Lewis S D, Janus T J, Lorand L, Shafer J A
Biochemistry. 1985 Nov 19;24(24):6772-7. doi: 10.1021/bi00345a007.
Thrombin-catalyzed release of activation peptide (AP) from plasma factor XIII was studied to characterize the regulation of this initial step in the activation of factor XIII zymogen (fibrin-stabilizing factor). High-performance liquid chromatography was used to monitor the kinetics of release of AP. Non-cross-linked polymeric fibrins I and II (polymerized des-A- and des-A,B-fibrinogens), physiological substrates of factor XIIIa, were shown to be potent promoters of thrombin-catalyzed release of activation peptide from factor XIII. These promoters are proposed to act by complexing factor XIII and reducing the apparent Km for thrombin-catalyzed release of AP. Since thrombin-catalyzed release of AP is inefficient in the absence of polymerized fibrin, this mode of regulation should minimize formation of factor XIIIa prior to the formation of its fibrin substrates. The promoting activity of polymeric fibrin was rapidly lost when catalytically competent factor XIIIa was allowed to form. This observation suggested the possibility that factor XIIIa catalyzed cross-linking of fibrin inactivates fibrin as a promoter for the thrombin-catalyzed release of AP from factor XIII. Consistent with this view, the thiol reagent S-methyl methanethiosulfonate inactivated factor XIIIa, blocked cross-linking of fibrin, and protected against loss of its promoter activity. This mode of feedback regulation of the activation process by catalytically active factor XIIIa may serve to ensure against continued generation of factor XIIIa after its fibrin substrates have been cross-linked.
研究了凝血酶催化血浆因子 XIII 释放激活肽（AP）的过程，以表征因子 XIII 酶原（纤维蛋白稳定因子）激活这一初始步骤的调控机制。采用高效液相色谱法监测 AP 的释放动力学。因子 XIIIa 的生理性底物非交联聚合纤维蛋白 I 和 II（聚合的去 A - 和去 A、B - 纤维蛋白原）被证明是凝血酶催化因子 XIII 释放激活肽的有效促进剂。这些促进剂被认为通过使因子 XIII 形成复合物并降低凝血酶催化释放 AP 的表观 Km 来发挥作用。由于在没有聚合纤维蛋白的情况下，凝血酶催化释放 AP 的效率较低，这种调控模式应能在因子 XIIIa 的纤维蛋白底物形成之前最大限度地减少其形成。当有催化活性的因子 XIIIa 形成时，聚合纤维蛋白的促进活性迅速丧失。这一观察结果提示，因子 XIIIa 催化的纤维蛋白交联使纤维蛋白作为凝血酶催化因子 XIII 释放 AP 的促进剂失活。与此观点一致，硫醇试剂甲硫氨酸甲基硫代磺酸盐使因子 XIIIa 失活，阻止纤维蛋白交联，并防止其促进活性丧失。催化活性因子 XIIIa 对激活过程的这种反馈调节模式可能有助于确保在其纤维蛋白底物交联后不再持续产生因子 XIIIa。
