Villar-Palasi C
Department of Pharmacology, Medical School, University of Virginia, Charlottesville 22908.
Biochim Biophys Acta. 1991 Nov 12;1095(3):261-7. doi: 10.1016/0167-4889(91)90109-b.
The activation of glycogen synthase by insulin is in many instances stimulated by the presence of extracellular glucose. Previous observations in cell extracts, glycogen pellets and other crude systems suggest that this stimulation may be due to an increase in glucose 6-phosphate, which activates the dephosphorylation of glycogen synthase by protein phosphatases. Using purified rabbit muscle glycogen synthase D and protein phosphatases 1 and 2A, the types responsible for the activation of muscle synthase, it was found that glucose 6-phosphate, at low, physiological concentrations, stimulated the dephosphorylation of glycogen synthase. Both types of phosphatase were stimulated to the same extent when acting on glycogen synthase. The dephosphorylation of other protein substrates of the phosphatases was either not affected or inhibited by glucose 6-phosphate. It appears that the stimulatory effect of glucose 6-phosphate at physiological concentrations is apparently specific for glycogen synthase, and most likely due to an allosteric configuration change of this enzyme which facilitates its dephosphorylation. In addition, the effects of other reported modulators of glycogen synthase dephosphorylation, AMP, ATP and Mg2+, were studied in this 'in vitro' system.
在许多情况下，胰岛素对糖原合酶的激活会受到细胞外葡萄糖的促进。先前在细胞提取物、糖原沉淀和其他粗制体系中的观察结果表明，这种促进作用可能是由于6-磷酸葡萄糖的增加，它能激活蛋白磷酸酶对糖原合酶的去磷酸化作用。利用纯化的兔肌肉糖原合酶D以及负责激活肌肉糖原合酶的1型和2A型蛋白磷酸酶，研究发现，在低生理浓度下，6-磷酸葡萄糖能促进糖原合酶的去磷酸化。这两种磷酸酶作用于糖原合酶时受到的促进程度相同。6-磷酸葡萄糖对磷酸酶的其他蛋白质底物的去磷酸化作用要么没有影响，要么起到抑制作用。看来，生理浓度下6-磷酸葡萄糖的促进作用显然对糖原合酶具有特异性，很可能是由于该酶的变构构型改变，从而有利于其去磷酸化。此外，还在这个“体外”系统中研究了其他已报道的糖原合酶去磷酸化调节剂，即AMP、ATP和Mg2+的作用。
