葡萄糖激酶受葡萄糖激酶调节蛋白的调控
中文名称
通路描述
葡萄糖激酶 (GCK1) 受葡萄糖激酶调节蛋白 (GKRP) 的负调控，该蛋白可逆地结合酶形成无活性复合物。结合受到果糖 6-磷酸和赤藓糖醇 6-磷酸 (因此这些分子的高浓度倾向于降低 GCK1 活性) 的刺激，并受到果糖 1-磷酸的抑制 (因此该分子的高浓度倾向于增加 GCK1 活性)。一旦形成，复合物被转运至细胞核。在高葡萄糖浓度的存在下，细胞核内的 GCK1:GKRP 复合物解离，释放 GCK1 使其返回细胞质。在存在这些条件下，游离的 GKRP 也被认为返回细胞质，但实验上尚未确认。该捕获过程的潜在生理作用是在低葡萄糖条件下减少肝细胞中葡萄糖与葡萄糖 6-磷酸之间的 futile cycling，并减少肝细胞和胰腺β细胞中葡萄糖水平上升与葡萄糖磷酸化启动之间的滞后时间 (Brocklehurst et al. 2004; Shiota et al. 1999)。
英文描述
Regulation of Glucokinase by Glucokinase Regulatory Protein Glucokinase (GCK1) is negatively regulated by glucokinase regulatory protein (GKRP), which reversibly binds the enzyme to form an inactive complex. Binding is stimulated by fructose 6-phosphate and sorbitol 6-phosphate (hence high concentrations of these molecules tend to reduce GCK1 activity) and inhibited by fructose 1-phosphate (hence a high concentration of this molecule tends to increase GCK1 activity). Once formed, the complex is translocated to the nucleus. In the presence of high glucose concentrations, the nuclear GCK1:GKRP complex dissociates, freeing GCK1 to return to the cytosol. The free GKRP is thought also to return to the cytosol under these conditions, but this return has not been confirmed experimentally. Possible physiological roles for this sequestration process are to decrease futile cycling between glucose and glucose 6 phosphate in hepatocytes under low-glucose conditions, and to decrease the lag between a rise in intracellular glucose levels and the onset of glucose phosphorylation in both hepatocytes and pancreatic beta cells (Brocklehurst et al. 2004; Shiota et al. 1999).
所含基因
29 个基因