Skip to main content

Advertisement

Table 3 Dynamic variables and constants of basal cyclic nucleotide signaling.

From: Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation

Model parameter Values Foundations/assumptions Reference
Dynamic variables    
x1: c(cAMP) 4 μM Basal levels [14]
x2:c(cGMP) 0.4 μM Basal levels [14]
x3:c(PDE2) active 0.05 mg/l Model-based simulation This study
   Experimentally: 63.46 mg/l  
x4:c(PDE3) active 2.3 mg/l Model-based simulation This study
   Experimentally: 225 mg/l  
x5:c(PDE5) active 1 mg/l Model-based simulation This study
   Experimentally: 1359 mg/l  
x6:c(PDE2) inactive (63.46 -x3) mg/l   
x7:c(PDE3) inactive (225 - x4) mg/l   
x8:c(PDE5) inactive (1359 - x5) mg/l   
x9:c(AMP) μM; simulated   
x10:c(GMP) μM; simulated   
Constants    
k1: Vmax PDE2 120 μmol/min/mg cAMP turnover [2, 16]
k2:Km PDE2 50 μM cAMP turnover [2, 16]
k3:Vmax PDE3 3 μmol/min/mg cAMP turnover [2, 16]
k4:Km PDE3 0.2 μM cAMP turnover [2, 16]
k5:Vmax PDE2 120 μmol/min/mg cGMP turnover [2, 16]
k6:Km PDE2 35 μM cGMP turnover [2, 16]
k7:Vmax PDE3 0.3 μmol/min/mg cGMP turnover [2, 16]
k8:Km PDE3 0.02 μM cGMP turnover [2, 16]
k9:Vmax PDE5 5 μmol/min/mg cGMP turnover [2, 16]
k10:Km PDE5 5 μM cGMP turnover [2, 16]
k11:kcAMP 8 μmol/min Basal influx of cAMP [1719]
k12:kcGMP 1 μmol/min Basal influx of cGMP [64, 65]
k13:Deactivation PDE2    This study
k14:Activation PDE2 k13-k18: = 0   This study
k15:Deactivation PDE3 for simulation of   This study
k16:Activation PDE3 basal levels   This study
k17:Deactivation PDE5 (resting conditions)   This study
k18:Activation PDE5    This study
k19:hPDE2 2 Hill coefficient [15, 16]
  1. Description of the model parameters and constants of the formalized the system of ODEs modeling the basal cyclic nucleotide signaling (see Appendix).