Info! This is a derivative of the model dupreez2-user
 Edit

dupreez2

mmol

min

L

None

None

mM

From steady-state to synchronized yeast glycolytic oscillations I: model construction.

  • Franco B du Preez
  • David D van Niekerk
  • Bob Kooi
  • Johann M Rohwer
  • Jacky L Snoep
FEBS J. 2012; 279 (16): 2810-2822
Abstract
UNLABELLED: An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. Using a small subset of experimental data, the original model was adapted by adjusting its parameter values in three optimization steps. Only small adaptations to the original model were required for realistic simulation of experimental data for limit-cycle oscillations. The greatest changes were required for parameter values for the phosphofructokinase reaction. The importance of ATP for the oscillatory mechanism and NAD(H) for inter-and intra-cellular communications and synchronization was evident in the optimization steps and simulation experiments. In an accompanying paper [du Preez F et al. (2012) FEBS J279, 2823-2836], we validate the model for a wide variety of experiments on oscillatory yeast cells. The results are important for re-use of detailed kinetic models in modular modeling approaches and for approaches such as that used in the Silicon Cell initiative.
DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
60.0 second
0.001 mole
1.0 litre
0.001 mole litre^(-1.0)
Id Name Spatial dimensions Size
default_compartment 3.0 1.0 L
Id Name Initial quantity Compartment Fixed
ACE 0.0320190578411128 mmol/L default_compartment
ADP ADP <assignment rule> mmol/L default_compartment
AMP 0.169126793522056 mmol/L default_compartment
ATP 2.88896546881255 mmol/L default_compartment
BPG 0.000272378466415018 mmol/L default_compartment
F16P 5.12303060629701 mmol/L default_compartment
F6P 1.35316959717949 mmol/L default_compartment
G3P 1.51464838664408 mmol/L default_compartment
G6P 5.23300353550081 mmol/L default_compartment
GLCi 0.0264527982731908 mmol/L default_compartment
NAD NAD <assignment rule> mmol/L default_compartment
NADH 0.570243405517748 mmol/L default_compartment
P2G 0.0219411145027765 mmol/L default_compartment
P3G 0.182294273856502 mmol/L default_compartment
PEP 0.0180777173496713 mmol/L default_compartment
PYR 2.26719823411809 mmol/L default_compartment
TRIO 2.65068578040418 mmol/L default_compartment

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
v_ADH v_ADH ACE + NADH = ∅

-(VmADH * (ETOH * NAD - ACE * NADH / KeqADH) / (KiADHNAD * KmADHETOH * (1 + ETOH * KmADHNAD / (KiADHNAD * KmADHETOH) + KmADHNADH * ACE / (KiADHNADH * KmADHACE) + NAD / KiADHNAD + ETOH * NAD / (KiADHNAD * KmADHETOH) + ETOH * ACE * NAD / (KiADHACE * KiADHNAD * KmADHETOH) + KmADHNADH * ACE * NAD / (KiADHNAD * KiADHNADH * KmADHACE) + NADH / KiADHNADH + ETOH * KmADHNAD * NADH / (KiADHNAD * KiADHNADH * KmADHETOH) + ACE * NADH / (KiADHNADH * KmADHACE) + ETOH * ACE * NADH / (KiADHETOH * KiADHNADH * KmADHACE))))
v_AK v_AK ∅ = AMP + ATP

133.333 * (pow(ADP, 2) - AMP * ATP / KeqAK)
v_ALD F16P = {2.0}TRIO

VmALD * (F16P - KeqTPI * pow(TRIO, 2) / (KeqALD * pow(1 + KeqTPI, 2))) / (KmALDF16P * (1 + F16P / KmALDF16P + TRIO / ((1 + KeqTPI) * KmALDDHAP) + KeqTPI * TRIO / ((1 + KeqTPI) * KmALDGAP) + KeqTPI * F16P * TRIO / ((1 + KeqTPI) * KmALDF16P * KmALDGAPi) + KeqTPI * pow(TRIO, 2) / (pow(1 + KeqTPI, 2) * KmALDDHAP * KmALDGAP)))
v_ATP ATP = ∅

KATPASE * pow(ATP, nATP) / (pow(KmATP, nATP) + pow(ATP, nATP))
v_ENO P2G = PEP

VmENO * (P2G - PEP / KeqENO) / (KmENOP2G * (1 + P2G / KmENOP2G + PEP / KmENOPEP))
v_G3PA G3P = ∅

VmG3PA * G3P / (KmG3PAG3P * (1 + Phi / KmG3PAPhi) * (1 + G3P / KmG3PAG3P))
v_G3PDH v_G3PDH NADH + TRIO = G3P

VmG3PDH * (-(G3P * NAD / KeqG3PDH) + NADH * TRIO / (1 + KeqTPI)) / (KmG3PDHDHAP * KmG3PDHNADH * (1 + ADP / KmG3PDHADP + ATP / KmG3PDHATP + F16P / KmG3PDHF16P) * (1 + NAD / KmG3PDHNAD + NADH / KmG3PDHNADH) * (1 + G3P / KmG3PDHG3P + TRIO / ((1 + KeqTPI) * KmG3PDHDHAP)))
v_GAPDH v_GAPDH TRIO = BPG + NADH

(-(VmGAPDHf * BPG * NADH / (KeqGAPDH * KmGAPDHGAP * KmGAPDHNAD)) + KeqTPI * VmGAPDHf * NAD * TRIO / ((1 + KeqTPI) * KmGAPDHGAP * KmGAPDHNAD)) / ((1 + NAD / KmGAPDHNAD + NADH / KmGAPDHNADH) * (1 + BPG / KmGAPDHBPG + KeqTPI * TRIO / ((1 + KeqTPI) * KmGAPDHGAP)))
v_GLK v_GLK ATP + GLCi = G6P

VmGLK * (-(ADP * G6P / KeqGLK) + ATP * GLCi) / (KmGLKATP * KmGLKGLCi * (1 + ADP / KmGLKADP + ATP / KmGLKATP) * (1 + G6P / KmGLKG6P + GLCi / KmGLKGLCi))
v_GLT v_GLT ∅ = GLCi

VmGLT * (GLCo - GLCi / KeqGLT) / (KmGLTGLCo * (1 + GLCo / KmGLTGLCo + GLCi / KmGLTGLCi + alpha * GLCo * GLCi / (KmGLTGLCi * KmGLTGLCo)))
v_GLYCO ATP + G6P = ∅

KGLYCOGEN * ATP * G6P
v_PDC PYR = ACE

VmPDC * pow(PYR, nPDC) / (pow(KmPDCPYR, nPDC) * (1 + pow(PYR, nPDC) / pow(KmPDCPYR, nPDC)))
v_PFK ATP + F6P = F16P

gR * VmPFK * ATP * F6P * (1 + ATP / KmPFKATP + F6P / KmPFKF6P + gR * ATP * F6P / (KmPFKATP * KmPFKF6P)) / (KmPFKATP * KmPFKF6P * (L0 * pow(1 + CPFKAMP * AMP / KPFKAMP, 2) * pow(1 + CiPFKATP * ATP / KiPFKATP, 2) * pow(1 + CPFKATP * ATP / KmPFKATP, 2) * pow(1 + CPFKF26BP * F26BP / KPFKF26BP + CPFKF16BP * F16P / KPFKF16BP, 2) / (pow(1 + AMP / KPFKAMP, 2) * pow(1 + ATP / KiPFKATP, 2) * pow(1 + F26BP / KPFKF26BP + F16P / KPFKF16BP, 2)) + pow(1 + ATP / KmPFKATP + F6P / KmPFKF6P + gR * ATP * F6P / (KmPFKATP * KmPFKF6P), 2)))
v_PGI G6P = F6P

VmPGI * (-(F6P / KeqPGI) + G6P) / (KmPGIG6P * (1 + F6P / KmPGIF6P + G6P / KmPGIG6P))
v_PGK v_PGK BPG = ATP + P3G

VmPGK * (KeqPGK * ADP * BPG - ATP * P3G) / (KmPGKATP * KmPGKP3G * (1 + ADP / KmPGKADP + ATP / KmPGKATP) * (1 + BPG / KmPGKBPG + P3G / KmPGKP3G))
v_PGM P3G = P2G

VmPGM * (-(P2G / KeqPGM) + P3G) / (KmPGMP3G * (1 + P2G / KmPGMP2G + P3G / KmPGMP3G))
v_PYK v_PYK PEP = ATP + PYR

VmPYK * (ADP * PEP - ATP * PYR / KeqPYK) / (KmPYKADP * KmPYKPEP * (1 + ADP / KmPYKADP + ATP / KmPYKATP) * (1 + PEP / KmPYKPEP + PYR / KmPYKPYR))
v_SUC {2.0}ACE + {4.0}ATP = {3.0}NADH

KSUCC * ACE
v_Treha ATP + {2.0}G6P = ∅

KTREHALOSE * ATP * G6P

Global parameters

Id Value
AXPsum 4.1
CPFKAMP 0.0845
CPFKATP 3.0
CPFKF16BP 0.397
CPFKF26BP 0.0174
CiPFKATP 100.0
ETOH 50.0
EXTERNAL 0.0
F26BP 0.02
GLCo 10.0
KATPASE 68.809631749526
KGLYCOGEN 1.68983106019077
KPFKAMP 0.0995
KPFKF16BP 0.111
KPFKF26BP 0.000682
KSUCC 19.6023811745556
KTREHALOSE 0.754128480342013
KeqADH 0.000069
KeqAK 0.45
KeqALD 0.069
KeqENO 6.7
KeqG3PDH 4300.0
KeqGAPDH 0.00562639062770364
KeqGLK 3800.0
KeqGLT 1.0
KeqPGI 0.314
KeqPGK 3200.0
KeqPGM 0.19
KeqPYK 6500.0
KeqTPI 0.045
KiADHACE 1.1
KiADHETOH 90.0
KiADHNAD 0.92
KiADHNADH 0.031
KiPFKATP 0.65
KmADHACE 1.11
KmADHETOH 17.0
KmADHNAD 0.17
KmADHNADH 0.11
KmALDDHAP 2.4
KmALDF16P 0.3
KmALDGAP 2.0
KmALDGAPi 10.0
KmATP 0.263159506089159
KmENOP2G 0.04
KmENOPEP 0.5
KmG3PAG3P 4.21421727097407
KmG3PAPhi 0.798017147070638
KmG3PDHADP 1.60537927993171
KmG3PDHATP 0.568725492710765
KmG3PDHDHAP 0.4
KmG3PDHF16P 4.77110176421347
KmG3PDHG3P 1.088994646912
KmG3PDHNAD 0.93
KmG3PDHNADH 0.023
KmGAPDHBPG 0.0098
KmGAPDHGAP 0.21
KmGAPDHNAD 0.09
KmGAPDHNADH 0.06
KmGLKADP 0.23
KmGLKATP 0.15
KmGLKG6P 30.0
KmGLKGLCi 0.08
KmGLTGLCi 1.1918
KmGLTGLCo 1.1918
KmPDCPYR 4.33
KmPFKATP 0.71
KmPFKF6P 0.1
KmPGIF6P 0.3
KmPGIG6P 1.4
KmPGKADP 0.2
KmPGKATP 0.3
KmPGKBPG 0.003
KmPGKP3G 0.53
KmPGMP2G 0.08
KmPGMP3G 1.2
KmPYKADP 0.53
KmPYKATP 1.5
KmPYKPEP 0.14
KmPYKPYR 21.0
L0 0.66
NADSUM 1.0
Phi 1.20470265921072
VmADH 834.684820558968
VmALD 232.895576807474
VmENO 462.02518044535
VmG3PA 542.31923582697
VmG3PDH 477.924460922096
VmGAPDHf 419.560093466267
VmGLK 329.958304618391
VmGLT 136.494419254188
VmPDC 223.978775020613
VmPFK 183.616866462272
VmPGI 467.754325004144
VmPGK 1419.49486841362
VmPGM 2762.32037661175
VmPYK 1751.9596196023
alpha 0.91
gR 5.12
nATP 1.0
nPDC 1.9

Local parameters

Id Value Reaction

Assignment rules

Definition
NAD = NADSUM - NADH
ADP = AXPsum - AMP - ATP

Rate rules

Definition

Algebraic rules

Definition
Definition
Trigger Assignments