doubts about reconstructions

Erlon Mendes

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Aug 17, 2011, 8:21:41 AM8/17/11

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Hi COBRA team,

After a lot of work, I can't find a way to make the Clostridium
acetobutylicum ATCC 824 grow. Yesterday, the situation became more
serious because I couldn't make the simple pathway presented in BOX3
be run in COBRA.

Reed, J.L., Famili, I., Thiele, I., and Palsson, B.Ø., "Towards
multidimensional genome annotation ", ",Nature Reviews Genetics, 7(2) :
130-41 (2006).

I read a lot about reconstructions but there is something that I am
missing. I'm sending the simple test that made me lost my faith.

reactions:
Rxn name Rxn description Formula Gene-reaction association Genes
Proteins Subsystem Reversible LB UB Objective
HEX1 HEX1 [c]GLC + ATP <=> G6P + ADP + H glk 1 -1000 1000 0
PGI PGI [c]G6P <=> F6P pgi 1 -1000 1000 0
PFK PFK [c]ATP + F6P -> ADP + FDP + H (pfkA and pfkB) 0 0 1000 0
FBA FBA [c]FDP <=> DHAP + G3P (fbaA and fbaB) 1 -1000 1000 0
TPI TPI [c]DHAP <=> G3P tpiA 1 -1000 1000 0
GAPD GAPD [c]G3P + NAD + PI <=> 13DPG + H + NADH (gapA and gapC1 and
gapC2) 1 -1000 1000 0
PGK PGK [c]13DPG + ADP <=> 3PG + ATP pgk 1 -1000 1000 0
GPM GPM [c]3PG <=> 2PG (gpmA and gpmB) 1 -1000 1000 0
ENO ENO [c]2PG <=> H2O + PEP eno 1 -1000 1000 0
PYK PYK [c]ADP + H + PEP -> ATP + PYR (pykA and pykF) 0 0 1000 1

metabolites:
Metabolite name Metabolite description Metabolite neutral formula
Metabolite charged formula Metabolite charge Metabolite Compartment
13DPG 0 cytosol
2PG 0 cytosol
3PG 0 cytosol
ADP 0 cytosol
ATP 0 cytosol
DHAP 0 cytosol
F6P 0 cytosol
FDP 0 cytosol
G3P 0 cytosol
G6P 0 cytosol
GLC 0 cytosol
H 0 cytosol
H2O 0 cytosol
NAD 0 cytosol
NADH 0 cytosol
PEP 0 cytosol
PI 0 cytosol
PYR 0 cytosol

You can see that I put all metabolite's charges as "0". This could be
the problem? The COBRA Toolbox uses the metabolite's charge like
motive force to reactions happen?

I put all reactions of the paper below in a xls model of Clostridium
(impossible to attach), but no glucose is consumed and no biomass is
formed. I have the metabolite's charges to put yet and to investigate
gaps on the original reactions in the paper. But I need to make a
simple model work (like the above) to learn how to do it.

Lee J, Yun H, Feist AM, Palsson BO, Lee SY (2008) Genome-scale
reconstruction and in silico analysis of the Clostridium
acetobutylicum ATCC824 metabolic network. Appl Microbiol Biotechnol 80
(5):849-862

My thesis is based on this subject and the time is running out.
Please, help me.

Best wishes,

Erlon Mendes

Ines Thiele

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Aug 17, 2011, 8:42:47 AM8/17/11

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Dear Erlon

the reaction pathway as you listed it in your email does indeed not
work. The reason is that you did not define the boundary conditions
(e.g., exchange reactions or at least demand/sink reactions). This is
necessary as we model under steady-state assumptions, meaning that
there is no accumulation of metabolites allowed within the network.
Exchange and demand/sink reactions allows us to represent accumulation
or metabolite consumption from nothing thus converting a closed system
(as you listed below) into an open system. Such setup therefore
permits flux through the network reactions (where sum of influxes
equals sum of outfluxes and thus being consistent with steady-state),
while permitting the usage or accumulation of a defined set of
metabolites.

There is a growing body of literature available explaining these
modeling principles. I recommend
- Palsson, Systems Biology: Properties of Reconstructed Networks
- Thiele, I. and Palsson, B. O.,"''A protocol for generating a
high-quality genome-scale metabolic reconstruction'', Nat Prot, 5(1):
93 - 121(2010).
- Orth, J., Thiele, I., Palsson, B. O.,"What is flux balance
analysis?", Nat Biotech, 28(3):245-8 (2010).

Regarding the Clostridium reconstruction, you will have to check if
and how your boundary conditions are set and if you are missing any
exchange, demand/sink reactions. Having set the metabolite charge to 0
will not affect the simulation.

Best regards, Ines

--
Ines Thiele, Ph.D.
Assistant Professor in Bioengineering,
Center for Systems Biology,
Faculty of Industrial Engineering, Mechanical Engineering & Computer Science
University of Iceland,
101 Reykjavik, Iceland
http://www.hi.is/~ithiele/
http://systemsbiology.hi.is/

Erlon Mendes

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Aug 17, 2011, 10:18:53 AM8/17/11

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Thank you very much Ines.
Your words helped me a lot. Now I will try the references that you
indicated me. I already read one of them (your protocol).

Best regards,

Erlon

Erlon Mendes

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Aug 17, 2011, 5:49:50 PM8/17/11

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I made some substitutions, some of them without sense, in order to
know how the reconstruction works. Now there is no gaps (i used
gapFind on it).

reactions
Rxn name Rxn description Formula Gene-reaction association Genes
Proteins Subsystem Reversible LB UB Objective

GLCt GLCt GLC[e] <=> GLC[c] 1 -1000 1000 0
HEX1HEX1 GLC[c] + ATP[c] <=> G6P[c] + ADP[c] + H[c] glk
1 -1000 1000 0
PGI PGI G6P[c] <=> F6P[c] pgi 1 -1000 1000 0
PFK PFK ATP[c] + F6P[c] -> ADP[c] + FDP[c] + H[c] (pfkA and

pfkB) 0 0 1000 0

FBA FBA FDP[c] <=> DHAP[c] + G3P[c] (fbaA and fbaB)
1 -1000 1000 0
TPI TPI DHAP[c] <=> G3P[c] tpiA 1 -1000 1000 0
GAPD GAPD G3P[c] + NAD[c] + PI[c] <=> 13DPG[c] + H[c] + NADH[c]

(gapA and gapC1 and gapC2) 1 -1000 1000 0

PI PI PI[c] <=> PI[e] 1 -1000 1000 0
NAD NAD NADH[c] <=> NAD[c] 1 -1000 1000 0
PGK PGK 13DPG[c] + ADP[c] <=> 3PG[c] + ATP[c] pgk 1 -1000
1000 0
GPM GPM 3PG[c] <=> 2PG[c] (gpmA and gpmB) 1 -1000 1000 0
ENO ENO 2PG[c] <=> H2O[c] + PEP[c] eno 1 -1000 1000 0
H2Ot H2Ot H2O[c] <=> H2O[e] 1 -1000 1000 0
PYK PYK ADP[c] + H[c] + PEP[c] -> ATP[c] + PYR[c] (pykA and
pykF) 0 0 1000 0
PYRt PYRt PYR[c] <=> PYR[e] 1 -1000 1000 1

metabolites
Metabolite name Metabolite description Metabolite neutral formula
Metabolite charged formula Metabolite charge Metabolite Compartment

13DPG[c] 3_Phospho_D_glyceroyl_phosphate C3H4O10P2 -4 cytosol
2PG[c] D_Glycerate_2_phosphate C3H4O7P -3 cytosol
3PG[c] 3_Phospho_D_glycerate C3H4O7P -3 cytosol
ADP[c] ADP C10H12N5O10P2 -3 cytosol
ATP[c] ATP C10H12N5O13P3 -4 cytosol
DHAP[c] Dihydroxyacetone_phosphate C3H5O6P -2 cytosol
F6P[c] D_Fructose_6_phosphate C6H11O9P -2 cytosol
FDP[c] D_Fructose_1_6_bisphosphate C6H10O12P2 -4 cytosol
G3P[c] Glyceraldehyde_3_phosphate C3H5O6P -2 cytosol
G6P[c] D_Glucose_6_phosphate C6H11O9P -2 cytosol
GLC[c] D_Glucose C6H12O6 0 cytosol
GLC[e] D_Glucose C6H12O6 0 extracellular
H[c] H H 1 cytosol
H2O[c] H2O H2O 0 cytosol
H2O[e] H2O H2O 0 extracellular
NAD[c] Nicotinamide_adenine_dinucleotide C21H26N7O14P2 -1 cytosol
NADH[c] Nicotinamide_adenine_dinucleotide___reduced C21H27N7O14P2 -2
cytosol
PEP[c] Phosphoenolpyruvate C3H2O6P -3 cytosol
PI[c] Phosphate HO4P -2 cytosol
PI[e] Phosphate HO4P -2 extracellular
PYR[c] Pyruvate C3H3O3 -1 cytosol
PYR[e] Pyruvate C3H3O3 -1 extracellular

Why no fluxes are observed?
Please, I need to make some fluxes appear here in order to correct a
bigger model.

Erlon

richard.que

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Aug 17, 2011, 6:50:24 PM8/17/11

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Dear Erlon,

From what I can see, your model still does not contain any exchange/
demand reactions (i.e. GLC[e] <=> , PYR[e] <=> ) and such cannot be
computed such that there is no accumulation of metabolites within the
network. With no inputs to nor outputs from the network, the only
solution which would allow for no accumulation would be zero flux.
Perhaps try looking at the E coli Core model for an example. You will
notice that some reactions (labeled with an EX for exchange reactions)
will have one metabolite as a reactant while having no products.

Hope this helps,
-Richard

K.Spear

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Aug 18, 2011, 7:52:46 PM8/18/11

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Dear all,

I am a new user of the COBRA toolbox, so my apologies if my questions
is are trivial.
However, even after an extensive reading of the multiple resources
available on the subject and a few days playing with the toolbox, I
have to admit am a bit confused with the 'boundary conditions' part.

Similarly to Erlon, I have a network that doesn't carry any flux and I
suspect we're doing the same mistakes.

- As suggested Richard, Erlon's model does not contains exchange/
demand reaction.
I am a bit confused here, as I thought the 4 foolowing reactions were
exchanges:

PYR[c] <=> PYR[e]

PI[c] <=> PI[e]

H2O[c] <=> H2O[e]

GLC[e] <=> GLC[c]

The network is small enough to be visualised properly in cellDesigner
and the representation shows a deplacement 4 metabolites from e <-> c.
Let's take the example of the pyruvate, we have something like
extrac | Cytoplasm
pyr <---|---> pyr

- Now, if we compare that with the pyruvate exchange reaction from the
ecoli_core_model. The pyruvate transport reaction is still there but
there is also an extra reaction (the actual exchange reaction if I
understood well ?).
So in this case, we have something like this : (reaction
"R_EX_pyr_LPAREN_e_RPAREN_" and reaction "R_PYRt2r" from the sbml
model)

extrac | Cytoplasm
pyr <---> pyr <---|---> pyr

- I understand input/outputs are necessary to "open" the network, but
I don't understand how, this additnal exchange
("R_EX_pyr_LPAREN_e_RPAREN_") can make the difference.

- Finally I took Erlon's example and tried to add the same type of
reactions for the 4 extracellular compounds, leaving the rest of the
network unchanged (see sbml below).
The system still doesn't carry any flux, I will try to find out what
happens. In the meantime, any suggestion/lead is more welcome.

The network beeing very small, I think it's a good training for
beginners (like me) to get familiar with the techniques.

Thanks a lot for you help

SBML file :
____________

<?xml version="1.0" encoding="UTF-8"?>
<sbml xmlns="http://www.sbml.org/sbml/level2" level="2" version="1">
<model>
<listOfUnitDefinitions>
<unitDefinition id="mmol_per_gDW_per_hr">
<listOfUnits>
<unit kind="mole" exponent="1" scale="-3" multiplier="1"
offset="0"/>
<unit kind="gram" exponent="-1" scale="0" multiplier="1"
offset="0"/>
<unit kind="second" exponent="-1" scale="0"
multiplier="0.000277777777777778" offset="0"/>
</listOfUnits>
</unitDefinition>
</listOfUnitDefinitions>
<listOfCompartments>
<compartment id="c" name="Cytoplasm" spatialDimensions="3"
constant="true"/>
<compartment id="e" name="Extracellular" spatialDimensions="3"
constant="true"/>
</listOfCompartments>
<listOfSpecies>
<species id="M_GLC_e" name="D_Glucose" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
<species id="M_GLC_c" name="D_Glucose" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
<species id="M_ATP_c" name="ATP" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -4
</body>
</notes>
</species>
<species id="M_G6P_c" name="D_Glucose_6_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_ADP_c" name="ADP" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -3
</body>
</notes>
</species>
<species id="M_H_c" name="H" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 1
</body>
</notes>
</species>
<species id="M_F6P_c" name="D_Fructose_6_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_FDP_c" name="D_Fructose_1_6_bisphosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -4
</body>
</notes>
</species>
<species id="M_DHAP_c" name="Dihydroxyacetone_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_G3P_c" name="Glyceraldehyde_3_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_NAD_c" name="Nicotinamide_adenine_dinucleotide"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -1
</body>
</notes>
</species>
<species id="M_PI_c" name="Phosphate" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_13DPG_c" name="3_Phospho_D_glyceroyl_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -4
</body>
</notes>
</species>
<species id="M_NADH_c"
name="Nicotinamide_adenine_dinucleotide___reduced" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_PI_e" name="Phosphate" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_3PG_c" name="3_Phospho_D_glycerate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -3
</body>
</notes>
</species>
<species id="M_2PG_c" name="D_Glycerate_2_phosphate"
compartment="c" hasOnlySubstanceUnits="false"
boundaryCondition="false" constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -3
</body>
</notes>
</species>
<species id="M_H2O_c" name="H2O" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
<species id="M_PEP_c" name="Phosphoenolpyruvate" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -3
</body>
</notes>
</species>
<species id="M_H2O_e" name="H2O" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
<species id="M_PYR_c" name="Pyruvate" compartment="c"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -1
</body>
</notes>
</species>
<species id="M_PYR_e" name="Pyruvate" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -1
</body>
</notes>
</species>
<species id="M_PYR_b" name="Pyruvate" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -1
</body>
</notes>
</species>
<species id="M_H2O_b" name="H2O" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
<species id="M_PI_b" name="Phosphate" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: -2
</body>
</notes>
</species>
<species id="M_GLC_b" name="D_Glucose" compartment="e"
hasOnlySubstanceUnits="false" boundaryCondition="false"
constant="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
FORMULA: 
CHARGE: 0
</body>
</notes>
</species>
</listOfSpecies>
<listOfReactions>
<reaction id="R_GLCt" name="GLCt" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_GLC_e" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_GLC_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_HEX1" name="HEX1" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: glk
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_GLC_c" stoichiometry="1"/>
<speciesReference species="M_ATP_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_G6P_c" stoichiometry="1"/>
<speciesReference species="M_ADP_c" stoichiometry="1"/>
<speciesReference species="M_H_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PGI" name="PGI" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: pgi
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_G6P_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_F6P_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PFK" name="PFK" reversible="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: (pfkA and pfkB)
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_ATP_c" stoichiometry="1"/>
<speciesReference species="M_F6P_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_ADP_c" stoichiometry="1"/>
<speciesReference species="M_H_c" stoichiometry="1"/>
<speciesReference species="M_FDP_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_FBA" name="FBA" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: (fbaA and fbaB)
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_FDP_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_DHAP_c" stoichiometry="1"/>
<speciesReference species="M_G3P_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_TPI" name="TPI" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: tpiA
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_DHAP_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_G3P_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_GAPD" name="GAPD" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: (gapA and gapC1 and gapC2)
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_G3P_c" stoichiometry="1"/>
<speciesReference species="M_NAD_c" stoichiometry="1"/>
<speciesReference species="M_PI_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_H_c" stoichiometry="1"/>
<speciesReference species="M_13DPG_c" stoichiometry="1"/>
<speciesReference species="M_NADH_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PI" name="PI" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_PI_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_PI_e" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_NAD" name="NAD" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_NADH_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_NAD_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PGK" name="PGK" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_ADP_c" stoichiometry="1"/>
<speciesReference species="M_13DPG_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_ATP_c" stoichiometry="1"/>
<speciesReference species="M_3PG_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_GPM" name="GPM" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: (gpmA and gpmB)
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_3PG_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_2PG_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_ENO" name="ENO" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: eno
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_2PG_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_H2O_c" stoichiometry="1"/>
<speciesReference species="M_PEP_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_H2Ot" name="H2Ot" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_H2O_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_H2O_e" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PYK" name="PYK" reversible="false">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: (pykA and pykF)
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_ADP_c" stoichiometry="1"/>
<speciesReference species="M_H_c" stoichiometry="1"/>
<speciesReference species="M_PEP_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_ATP_c" stoichiometry="1"/>
<speciesReference species="M_PYR_c" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_PYRt" name="PYRt" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 1
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_PYR_c" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_PYR_e" stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="1"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_R_EX" name="pyr_ex_" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_PYR_e" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_PYR_b"
stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_R_EX_H2O" name="h2o_ex_" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_H2O_e" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_H2O_b"
stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_R_EX_pho" name="pho_ex_" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_PI_e" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_PI_b"
stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
<reaction id="R_R_EX_DG" name="dg_ex_" reversible="true">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
GENE_ASSOCIATION: 
SUBSYSTEM: 
EC Number: 
Confidence Level: 
AUTHORS: 

</body>
</notes>
<listOfReactants>
<speciesReference species="M_GLC_e" stoichiometry="1"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_GLC_b"
stoichiometry="1"/>
</listOfProducts>
<kineticLaw>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<ci> FLUX_VALUE </ci>
</math>
<listOfParameters>
<parameter id="LOWER_BOUND" value="-1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="UPPER_BOUND" value="1000"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="FLUX_VALUE" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
<parameter id="OBJECTIVE_COEFFICIENT" value="0"
units="mmol_per_gDW_per_hr" constant="true"/>
</listOfParameters>
</kineticLaw>
</reaction>
</listOfReactions>
</model>
</sbml>

Mark Davids

unread,

Aug 19, 2011, 3:10:22 AM8/19/11

to cobra-...@googlegroups.com

This model does indeed not allow for production of pyruvate.
You need to add a boundary condition for protons. Glucose is
uncharged, pyruvate is charged and thus a proton is produced.
Furthermore a ATP is produced that needs to be recycled.

So add a few reactions and compounds:
M_H_c = M_H_e (exchange)
M_H_e = M_H_b (boundary condition)
M_ATP_c + M_H2O_c = M_ADP_c + M_PI_c + M_H_c (recycle)

Adding these reactions (and new compounds) should allow for pyruvate
production with the model.
You do not need the boundary condition for M_PI in this case but it
does not hurt leaving it in.

Normally you also need to recycle the NADH produced but there is a
recovery reaction in the model (NADH = NAD, mind this reaction is
unbalanced!)
To avoid this I use production of lactate as an example since the NADH
is recycled in this reaction.

Hope the model will run with addition of these reactions

Regards
Mark

Ronan Fleming

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Aug 19, 2011, 5:34:32 AM8/19/11

to cobra-...@googlegroups.com

Let Si denote a matrix of reactions that conserve mass. Let Se denote
a matrix of reactions that do not conserve mass. vi & ve are the
corresponding net internal and exchange fluxes.

[Si Se]*[vi;ve] = 0 is the (nonequilibrium) flux balance constraint
when ve is not equal to zero.

From this we have

Si*vi = -Se*ve == b

or

Si*vi = b with nonzero b (the boundary condition)

If you try to solve FBA with zero b then all vi should be zero if all
reactions in Si are mass balanced.

The COBRA toolbox function findSExRxnInd.m will attempt identify only
exchange reactions as they tend to be columns of model.S with only one
coefficient (therefore cannot be mass balanced)

Si = model.S(:,model.SIntRxnBool);
Se = model.S(:,~model.SIntRxnBool);

Try it on your models.
Ronan

function model=findSExRxnInd(model,nRealMet)
%Returns a model with boolean vectors indicating internal vs
exchange/demand/sink reactions.
%
%finds the reactions in the model which export/import from the model
%boundary
%e.g. Exchange reactions
% Demand reactions
% Sink reactions
%
%INPUT
% model
% model.biomassRxnAbbr abbreviation of biomass reaction
%
%OPTIONAL INPUT
% nRealMet specified in case extra rows in S which dont
% correspond to metabolties
%OUTPUT
% model.SIntRxnBool Boolean of internal (mass balanced) reactions.
%
% OPTIONAL OUTPUT
% model.DMRxnBool Boolean of demand reactions. Prefix 'DM_'
% model.SinkRxnBool Boolean of sink reactions. Prefix 'sink_'
%
% Ronan M.T. Fleming

--
--
Mr. Ronan MT Fleming B.V.M.S. Dip. Math. Ph.D.
-----------------------------------------------------------------
Independent Group Leader,
Center for Systems Biology,
University of Iceland,
Sturlugata 8,
101 Reykjavik,
Iceland.
http://www.hi.is/~rfleming
http://systemsbiology.hi.is/
Ph: +354 618 6245
-----------------------------------------------------------------

Erlon Mendes

unread,

Aug 19, 2011, 10:04:52 AM8/19/11

to cobra-...@googlegroups.com

I got it. The test model is working now. I hope it's useful.

Rxn name Rxn description Formula Gene-reaction association
Genes Proteins Subsystem Reversible LB UB
Objective

GLCe GLCt GLC[e] <=> 1
-1000 1000 0
GLCt GLCt GLC[e] <=> GLC[c] 1
-1000 1000 0
HEX1 HEX1 GLC[c] + ATP[c] <=> G6P[c] + ADP[c] + H[c] glk

1 -1000 1000 0
PGI PGI G6P[c] <=> F6P[c] pgi 1
-1000 1000 0
PFK PFK ATP[c] + F6P[c] -> ADP[c] + FDP[c] + H[c]
(pfkA and pfkB) 0 0 1000 0
FBA FBA FDP[c] <=> DHAP[c] + G3P[c] (fbaA and fbaB)
1 -1000 1000 0
TPI TPI DHAP[c] <=> G3P[c] tpiA 1
-1000 1000 0
GAPD GAPD G3P[c] + NAD[c] + PI[c] <=> 13DPG[c] + H[c] + NADH[c]

(gapA and gapC1 and gapC2) 1 -1000 1000 0
Ht Ht H[c] <=> H[e] 1
-1000 1000 0
He He H[e] <=> 1
-1000 1000 0
Pit Pit PI[c] <=> PI[e] 1
-1000 1000 0
Pie Pie PI[e] <=> 1

-1000 1000 0
NAD NAD NADH[c] <=> NAD[c] 1
-1000 1000 0
PGK PGK 13DPG[c] + ADP[c] <=> 3PG[c] + ATP[c] pgk
1 -1000 1000 0
GPM GPM 3PG[c] <=> 2PG[c] (gpmA and gpmB)
1 -1000 1000 0
ENO ENO 2PG[c] <=> H2O[c] + PEP[c] eno
1 -1000 1000 0

H2Ot H2Ot ATP[c] + H2O[c] <=> ADP[c] + PI[c] + H[c]
1 -1000 1000 0

PYK PYK ADP[c] + H[c] + PEP[c] -> ATP[c] + PYR[c]
(pykA and pykF) 0 0 1000 0

PYRt PYRt PYR[c] <=> PYR[e] 1
-1000 1000 1
PYRe PYRe PYR[e] <=> 1
-1000 1000 1

Metabolite name Metabolite description Metabolite neutral formula
Metabolite charged formula Metabolite charge Metabolite
Compartment
13DPG[c] 3_Phospho_D_glyceroyl_phosphate C3H4O10P2 -4
cytosol
2PG[c] D_Glycerate_2_phosphate C3H4O7P -3 cytosol
3PG[c] 3_Phospho_D_glycerate C3H4O7P -3 cytosol
ADP[c] ADP C10H12N5O10P2 -3 cytosol
ATP[c] ATP C10H12N5O13P3 -4 cytosol
DHAP[c] Dihydroxyacetone_phosphate C3H5O6P -2 cytosol
F6P[c] D_Fructose_6_phosphate C6H11O9P -2 cytosol
FDP[c] D_Fructose_1_6_bisphosphate C6H10O12P2 -4
cytosol
G3P[c] Glyceraldehyde_3_phosphate C3H5O6P -2 cytosol
G6P[c] D_Glucose_6_phosphate C6H11O9P -2 cytosol
GLC[c] D_Glucose C6H12O6 0 cytosol
GLC[e] D_Glucose C6H12O6 0 extracellular
H[c] H H 1 cytosol

H[e] H H 1 extracellular

H2O[c] H2O H2O 0 cytosol

NAD[c] Nicotinamide_adenine_dinucleotide C21H26N7O14P2 -1
cytosol
NADH[c] Nicotinamide_adenine_dinucleotide___reduced
C21H27N7O14P2 -2 cytosol
PEP[c] Phosphoenolpyruvate C3H2O6P -3 cytosol
PI[c] Phosphate HO4P -2 cytosol
PI[e] Phosphate HO4P -2 extracellular
PYR[c] Pyruvate C3H3O3 -1 cytosol
PYR[e] Pyruvate C3H3O3 -1 extracellular

Thank you very much. This gave me a new hope.

Best regards,

Erlon

-----Mensagem original-----
De: cobra-...@googlegroups.com [mailto:cobra-...@googlegroups.com]
Em nome de Ronan Fleming
Enviada em: sexta-feira, 19 de agosto de 2011 06:35
Para: cobra-...@googlegroups.com
Assunto: Re: doubts about reconstructions

SV

unread,

Oct 4, 2016, 3:35:04 PM10/4/16

to COBRA Toolbox

Hi Erlon:

I tried what you suggested in your earlier response- fixing lb-ub for exchange reactions in the model which was converted from xls to cobra model using xls2model function.. Still I'm getting zero biomass. Appreciate any help. Thanks!!

FBAsolutionTest1 =

           x: [1935x1 double]
           f: 0
           y: [1574x1 double]
           w: [1935x1 double]
        stat: 1
    origStat: 'OPTIMAL'
      solver: 'gurobi6'
        time: 0.0155

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Erlon Mendes

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Oct 7, 2016, 4:28:11 PM10/7/16

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Hi Seema,

For a genomic scale model has some growth is necessary for all the way to the objective function is not restricted, i.e. that all metabolites needed for the biomass are available at metabolic pathways. If a metabolite is not limiting, create an exchange reaction of -1000 to 1000 allowing its use, but absolutely no metabolite required in all reactions from its substrate to biomass may be missing. This is usually a difficult task with a large stoichiometric matrix like yours, but nothing that mathematical logic can not solve. Your model is resulting in zero simply because this is the only solution allowed within the space you delimited.

Best wishes,

Erlon Mendes, D. Sc.

13DPG[c]        3_Phospho_D_ glyceroyl_phosphate                 C3H4O10P2        -4
cytosol
2PG[c]        D_Glycerate_2_ phosphate                 C3H4O7P        -3         cytosol
3PG[c]        3_Phospho_D_ glycerate                 C3H4O7P        -3         cytosol

ADP[c]        ADP                 C10H12N5O10P2        -3         cytosol
ATP[c]        ATP                 C10H12N5O13P3        -4         cytosol
DHAP[c]         Dihydroxyacetone_phosphate                 C3H5O6P        -2        cytosol

F6P[c]        D_Fructose_6_ phosphate                 C6H11O9P        -2         cytosol
FDP[c]        D_Fructose_1_6_ bisphosphate                 C6H10O12P2        -4
cytosol
G3P[c]        Glyceraldehyde_ 3_phosphate                 C3H5O6P        -2         cytosol
G6P[c]        D_Glucose_6_ phosphate                 C6H11O9P        -2         cytosol

GLC[c]        D_Glucose                 C6H12O6        0         cytosol
GLC[e]        D_Glucose                 C6H12O6        0         extracellular
H[c]        H                 H        1        cytosol
H[e]        H                 H        1         extracellular
H2O[c]        H2O                 H2O        0        cytosol

NAD[c] Nicotinamide_ adenine_dinucleotide C21H26N7O14P2 -1

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