both on the inactivation of phosphorylase and on the translocation of phosphorylase a from a soluble to a particulate fraction. The increase in glucose 6-P caused by glucokinase overexpression caused translocation of phosphorylase a to the pellet and had additive effects with glucose on inactivation of phosphorylase. It decreased the glucose concentration that caused half-maximal inactivation from 20 to 11 mM, indicating that it acts synergistically with glucose. AICAR activated phosphorylase and counteracted the effect of glucose 6-P on phosphorylase inactivation. However, it did not counteract translocation of phosphorylase by glucose 6-P. Glucose 6-P and AICAR had opposite effects on the activation state of glycogen synthase, but they had additive effects on translocation of the enzyme to the pellet. There was a direct correlation between the translocation of phosphorylase a and of glycogen synthase to the pellet, suggesting that these enzymes translocate in tandem. In conclusion, glucose 6-P causes both translocation of phosphorylase and inactivation, indicating a more complex role in the regulation of glycogen metabolism than can be explained from regulation of glycogen synthase alone.