Table 3.
Dynamic variables and constants of basal cyclic nucleotide signaling.
| 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 | [17-19] |
| 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] |
Description of the model parameters and constants of the formalized the system of ODEs modeling the basal cyclic nucleotide signaling (see Appendix).