The total concn. of MAPK is 300nM from Kholodenko, 2000.
6000.0
ee
0.005
5.0
CubeMesh
False
The total concn. of MAPK is 300nM from Kholodenko, 2000.
0.0
50.0
35
yellow
0.0
0.0
The total concn. of MKKK is 100nM from Kholodenko, 2000
0.0
650.0
16
yellow
0.0
0.0
The total concn. of MKK is 300nM from Kholodenko,2000
0.0
350.0
60
yellow
0.0
0.0
This is the intermediate enzyme which catalyses the dephosphorylation of MKKK-P to MKKK. The concentration is set to 1 nM based on from Kholodenko, 2000
210.52631578947367
600.0
30
yellow
0.0
0.0
This is the phosphorylated form of MKKK which converts MKK to MKK-P and then to MKK-PP from Kholodenko, 2000.
421.05263157894734
650.0
51
yellow
0.0
0.0
This intermediate enzyme catalyses the dephosphorylation of MKK-P to MKK. The concentration is 1nM from Kholodenko, 2000
210.52631578947367
300.0
blue
yellow
0.0
0.0
This catalyses the conversion of MAPK-P to MAPK. The concenration is 1nM. from Kholodenko, 2000
210.52631578947367
0.0
1
yellow
0.0
0.0
This is the single phoshorylated form of MKK. from Kholodenko, 2000.
421.05263157894734
350.0
5
yellow
0.0
0.0
This is the single phopshorylated form of MAPK from Kholodenko, 2000.
421.05263157894734
50.0
55
yellow
0.0
0.0
This intermediate enzyme which catalyses the dephosphorylation of MKK-PP to MKK-P. The concentration is 1nM. from Kholodenko, 2000
631.578947368421
300.0
2
yellow
0.0
0.0
This intermediate enzyme catalyses the dephosphorylation of MAPK-PP to MAPK-P. The concentration is 1nM. from Kholodenko, 2000
631.578947368421
0.0
17
yellow
0.0
0.0
The concn. of Ras-MKKKK* is set to 1 nM implicitly from Kholodenko, 2000
736.8421052631578
800.0
47
yellow
0.0
0.0
This is the inactive form of Ras-MKKK. Based on the reaction scheme from Kholodenko 2000, this is equivalent to a binding of the MAPK-PP to the Ras. The amount of Ras in the model is small enough that negligible amounts of MAPK are involved in this reaction. So it is a fair approximation to the negative feedback mechanism from Kholodenko, 2000.
1000.0
800.0
30
yellow
0.0
0.0
This is the double phosphorylated and active form of MKK from Kholodenko, 2000
842.1052631578947
350.0
60
yellow
0.0
0.0
This is the double phosphorylated and active form of MAPK. from Kholodenko, 2000.
842.1052631578947
50.0
46
yellow
0.0
0.0
Km is 8nM and Vmax is 0.25nM.s-1 from Kholodenko, 2000.
210.52631578947367
650.0
red
30
kinetics_1962_0_ * ( kcat * MKKK_P_1981_0_ * int1_1977_0_/(Km + MKKK_P_1981_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKKK\_P\_1981\_0\_}\mathrm{int1\_1977\_0\_}}{\mathrm{Km}+\mathrm{MKKK\_P\_1981\_0\_}}$
Km is 15 nM and Vmax is 0.025s-1 from Kholodenko, 2000
210.52631578947367
500.0
red
51
kinetics_1962_0_ * ( kcat * MKK_1975_0_ * MKKK_P_1981_0_/(Km + MKK_1975_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKK\_1975\_0\_}\mathrm{MKKK\_P\_1981\_0\_}}{\mathrm{Km}+\mathrm{MKK\_1975\_0\_}}$
Km is 15nM and Vmax is 0.025s-1 from Kholodenko, 2000.
631.578947368421
500.0
red
51
kinetics_1962_0_ * ( kcat * MKK_P_1995_0_ * MKKK_P_1981_0_/(Km + MKK_P_1995_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKK\_P\_1995\_0\_}\mathrm{MKKK\_P\_1981\_0\_}}{\mathrm{Km}+\mathrm{MKK\_P\_1995\_0\_}}$
The Km is 15nM and the Vmax is 0.75nM.s-1 from Kholodenko 2000.
210.52631578947367
350.0
red
blue
kinetics_1962_0_ * ( kcat * MKK_P_1995_0_ * int3_1987_0_/(Km + MKK_P_1995_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKK\_P\_1995\_0\_}\mathrm{int3\_1987\_0\_}}{\mathrm{Km}+\mathrm{MKK\_P\_1995\_0\_}}$
The Km is 15nM and Vmax is 0.5nM.s-1 from Kholodenko, 2000
210.52631578947367
50.0
red
1
kinetics_1962_0_ * ( kcat * MAPK_P_1997_0_ * int5_1991_0_/(Km + MAPK_P_1997_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MAPK\_P\_1997\_0\_}\mathrm{int5\_1991\_0\_}}{\mathrm{Km}+\mathrm{MAPK\_P\_1997\_0\_}}$
The Km is 15nM and Vmax is 0.75nM.s-1 from Kholodenko, 2000
631.578947368421
350.0
red
2
kinetics_1962_0_ * ( kcat * MKK_PP_2015_0_ * int2_1999_0_/(Km + MKK_PP_2015_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKK\_PP\_2015\_0\_}\mathrm{int2\_1999\_0\_}}{\mathrm{Km}+\mathrm{MKK\_PP\_2015\_0\_}}$
The Km is 15nM and Vmax is 0.5nM.s-1 from Kholodenko, 2000
631.578947368421
50.0
red
17
kinetics_1962_0_ * ( kcat * MAPK_PP_2021_0_ * int4_2003_0_/(Km + MAPK_PP_2021_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MAPK\_PP\_2021\_0\_}\mathrm{int4\_2003\_0\_}}{\mathrm{Km}+\mathrm{MAPK\_PP\_2021\_0\_}}$
The Km is 10nM and Vmax is 2.5nM sec^-1. We assume that there is 1 nM of the Ras-MKKKK. From Kholodenko, 2000. If the enzymes are not flagged as Available, then this Km should be set to 0.1 to obtain oscillations.
210.52631578947367
800.0
red
47
kinetics_1962_0_ * ( kcat * MKKK_1973_0_ * Ras_MKKKK_2007_0_/(Km + MKKK_1973_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MKKK\_1973\_0\_}\mathrm{Ras\_MKKKK\_2007\_0\_}}{\mathrm{Km}+\mathrm{MKKK\_1973\_0\_}}$
The Km is 15nM which is 0.015uM Vmax is 0.025s-1 from Kholodenko, 2000.
210.52631578947367
200.0
red
60
kinetics_1962_0_ * ( kcat * MAPK_1971_0_ * MKK_PP_2015_0_/(Km + MAPK_1971_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MAPK\_1971\_0\_}\mathrm{MKK\_PP\_2015\_0\_}}{\mathrm{Km}+\mathrm{MAPK\_1971\_0\_}}$
The Km is 15nM which is 0.015uM and Vmax is 0.025s-1 from Kholodenko, 2000
631.578947368421
200.0
red
60
kinetics_1962_0_ * ( kcat * MAPK_P_1997_0_ * MKK_PP_2015_0_/(Km + MAPK_P_1997_0_))
$\mathrm{kinetics\_1962\_0\_}\frac{\mathrm{kcat}\mathrm{MAPK\_P\_1997\_0\_}\mathrm{MKK\_PP\_2015\_0\_}}{\mathrm{Km}+\mathrm{MAPK\_P\_1997\_0\_}}$
kinetics_1962_0_
kinetics_1962_0_
#FFFF00
This is the oscillatory MAPK model from Kholodenko 2000 Eur J. Biochem 267:1583-1588 The original model is formulated in terms of idealized Michaelis-Menten enzymes and the enzyme-substrate complex concentrations are therefore assumed negligible. The current implementation of the model uses explicit enzyme reactions involving substrates and is therefore an approximation to the Kholodenko model. The approximation is greatly improved if the enzyme is flagged as Available which is an option in Kinetikit. This flag means that the enzyme protein concentration is not reduced even when it is involved in a complex. However, the substrate protein continues to participate in enzyme-substrate complexes and its concentration is therefore affected. Overall, this model works almost the same as the Kholodenko model but the peak MAPK-PP amplitudes are a little reduced and the period of oscillations is about 10% longer. If the enzymes are not flagged as Available then the oscillations commence only when the Km for enzyme 1 is set to 0.1 uM.