JWS Online

vanHeerden1

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v1

GLCi + Prb = G6P

v10

P2G = PEP

v11

PEP = Prb + PYR

v12

PYR = ACE + CO2

v13

{2.0}ACE + {3.0}NAD = SUCC + {3.0}NADH

v14

GLCo = GLCi

v15

ACE + NADH = ETOH + NAD

v16

NADH + TRIO = PHOS + GLY + NAD

v17

Prb = PHOS

v18

X = PHOS

v2

G6P = F6P

v3

G6P + Prb = Glyc + {2.0}PHOS

v4

Prb + {2.0}G6P = Trh + {3.0}PHOS

v5

F6P + Prb = F16P

v6

F16P = {2.0}TRIO

v7

PHOS + TRIO + NAD = BPG + NADH

v8

BPG = P3G + Prb

v9

P3G = P2G

Parameters

Global parameters

CPFKAMP*

CPFKATP*

CPFKF16BP*

CPFKF26BP*

CPFKF6P*

CiPFKATP*

F26BP*

KATPASE*

KEQAK*

KEQHK*

KMHKADP*

KMHKATP*

KMHKG6P*

KMHKGLCi*

KPFKAMP*

KPFKF16BP*

KPFKF26BP*

KPHOS*

KSUCC*

KTREHALOSE*

KeqADH*

KeqAK*

KeqALD*

KeqENO*

KeqG3PDH*

KeqGLT*

KeqPGI*

KeqPGK*

KeqPGM*

KeqPYK*

KeqTPI*

KiADHACE*

KiADHETOH*

KiADHNAD*

KiADHNADH*

KiHKG6P*

KiPFKATP*

KmADHACE*

KmADHETOH*

KmADHNAD*

KmADHNADH*

KmALDDHAP*

KmALDF16P*

KmALDGAP*

KmALDGAPi*

KmENOP2G*

KmENOPEP*

KmG3PDHDHAP*

KmG3PDHGLY*

KmG3PDHNAD*

KmG3PDHNADH*

KmGAPDHBPG*

KmGAPDHGAP*

KmGAPDHNAD*

KmGAPDHNADH*

KmGLTGLCi*

KmGLTGLCo*

KmGLYCOGEN*

KmPDCPYR*

KmPFKATP*

KmPFKF6P*

KmPGIF6P*

KmPGIG6P*

KmPGKADP*

KmPGKATP*

KmPGKBPG*

KmPGKP3G*

KmPGMP2G*

KmPGMP3G*

KmPYKADP*

KmPYKATP*

KmPYKF16P*

KmPYKPEP*

L0*

L0PYK*

NADt*

SUMAXP*

VMAXHK*

VmADH*

VmALD*

VmENO*

VmG3PDH*

VmGAPDHf*

VmGAPDHr*

VmGLT*

VmPDC*

VmPFK*

VmPGI*

VmPGK*

VmPGM*

VmPYK*

gR*

nPDC*

npyk*

pT*

wt*

compartment*

Functions and Rules

Assignment rules

ATP = (-SUMAXP + (1.0 - 4.0 * KEQAK) * Prb + pow(4.0 * (1.0 - 4.0 * KEQAK) * KEQAK * pow(Prb, 2.0) + pow(SUMAXP - (1.0 - 4.0 * KEQAK) * Prb, 2.0), 0.5)) / (2.0 * (1.0 - 4.0 * KEQAK))

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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Show modifiers*

Show compartments*

Gravity*

Repulsion*

Pool threshold*

Species:

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Model schema*

Parameter*

Start*

End*

Steps*

Species

Rates

Assignment rules

Lost in transition: start-up of glycolysis yields subpopulations of nongrowing cells.

Johan H van Heerden
Meike T Wortel
Frank J Bruggeman
Joseph J Heijnen
Yves J M Bollen
Robert Planqué
Josephus Hulshof
Tom G O'Toole
S Aljoscha Wahl
Bas Teusink

Science 2014; 343 (6174): 1245114

PubMed: 24436182
DOI: 10.1126/science.1245114
ISSN: 1095-9203
URL: https://ncbi.nlm.nih.gov/pubmed/24436182

Abstract

Cells need to adapt to dynamic environments. Yeast that fail to cope with dynamic changes in the abundance of glucose can undergo growth arrest. We show that this failure is caused by imbalanced reactions in glycolysis, the essential pathway in energy metabolism in most organisms. The imbalance arises largely from the fundamental design of glycolysis, making this state of glycolysis a generic risk. Cells with unbalanced glycolysis coexisted with vital cells. Spontaneous, nongenetic metabolic variability among individual cells determines which state is reached and, consequently, which cells survive. Transient ATP (adenosine 5'-triphosphate) hydrolysis through futile cycling reduces the probability of reaching the imbalanced state. Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.

This model reproduces Figure 1B of the paper.

JWS Online documentation

vanHeerden1

Reactions

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Parameters

Fixed species

Initial values

Functions and Rules

Assignment rules

Function definitions

Events

Constraints

Lost in transition: start-up of glycolysis yields subpopulations of nongrowing cells.

Abstract