研究经典酶动力学方程在细胞内小区室中的稳健性
Investigating the robustness of the classical enzyme kinetic equations in small intracellular compartments
摘要：
酶动力学的经典描述忽略了细胞内环境的物理性质。这些方法背后的主要隐含假设是反应发生在足够大的隔室体积中，使得分子离散性可以忽略，并且分子运输通过扩散发生。从酶反应动力学的主方程描述和假设代谢稳态条件开始，我们推导出新的介观速率方程，该方程考虑到（i）由于细胞内室中分子的低拷贝数而引起的固有分子噪声（ii）底物运输过程的物理性质，即扩散或囊泡介导的运输。这些方程取代了传统的宏观和确定性的细胞内动力学方程。后者在无限隔室体积的限制下回收。我们发现，偏离经典动力学的预测是明显的（百分之几百的反应速度的估计）酶反应发生在车厢是小于约200 nm的情况下，基板运输到车厢主要介导的囊泡或颗粒运输和竞争性酶抑制剂的存在下。这对使用常微分方程模拟大型细胞内反应网络的常用方法以及计算竞争性抑制剂药物的有效剂量具有影响。
英文摘要：
Classical descriptions of enzyme kinetics ignore the physical nature of the intracellular environment. Main implicit assumptions behind such approaches are that reactions occur in compartment volumes which are large enough so that molecular discreteness can be ignored and that molecular transport occurs via diffusion. Starting from a master equation description of enzyme reaction kinetics and assuming metabolic steady-state conditions, we derive novel mesoscopic rate equations which take into account (i) the intrinsic molecular noise due to the low copy number of molecules in intracellular compartments (ii) the physical nature of the substrate transport process, i.e. diffusion or vesicle-mediated transport. These equations replace the conventional macroscopic and deterministic equations in the context of intracellular kinetics. The latter are recovered in the limit of infinite compartment volumes. We find that deviations from the predictions of classical kinetics are pronounced (hundreds of percent in the estimate for the reaction velocity) for enzyme reactions occurring in compartments which are smaller than approximately 200nm, for the case of substrate transport to the compartment being mediated principally by vesicle or granule transport and in the presence of competitive enzyme inhibitors. This has implications for the common approach of modelling large intracellular reaction networks using ordinary differential equations and also for the calculation of the effective dosage of competitive inhibitor drugs.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
