The Alarm Mechanism Of Glycolysis Under Stress

Some organisms can produce oscillations including damped oscillations under certain pressure, such as the lack of cell glucose induced oscillation of ATP concentration, cell membrane potential oscillations induced by hypoxia, P53 concentration oscillation induced by DNA damage. These are the responses of cells to stress, and the generation of these oscillations is to transmit a signal. But the organism is how to design the alarm mechanism makes the oscillation signal better? In this paper, we take the myocardial ischemia of blood glucose as an example, in which a mathematical model is established and the sensitivity of feedback control theory is used to study the above problems.The following are our main results and contribution:(1) Previous studies of glycolysis are emphasized from steady state to the bifurcation oscillation, but the experimental result is that the attenuation of the oscillation is not the true oscillation. In this paper, this kind of condition is considered as a sensitive reaction from one steady state to another in the process of jumping.(2) Through the control theory analysis model we can obtain the related analytic expression: weighted sensitivity function, sensitivity function, weight function, the open-loop transfer function.(3) Based on the analytic formula of the sensitivity function and the weighted sensitivity function, in the F6P-FBP model, the parameters affect the peak value of the sensitivity function and the weighted sensitivity function. We take c, b, n, Vs, Kd with different values and first fixed four parameter values, we found that with the change of the parameter value, the peak value of the sensitivity function and the weighted sensitivity function have a certain change tendency, and the higher the sensitivity of the parameters, the bigger the peak value of the sensitivity function and the weighted sensitivity function.(4) In the F6P-FBP model, the sensitivity of the parameter region is related to the peak value of the weighted sensitivity function. The different values of c, b, n and Kd were obtained respectively, and the sensitive parameter region was found to correspond to the peak value of the weighted sensitivity function. Therefore, the sensitive parameter region can be found directly by the method of weighted sensitivity function. According to this method to explore the sensitive areas of different parameters, parameter values and parameter sensitive region that has changed a certain relationship. It can choose the appropriate parameters so that the system can produce a better oscillation signal under external pressure.To summarize the results of the study we found in biology has a corresponding relationship, such as the hill constants, feedback control coefficient, changes in transcription rate, degradation rate, sensitivity of the organism and sensitive parameter region has certain change trend. It can be seen that biology does conform to the above theoretical analysis to design the alarm mechanism.