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vanniekerk1

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vPFvALD

f16bpPF = gapPF + dhapPF

vPFvATPASE

atpPF = adpPF

vPFvENO

p2gPF = pepPF

vPFvG3PDH

dhapPF + nadhPF = nadPF + g3pPF

vPFvGAPDH

nadPF + gapPF = nadhPF + b13pgPF

vPFvGLCtr

glcEX = glcPF

vPFvGLYtr

g3pPF = glyEX

vPFvHK

glcPF + atpPF = g6pPF + adpPF

vPFvLACtr

lacPF = lacEX

vPFvLDH

pyrPF + nadhPF = nadPF + lacPF

vPFvPFK

f6pPF + atpPF = f16bpPF + adpPF

vPFvPGI

g6pPF = f6pPF

vPFvPGK

b13pgPF + adpPF = p3gPF + atpPF

vPFvPGM

p3gPF = p2gPF

vPFvPK

pepPF + adpPF = pyrPF + atpPF

vPFvPYRtr

pyrPF = pyrEX

vPFvTPI

dhapPF = gapPF

Parameters

Global parameters

ConcAdpPF*

ConcAtpPF*

ConcB13pgPF*

ConcDhapPF*

ConcF16bpPF*

ConcF6pPF*

ConcG6pPF*

ConcGapPF*

ConcGlcEX*

ConcGlcPF*

ConcGly3pPF*

ConcGlyEX*

ConcLacEX*

ConcLacPF*

ConcNadPF*

ConcNadhPF*

ConcP2gPF*

ConcP3gPF*

ConcPepPF*

ConcPyrEX*

ConcPyrPF*

KPFvGLCtr*

KadpPFvHK*

KadpPFvPFK*

KadpPFvPGK*

KadpPFvPK*

KatpPFvHK*

KatpPFvPFK*

KatpPFvPGK*

Kb13pgPFvGAPDH*

Kb13pgPFvPGK*

KdPFvLACtr*

KdPFvPYRtr*

KdhapPFvALD*

KdhapPFvG3PDH*

KdhapPFvTPI*

KeqPFvALD*

KeqPFvENO*

KeqPFvG3PDH*

KeqPFvHK*

KeqPFvPGI*

KeqPFvPGK*

KeqPFvPGM*

KeqPFvTPI*

Kf16bpPFvALD*

Kf16bpPFvPFK*

Kf6pPFvPFK*

Kf6pPFvPGI*

Kg3pPFvG3PDH*

Kg6pPFvHK*

Kg6pPFvPGI*

KgapPFvALD*

KgapPFvGAPDH*

KgapPFvTPI*

KglcPFvHK*

Ki1CytGlcTr*

Ki2CytGlcTr*

KiadpPFvPK*

KiatpPFvHK*

KiatpPFvPK*

KilacPFvPYRtr*

KipepPFvPK*

KipepPFvTPI*

KipyrPFvLACtr*

KipyrPFvPK*

KlacPFvLACtr*

KlacPFvLDH*

KmPFvATPASE*

KnadPFvG3PDH*

KnadPFvGAPDH*

KnadPFvLDH*

KnadhPFvG3PDH*

KnadhPFvGAPDH*

KnadhPFvLDH*

Kp2gPFvENO*

Kp2gPFvPGM*

Kp3gPFvPGK*

Kp3gPFvPGM*

KpepPFvENO*

KpepPFvPK*

KpyrPFvLDH*

KpyrPFvPYRtr*

LPFvPK*

VPFvALD*

VPFvATPASE*

VPFvENO*

VPFvGAPDH*

VPFvGLCtr*

VPFvHK*

VPFvLACtr*

VPFvPFK*

VPFvPGI*

VPFvPGM*

VPFvPK*

VPFvPYRtr*

VPFvTPI*

VfPFvG3PDH*

VfPFvLDH*

VrPFvGAPDH*

VrPFvLDH*

VrPFvPGK*

alphaPFvGLCtr*

cytb*

kPFvGLYtr*

pHConversionFactor*

phEX*

phPF*

Vex*

Vpf*

Functions and Rules

Assignment rules

hEX = pHConversionFactor / pow(10, phEX)

hPF = pHConversionFactor / pow(10, phPF)

Function definitions

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.

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Species

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Assignment rules

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Species

Rates

Assignment rules

Targeting glycolysis in the malaria parasite Plasmodium falciparum.

David D van Niekerk
Gerald P Penkler
Francois du Toit
Jacky L Snoep

FEBS J. 2016; 283 (4): 634-646

PubMed: 26648082
DOI: 10.1111/febs.13615
ISSN: 1742-4658
URL: http://ncbi.nlm.nih.gov/pubmed/26648082

Abstract

UNLABELLED: Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand.
DATABASE: The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.bio.vu.nl/database/vanniekerk1. The SEEK-study including the experimental data set is available at DOI 10.15490/seek.1.
INVESTIGATION: 56).

No additional notes are available for this model.

JWS Online documentation

vanniekerk1

Reactions

vPFvALD

vPFvATPASE

vPFvENO

vPFvG3PDH

vPFvGAPDH

vPFvGLCtr

vPFvGLYtr

vPFvHK

vPFvLACtr

vPFvLDH

vPFvPFK

vPFvPGI

vPFvPGK

vPFvPGM

vPFvPK

vPFvPYRtr

vPFvTPI

Parameters

Fixed species

Initial values

Functions and Rules

Assignment rules

Function definitions

Events

Constraints

Targeting glycolysis in the malaria parasite Plasmodium falciparum.

Abstract