Hynne F, Danø S, Sørensen P G
Department of Chemistry and CATS, H.C. Ørsted Institute, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
Biophys Chem. 2001 Dec 11;94(1-2):121-63. doi: 10.1016/s0301-4622(01)00229-0.
We present a powerful, general method of fitting a model of a biochemical pathway to experimental substrate concentrations and dynamical properties measured at a stationary state, when the mechanism is largely known but kinetic parameters are lacking. Rate constants and maximum velocities are calculated from the experimental data by simple algebra without integration of kinetic equations. Using this direct approach, we fit a comprehensive model of glycolysis and glycolytic oscillations in intact yeast cells to data measured on a suspension of living cells of Saccharomyces cerevisiae near a Hopf bifurcation, and to a large set of stationary concentrations and other data estimated from comparable batch experiments. The resulting model agrees with almost all experimentally known stationary concentrations and metabolic fluxes, with the frequency of oscillation and with the majority of other experimentally known kinetic and dynamical variables. The functional forms of the rate equations have not been optimized.
我们提出了一种强大的通用方法，用于在机制大致已知但缺乏动力学参数的情况下，将生化途径模型与在稳态下测量的实验底物浓度和动力学特性进行拟合。通过简单的代数运算从实验数据中计算速率常数和最大速度，而无需对动力学方程进行积分。使用这种直接方法，我们将完整酵母细胞中糖酵解和糖酵解振荡的综合模型与在酿酒酵母活细胞悬浮液中接近霍普夫分岔处测量的数据，以及从可比分批实验估计的大量稳态浓度和其他数据进行拟合。所得模型与几乎所有实验已知的稳态浓度和代谢通量、振荡频率以及大多数其他实验已知的动力学和动态变量相符。速率方程的函数形式并未进行优化。
