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).