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achcar2

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AKc

{2.0}ADPc = AMPc + ATPc

AKg

{44.5116}ADPg = {22.2558}AMPg + {22.2558}ATPg

ALDg

{22.2558}Fru16BPg = {22.2558}DHAPg + {22.2558}GA3Pg

ATPuc

ATPc = ADPc

DHAPtg

DHAPc = {22.2558}DHAPg

ENOc

PGA2c = PEPc

G3PDHg

{22.2558}DHAPg + {22.2558}NADHg = {22.2558}Gly3Pg + {22.2558}NADg

GAPDHg

Pig + {22.2558}GA3Pg + {22.2558}NADg = {22.2558}BPGA13g + {22.2558}NADHg

GKg

{22.2558}ADPg + {22.2558}Gly3Pg = {22.2558}ATPg + {22.2558}Glyg

GPOc

Gly3Pc = DHAPc

GlcTc

Glce = Glcc

GlcTg

Glcc = {22.2558}Glcg

Gly3Ptg

{22.2558}Gly3Pg = Gly3Pc

GlyTc

Glyc = Glye

Glytg

{22.2558}Glyg = Glyc

HXKg

{22.2558}ATPg + {22.2558}Glcg = {22.2558}ADPg + {22.2558}Glc6Pg

PFKg

{22.2558}ATPg + {22.2558}Fru6Pg = {22.2558}ADPg + {22.2558}Fru16BPg

PGA3Tg

{22.2558}PGA3g = PGA3c

PGAMc

PGA3c = PGA2c

PGIg

{22.2558}Glc6Pg = {22.2558}Fru6Pg

PGKg

{22.2558}BPGA13g + {22.2558}ADPg = {22.2558}PGA3g + {22.2558}ATPg

PYKc

ADPc + PEPc = ATPc + Pyrc

PyrTc

Pyrc = Pyre

TPIg

{22.2558}DHAPg = {22.2558}GA3Pg

Parameters

Global parameters

AKcAKck1*

AKcAKck2*

AKgAKgk1*

AKgAKgk2*

ALDgALDgKeq*

ALDgALDgKiADP*

ALDgALDgKiAMP*

ALDgALDgKiATP*

ALDgALDgKiGA3P*

ALDgALDgKmDHAP*

ALDgALDgKmFru16BP*

ALDgALDgKmGA3P*

ALDgALDgVmax*

ATPucATPuck*

DHAPtgDHAPtgk*

ENOcENOcKeq*

ENOcENOcKmPEP*

ENOcENOcKmPGA2*

ENOcENOcVmax*

EXTERNAL*

G3PDHgG3PDHgKeq*

G3PDHgG3PDHgKmDHAP*

G3PDHgG3PDHgKmGly3P*

G3PDHgG3PDHgKmNAD*

G3PDHgG3PDHgKmNADH*

G3PDHgG3PDHgVmax*

GAPDHgGAPDHgKeq*

GAPDHgGAPDHgKmBPGA13*

GAPDHgGAPDHgKmGA3P*

GAPDHgGAPDHgKmNAD*

GAPDHgGAPDHgKmNADH*

GAPDHgGAPDHgVmax*

GKgGKgKeq*

GKgGKgKmADP*

GKgGKgKmATP*

GKgGKgKmGly*

GKgGKgKmGly3P*

GKgGKgVmax*

GPOcGPOcKiSHAM*

GPOcGPOcKmGly3P*

GPOcGPOcVmax*

GlcTcGlcTcKmGlc*

GlcTcGlcTcVmax*

GlcTcGlcTcalpha*

GlcTgGlcTgk*

Gly3PtgGly3Ptgk*

GlyTcGlyTcKmGlye*

GlyTcGlyTcVrmax*

GlyTcGlyTck*

GlyTcGlyTcx*

GlyTcGlyTcy*

GlytgGlytgk*

HXKgHXKgKeq*

HXKgHXKgKmADP*

HXKgHXKgKmATP*

HXKgHXKgKmGlc*

HXKgHXKgKmGlc6P*

HXKgHXKgVmax*

O2c*

PFKgPFKgKeq*

PFKgPFKgKi1*

PFKgPFKgKi2*

PFKgPFKgKmADP*

PFKgPFKgKmATP*

PFKgPFKgKmFru6P*

PFKgPFKgKsATP*

PFKgPFKgVmax*

PGA3TgPGA3Tgk*

PGAMcPGAMcKeq*

PGAMcPGAMcKmPGA2*

PGAMcPGAMcKmPGA3*

PGAMcPGAMcVmax*

PGIgPGIgKeq*

PGIgPGIgKmFru6P*

PGIgPGIgKmGlc6P*

PGIgPGIgVmax*

PGKgPGKgKeq*

PGKgPGKgKmADP*

PGKgPGKgKmATP*

PGKgPGKgKmBPGA13*

PGKgPGKgKmPGA3*

PGKgPGKgVmax*

PYKcPYKcKeq*

PYKcPYKcKiADP*

PYKcPYKcKiATP*

PYKcPYKcKmADP*

PYKcPYKcKmATP*

PYKcPYKcKmPEP*

PYKcPYKcKmPyr*

PYKcPYKcVmax*

PYKcPYKcn*

PyrTcPyrTcKmPyr*

PyrTcPyrTcVmax*

SHAM*

TPIgTPIgKeq*

TPIgTPIgKmDHAP*

TPIgTPIgKmGA3P*

TPIgTPIgVmax*

cytosol*

default*

glycosome*

default_compartment*

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

Explicit consideration of topological and parameter uncertainty gives new insights into a well-established model of glycolysis.

Fiona Achcar
Michael P Barrett
Rainer Breitling

FEBS J. 2013; 280 (18): 4640-4651

PubMed: 23865459
PubMed Central: PMC4768353
DOI: 10.1111/febs.12436
ISSN: 1742-4658
URL: http://ncbi.nlm.nih.gov/pubmed/23865459

Abstract

Previous models of glycolysis in the sleeping sickness parasite Trypanosoma brucei assumed that the core part of glycolysis in this unicellular parasite is tightly compartimentalized within an organelle, the glycosome, which had previously been shown to contain most of the glycolytic enzymes. The glycosomes were assumed to be largely impermeable, and exchange of metabolites between the cytosol and the glycosome was assumed to be regulated by specific transporters in the glycosomal membrane. This tight compartmentalization was considered to be essential for parasite viability. Recently, size-specific metabolite pores were discovered in the membrane of glycosomes. These channels are proposed to allow smaller metabolites to diffuse across the membrane but not larger ones. In light of this new finding, we re-analyzed the model taking into account uncertainty about the topology of the metabolic system in T. brucei, as well as uncertainty about the values of all parameters of individual enzymatic reactions. Our analysis shows that these newly-discovered nonspecific pores are not necessarily incompatible with our current knowledge of the glycosomal metabolic system, provided that the known cytosolic activities of the glycosomal enzymes play an important role in the regulation of glycolytic fluxes and the concentration of metabolic intermediates of the pathway.

No additional notes are available for this model.

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