钙离子振荡对肝糖磷酸化酶激活的随机效应研究

The Stochastic Effects of Ca^(2+) Oscillations on Activation of Glycogen Phosphorylase

在复杂生化系统的研究过程中,仿真与建模变得越来越重要.对于参与分子数量比较大的生化系统,通常可以采用常微分方程来解决这一问题.对于分子数量比较小的系统,离散粒子基础上的随机模拟方法更精确.然而目前还没有明确的理论方法来确定,对于实际问题用哪种方法能得到更合理的结果.因此需要在一个普遍研究的体系中,通过Ca^(2+)振荡传导信号来研究从随机行为到确定行为的过渡过程.本文以肝细胞中Ca^(2+)振荡对肝糖磷酸化酶激活随机效应为例,讨论了利用随机微分方程来解决分子数量比较小的生化系统的仿真与建模问题,利用细胞内Ca^(2+)有关的Li-Rinzel随机模型,研究了在磷酸化酶降解肝糖的磷酸化-去磷酸化作用循环过程中,三磷酸肌醇受体通道(IP_3R)释放Ca^(2+)的调控作用.结果表明,肝糖磷酸化酶的激活率随受体通道IP_3R的总数增大而减弱,而且三磷酸肌醇浓度比较小时出现相干共振.

Simulation and modeling is becoming more and more important when studying complex biochemical systems. Most often, ordinary differential equations are employed for this purpose. However, these are only applicable when the numbers of participating molecules in the biochemical systems are large enough to be treated as concentrations. For smaller systems, stochastic simulations based on discrete particle are more accurate. Unfortunately, there are no general rules for determining which method should be employed for a specific problem to get the most realistic result. Therefore, we study the transition from stochastic to deterministic behavior in a widely studied system by calcium oscillation transmission signals. Used stochastic effects of calcium oscillations on glycogen phosphorylase activation in hepatocytes as an example, we attempted to solve the problem of simulation and modeling in the biochemical system with small number of molecules by stochastic differential equation. The possible role of Ca2＋ released from the inositol 1, 4, 5-trisphosphate （IP3） receptor channel in the regulation of the phosphorylation-dephosphorylation cycle process involved in glycogen degradation by glycogen phosphorylase have theoretically investigated using stochastic the Li-Rinzel model for cytosolic Ca2＋ oscillations. The results show that the fraction of active phosphorylase is decreased with the total number of receptor channel IP3R increasing and for the small concentration of IP3 with appearance of coherence resonance.