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首页> 外文期刊>Platelets >Glyoxylate lowers metabolic ATP in human platelets without altering adenylate energy charge or aggregation
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Glyoxylate lowers metabolic ATP in human platelets without altering adenylate energy charge or aggregation

机译：乙醛酸酯降低人血小板中的代谢ATP，而不会改变腺苷酸的能量电荷或聚集

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摘要

Human blood platelets adhere to exposed collagen at the site of vascular injury, initiating a signaling cascade leading to fibrinogen activation, secretion of granules and aggregation, thus producing a stable thrombus. All these steps require metabolic ATP. In this study we have labeled the metabolic pool of ATP with nucleotides, treated platelets with various inhibitors and have monitored their ability to be activated. Incubating platelets with glyoxylate dramatically reduced the ATP level without a change in the adenylate energy charge (AEC). This reduction of ATP did not affect ADP-induced primary or secondary aggregation, whereas glyoxal, methyl glyoxal, or the combination of antimycin plus deoxyglucose reduced both ATP and AEC and inhibited aggregation. The reduction of ATP by glyoxylate was almost quantitatively matched by an increase in hypoxanthine without elevation of ADP. AMP, IMP or inosine, acetoacetate, aspartate, or glutamate had no effect on glyoxylate-induced breakdown of ATP, while pyruvate stopped the ATP reduction fast and efficiently. Glyoxylate also lowered the citrate content. The glyoxylate-induced breakdown of ATP coincided with an increase in fructose-1,6-bisphosphate, indicating that the phosphofructokinase reaction was the main ATP-consuming step. Glyoxylate was a substrate for lactate dehydrogenase although with a Km almost 100 times higher than pyruvate. We suggest that glyoxylate primarily competes with pyruvate in the pyruvate dehydrogenase reaction, thus lowering the citrate concentration, which in turn activates phosphofructokinase. Clearly, lowering of ATP in the cytosol by more than 50% does not affect platelet aggregation provided that the AEC is not reduced.
机译：人血小板在血管损伤部位粘附在暴露的胶原蛋白上，引发信号传导级联反应，导致纤维蛋白原活化，颗粒分泌和聚集，从而产生稳定的血栓。所有这些步骤都需要代谢ATP。在这项研究中，我们用核苷酸标记了ATP的代谢库，并用各种抑制剂处理了血小板，并监测了它们的活化能力。用乙醛酸酯孵育血小板会显着降低ATP水平，而腺苷酸能电荷（AEC）不变。 ATP的这种降低不会影响ADP诱导的一级或二级聚集，而乙二醛，甲基乙二醛或抗霉素与脱氧葡萄糖的组合会降低ATP和AEC并抑制聚集。乙醛酸对ATP的减少几乎与次黄嘌呤的增加在定量上相匹配，而ADP却没有升高。 AMP，IMP或肌苷，乙酰乙酸盐，天冬氨酸盐或谷氨酸对乙醛酸诱导的ATP分解没有影响，而丙酮酸则快速有效地阻止了ATP的还原。乙醛酸酯还降低了柠檬酸盐的含量。乙醛酸诱导的ATP分解与果糖-1,6-双磷酸酯的增加同时发生，表明磷酸果糖激酶反应是消耗ATP的主要步骤。乙醛酸是乳酸脱氢酶的底物，尽管Km比丙酮酸高近100倍。我们建议乙醛酸在丙酮酸脱氢酶反应中主要与丙酮酸竞争，从而降低柠檬酸浓度，进而激活磷酸果糖激酶。显然，只要不降低AEC，胞浆中的ATP降低50％以上不会影响血小板聚集。

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