Gir S, Slack S M, Turitto V T
Department of Mechanical Engineering, University of Memphis, TN 38152, USA.
Ann Biomed Eng. 1996 May-Jun;24(3):394-9. doi: 10.1007/BF02660888.
A mathematical model has been developed to investigate previously obtained experimental findings relating to the activation of factor X by surface-bound tissue factor--factor VIIa (TF:VIIa) in a tubular flow reactor. In those experiments, factor X was perfused through a microcapillary tube over a range of flow (shear) conditions and the activated product, factor Xa, was measured at the outlet of the tube using a chromogenic assay. In the present study, the steady-state convection-diffusion equation with Michaelis-Menten kinetics used to describe the reaction at the wall was numerically integrated using an implicit method based on linear systems of ordinary differential equations. The results from the numerical analysis indicated that shear rate directly affects both Km and Vmax. Values of Km decreased from 151 to 16 nM as the shear rate increased from 25 to 2400 sec-1. Additionally, there was a twofold increase in Vmax from 1.4 to 3.0 pmol/cm2/min as the shear rate increased from 25 to 300 sec-1. These findings are in contrast with classical enzyme behavior and imply a direct effect of fluid flow on the kinetics of factor X activation.
已开发出一种数学模型，用于研究先前在管式流动反应器中获得的关于表面结合的组织因子-因子VIIa（TF:VIIa）激活因子X的实验结果。在那些实验中，因子X在一系列流动（剪切）条件下通过微毛细管灌注，并使用显色测定法在管的出口处测量活化产物因子Xa。在本研究中，使用基于常微分方程线性系统的隐式方法对用于描述壁面反应的具有米氏动力学的稳态对流扩散方程进行了数值积分。数值分析结果表明，剪切速率直接影响Km和Vmax。随着剪切速率从25秒-1增加到2400秒-1，Km值从151 nM降至16 nM。此外，随着剪切速率从25秒-1增加到300秒-1，Vmax从1.4 pmol/cm2/分钟增加了两倍，达到3.0 pmol/cm2/分钟。这些发现与经典酶行为相反，意味着流体流动对因子X激活动力学有直接影响。
