Gilboe D P, Nuttall F Q
Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Arch Biochem Biophys. 1988 Jul;264(1):302-9. doi: 10.1016/0003-9861(88)90598-x.
Glycogen particle synthase phosphatase activity is stimulated by glucose with an A0.5 of approximately 27 mM. The A0.5 is higher than the usual concentrations present in the liver. However, in vitro, certain methylxanthines such as caffeine or theophylline reduce the glucose A0.5 to approximately 10 mM, a concentration well within the normal range of liver glucose concentrations. Methylxanthines do not affect the maximum stimulation by glucose (2.3-fold greater than control rate). The phosphatase reaction also is inhibited by ATP-Mg (I0.5 = 0.1 mM). In the present studies, we have determined the interaction of these effectors. The presence of ATP-Mg at a concentration of 3 mM only slightly reduced the maximal stimulation by glucose. The A0.5 for glucose was unaffected (24 mM). The synergistic effect of caffeine with glucose also was not changed by the presence of ATP-Mg. The A0.5 for glucose was reduced to 11 mM, similar to that in the absence of ATP-Mg. In addition, maximum stimulation by glucose was unchanged. Similar results were obtained when theophylline replaced caffeine. We conclude that the ATP-Mg binding site on either the phosphatase or its substrate, synthase D, does not influence the glucose and methylxanthine binding sites. Effectively, ATP-Mg increased the range over which glucose stimulates the phosphatase activity. In the presence of ATP-Mg, the maximum stimulation by glucose is approximately 7-fold; whereas, in the absence of ATP-Mg it is approximately 2.3-fold. Thus, ATP-Mg may serve to increase the sensitivity of the synthase phosphatase reaction to glucose regulation under in vivo conditions.
糖原颗粒合酶磷酸酶活性受到葡萄糖的刺激，其半最大激活浓度（A0.5）约为27 mM。该A0.5高于肝脏中通常存在的浓度。然而，在体外，某些甲基黄嘌呤如咖啡因或茶碱可将葡萄糖的A0.5降低至约10 mM，这一浓度处于肝脏葡萄糖浓度的正常范围内。甲基黄嘌呤不影响葡萄糖的最大刺激作用（比对照速率高2.3倍）。磷酸酶反应也受到ATP-Mg的抑制（半抑制浓度I0.5 = 0.1 mM）。在本研究中，我们确定了这些效应物之间的相互作用。3 mM浓度的ATP-Mg仅略微降低了葡萄糖的最大刺激作用。葡萄糖的A0.5未受影响（24 mM）。咖啡因与葡萄糖的协同作用也不受ATP-Mg存在的影响。葡萄糖的A0.5降至11 mM，与不存在ATP-Mg时相似。此外，葡萄糖的最大刺激作用未改变。当茶碱替代咖啡因时，获得了类似的结果。我们得出结论，磷酸酶或其底物合酶D上的ATP-Mg结合位点不影响葡萄糖和甲基黄嘌呤的结合位点。实际上，ATP-Mg增加了葡萄糖刺激磷酸酶活性的范围。在存在ATP-Mg的情况下，葡萄糖的最大刺激作用约为7倍；而在不存在ATP-Mg的情况下，约为2.3倍。因此，ATP-Mg可能有助于在体内条件下增加合酶磷酸酶反应对葡萄糖调节的敏感性。
