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notes: Achcar2012 - Glycolysis in bloodstream form T. brucei Kinetic models of metabolism require quantitative knowledge of detailed kinetic parameters. However, the knowledge about these parameters is often uncertain. An analysis of the effect of parameter uncertainties on a particularly well defined example of a quantitative metablic model, the model of glycolysis in bloodstream form Trypanosoma brucei , has been presented here. This model is described in the article: Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism. Achcar F, Kerkhoven EJ; SilicoTryp Consortium, Bakker BM, Barrett MP, Breitling R. PLoS Comput Biol. 2012 Jan; 8(1):e1002352. Abstract: Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of…
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845517
value: 250000.0
name: GlcT_g_k
type: LocalParameter

846465
value: 2.0
name: G3PDH_g_KmGly3P
type: LocalParameter

845613
stoichiometry: 1.0
species: 845145
type: SpeciesReference

844869
is version of: CHEBI:32816
constant: true
boundary condition: true
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: 844797
name: Pyr_e
type: Species

845865
value: 598.0
name: ENO_c_Vmax
type: LocalParameter

846105
modifier: 255989
fast: false
reactant: 846117
type: Reaction
modifier: 256025
product: 846153
modifier: 256013
reactant: 846129
modifier: 256001
is version of: GO:0004618
reversible: true
product: 846141
name: PGK_g
kinetic law: 846165

847425
stoichiometry: 1.0
species: 844857
type: SpeciesReference

846057
stoichiometry: 1.0
species: 845001
type: SpeciesReference

845049
is version of: CHEBI:26689
constant: true
boundary condition: true
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: 844797
name: O2_c
type: Species

846309
value: 0.185
name: PGAM_c_Keq
type: LocalParameter

845937
stoichiometry: 1.0
species: 845157
type: SpeciesReference

845433
value: 85.0
name: GlyT_c_Vmax
type: LocalParameter

845529
kinetic law: 845565
modifier: 255821
product: 845553
reactant: 845541
is version of: GO:0006848
fast: false
reversible: true
name: PyrT_c
type: Reaction

845349
value: 0.64
name: PYK_c_KiADP
type: LocalParameter

845133
is version of: CHEBI:17234
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.01
initial amount: NaN
in compartment: 844773
name: Glc_c
type: Species

847053
value: 0.4
name: PGI_g_KmGlc6P
type: LocalParameter

847473
is version of: GO:0004807
modifier: 256457
modifier: 256469
name: TPI_g
type: Reaction
reversible: true
fast: false
product: 847497
kinetic law: 847509
reactant: 847485

847137
stoichiometry: 1.0
species: 845121
type: SpeciesReference

846669
value: 0.44
name: GK_g_KmGly
type: LocalParameter

844917
is version of: CHEBI:17665
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.5
initial amount: NaN
in compartment: 844785
name: Glc6P_g
type: Species

847389
value: 600.0
name: GDA_g_k
type: LocalParameter

847221
value: 0.02
name: GAPDH_g_KmNADH
type: LocalParameter

847521
value: 999.3
name: TPI_g_Vmax
type: LocalParameter

846561
stoichiometry: 1.0
species: 845073
type: SpeciesReference

847161
value: 720.9
name: GAPDH_g_Vmax
type: LocalParameter

846045
modifier: 255977
name: _3PGAT_g
reversible: true
is version of: GO:0006810
type: Reaction
modifier: 255965
reactant: 846057
product: 846069
fast: false
kinetic law: 846081

844857
is version of: CHEBI:57642
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.23132912
initial amount: NaN
in compartment: 844773
name: DHAP_c
type: Species

846477
value: 0.4
name: G3PDH_g_KmNAD
type: LocalParameter

845769
value: 15.8
name: PFK_g_Ki1
type: LocalParameter

845925
stoichiometry: 1.0
species: 844821
type: SpeciesReference

845697
stoichiometry: 1.0
species: 844821
type: SpeciesReference

845625
stoichiometry: 1.0
species: 845133
type: SpeciesReference

847209
value: 0.1
name: GAPDH_g_Km13BPGA
type: LocalParameter

845145
is version of: CHEBI:17234
constant: true
boundary condition: true
has only substance units: false
initial concentration: 5.0
initial amount: NaN
in compartment: 844797
name: Glc_e
type: Species

847041
value: 0.3
name: PGI_g_Keq
type: LocalParameter

845445
value: 0.17
name: GlyT_c_KmGly
type: LocalParameter

845793
value: 0.026
name: PFK_g_KmATP
type: LocalParameter

847461
value: 1.7
name: GPO_c_KmGly3P
type: LocalParameter

846957
value: 442.0
name: AK_c_k1
type: LocalParameter

846657
value: 0.56
name: GK_g_KmADP
type: LocalParameter

844905
is version of: CHEBI:13389
constant: false
boundary condition: false
has only substance units: false
initial concentration: 2.0
initial amount: NaN
in compartment: 844785
name: NAD_g
type: Species

847233
modifier: 256385
is version of: GO:0004017
product: 847269
modifier: 256361
fast: false
product: 847257
reactant: 847245
reversible: true
modifier: 256373
kinetic law: 847281
type: Reaction
name: AK_g

846141
stoichiometry: 1.0
species: 845001
type: SpeciesReference

W3 CDTF: Tue Nov 20 18:36:29 GMT 2012

W3 CDTF: Mon Jun 10 14:41:07 BST 2013

given: Lukas
family: Endler

orgname: TBI

given: Vijayalakshmi
family: Chelliah

ORG:
  orgname: EMBL-EBI