...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Soluble phospholipids enhance factor Xa-catalyzed prothrombin activation in solution.
【24h】

Soluble phospholipids enhance factor Xa-catalyzed prothrombin activation in solution.

机译：可溶性磷脂可增强溶液中因子Xa催化的凝血酶原活化。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Acidic phospholipids play an important but incompletely understood role in prothrombin activation. Here we report the effect of short-chain phosphatidylserine (dicaproylphosphatidylserine, C6PS) and the corresponding phosphatidylglycerol (C6PG) and phosphatidylcholine (C6PC) derivatives on the rate of prothrombin activation by factor Xa. The critical micellar concentrations of these short-chained phospholipids have been determined under a variety of conditions that we used for kinetic and structural studies. Under conditions for which these lipids exist in a soluble form, the results demonstrate that: (i) the rate of human prothrombin activation by human factor Xa was enhanced in a calcium-dependent fashion up to 60-fold by addition of C6PS, roughly 20% of the optimal enhancement seen with bovine phosphatidylserine/palmitoyloleoylphosphatidylcholine (25/75 PS/POPC) membranes; (ii) C6PS inhibited the rate of hydrolysis of synthetic factor Xa substrate (S-2765), an effect that was mimicked, but at much lower lipid concentrations, by PS/POPC membranes; (iii) there was no enhancement of prothrombin activation and much less inhibition of hydrolysis of S-2765 by factor Xa in the presence of C6PG or C6PC; and (iv) the thermal denaturation of prothrombin was altered in a calcium-independent but dose-dependent fashion by either C6PS or C6PG. These results have been interpreted in terms of the existence of (a) specific PS binding site(s) on factor Xa (Kd approximately 73 microM) that regulate(s) the activity of this serine protease. Our results do not rule out the possibility that the rate of prothrombin activation is also influenced by a weaker, calcium-independent, and less specific acidic lipid binding site on prothrombin, the occupancy of which results in conformational changes in this protein. The results clearly suggest that PS binding regulates the rate of prothrombin activation.
机译：酸性磷脂在凝血酶原激活中起着重要但尚未完全了解的作用。在这里，我们报告短链磷脂酰丝氨酸（dicaproylphosphatidylserine，C6PS）和相应的磷脂酰甘油（C6PG）和磷脂酰胆碱（C6PC）衍生物对凝血酶原Xa活化率的影响。这些短链磷脂的临界胶束浓度已在我们用于动力学和结构研究的各种条件下确定。在这些脂质以可溶形式存在的条件下，结果表明：（i）通过添加C6PS，人因子Xa激活人凝血酶原的速率以钙依赖的方式提高了60倍，大约为20倍用牛磷脂酰丝氨酸/棕榈酰油酰磷脂酰胆碱（25/75 PS / POPC）膜所见的最佳增强的百分比; （ii）C6PS抑制了合成因子Xa底物（S-2765）的水解速度，这种作用可以被PS / POPC膜模仿，但脂质浓度要低得多; （iii）在存在C6PG或C6PC的情况下，凝血酶原活化没有增强，Xa因子对S-2765的水解的抑制作用更小; （iv）C6PS或C6PG以不依赖钙但剂量依赖的方式改变凝血酶原的热变性。这些结果已根据在因子Xa（Kd约73 microM）上存在（一个或多个）特定PS结合位点的存在来解释，所述XPS调节该丝氨酸蛋白酶的活性。我们的研究结果并不排除凝血酶原激活率也受凝血酶原上弱，不依赖钙且特异性较低的酸性脂质结合位点影响的可能性，凝血酶占有率导致该蛋白构象变化。结果清楚地表明PS结合调节凝血酶原激活的速率。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号