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BIOMD0000000212 - Curien2009_Aspartate_Metabolism

 

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Reference Publication
Publication ID: 19455135
Curien G, Bastien O, Robert-Genthon M, Cornish-Bowden A, Cárdenas ML, Dumas R.
Understanding the regulation of aspartate metabolism using a model based on measured kinetic parameters.
Mol. Syst. Biol. 2009; 5: 271
CNRS, UMR 5168, 17 rue des Martyrs, Grenoble, France. gcurien@cea.fr  [more]
Model
Original Model: BIOMD0000000212.origin
Submitter: Gilles Curien
Submission ID: MODEL3336584391
Submission Date: 28 May 2009 15:24:01 UTC
Last Modification Date: 13 Dec 2010 09:51:40 UTC
Creation Date: 28 May 2009 12:57:42 UTC
Encoders:  Lukas Endler
   Gilles Curien
set #1
bqbiol:isPartOf KEGG Pathway Glycine, serine and threonine metabolism - Arabidopsis thaliana (thale cress)
bqbiol:isVersionOf Gene Ontology aspartate metabolic process
bqbiol:occursIn Taxonomy Arabidopsis thaliana
Notes

This a model described in the article:
Understanding the regulation of aspartate metabolism using a model based on measured kinetic parameters.
Curien G, Bastien O, Robert-Genthon M, Cornish-Bowden A, Cárdenas ML, Dumas R. Mol Syst Biol. 2009;5:271. Epub 2009 May 19. PMID: 19455135 , doi: 10.1038/msb.2009.29
Abstract:
The aspartate-derived amino-acid pathway from plants is well suited for analysing the function of the allosteric network of interactions in branched pathways. For this purpose, a detailed kinetic model of the system in the plant model Arabidopsis was constructed on the basis of in vitro kinetic measurements. The data, assembled into a mathematical model, reproduce in vivo measurements and also provide non-intuitive predictions. A crucial result is the identification of allosteric interactions whose function is not to couple demand and supply but to maintain a high independence between fluxes in competing pathways. In addition, the model shows that enzyme isoforms are not functionally redundant, because they contribute unequally to the flux and its regulation. Another result is the identification of the threonine concentration as the most sensitive variable in the system, suggesting a regulatory role for threonine at a higher level of integration.

The limiting rates for the tRNA synthetase reactions, V_Lys_RS, V_Thr_RS and V_Ile_RS, are all assigned a joined value, Vmax_AA_RS, to facilitate reproduction of the results in the publication. To alter these rates seperately these assignments have to be changed or removed.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use .
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 19455135 Submission Date: 28 May 2009 15:24:01 UTC Last Modification Date: 13 Dec 2010 09:51:40 UTC Creation Date: 28 May 2009 12:57:42 UTC
Mathematical expressions
Reactions
Aspartate kinase 1 react. Aspartate kinase 2 react. aspartate kinase react. (AKI-HSDHI) aspartate kinase react. (AKII-HSDHII)
Aspartate semialdehyde dehydrogenase react. DHDPS1 react. DHDPS2 react. homoserine dehydrogenase react. (AKI-HSDHI)
homoserine dehydrogenase react. (AKII-HSDHII) homoserine kinase react. Threonine synthase react. (TS1) Cystathionine gamma synthase react.
Threonine deaminase react. Lys aminoacyl tRNA synthetase react. Thr aminoacyl tRNA synthetase react. Ile aminoacyl tRNA synthetase react.
Lys ketoglutarate reductase react. Thr aldolase react.    
Rules
Assignment Rule (variable: V_Lys_RS) Assignment Rule (variable: V_Thr_RS) Assignment Rule (variable: V_Ile_RS)  
Physical entities
Compartments Species
chl Aspartate AK1 Lysine
S-adenosyl-methionine Aspartyl_P AK2
AKI-HSDHI AKII-HSDHII Threonine
ASADH Aspartate semialdehyde DHDPS1
DHDPS2 Homoserine Phosphohomoserine
HSK TS1 Phosphate
Cysteine CGS Cystathione
TD Isoleucine Valine
Lys-tRNA Thr-tRNA Ile-tRNA
LKR Saccharopine THA
Glycine    
Global parameters
V_Lys_RS V_Thr_RS V_Ile_RS Vmax_AA_RS
Reactions (18)
 
 Aspartate kinase 1 react. [Aspartate] ↔ [Aspartyl_P];   {AK1} , {Lysine} , {S-adenosyl-methionine}
 
 Aspartate kinase 2 react. [Aspartate] ↔ [Aspartyl_P];   {AK2} , {Lysine}
 
 aspartate kinase react. (AKI-HSDHI) [Aspartate] ↔ [Aspartyl_P];   {AKI-HSDHI} , {Threonine}
 
 aspartate kinase react. (AKII-HSDHII) [Aspartate] ↔ [Aspartyl_P];   {AKII-HSDHII} , {Threonine}
 
 Aspartate semialdehyde dehydrogenase react. [Aspartyl_P] ↔ [Aspartate semialdehyde];   {ASADH}
 
 DHDPS1 react. [Aspartate semialdehyde] → [Lysine];   {DHDPS1} , {Lysine}
 
 DHDPS2 react. [Aspartate semialdehyde] → [Lysine];   {DHDPS2} , {Lysine}
 
 homoserine dehydrogenase react. (AKI-HSDHI) [Aspartate semialdehyde] ↔ [Homoserine];   {AKI-HSDHI} , {Threonine}
 
 homoserine dehydrogenase react. (AKII-HSDHII) [Aspartate semialdehyde] ↔ [Homoserine];   {AKII-HSDHII} , {Threonine}
 
 homoserine kinase react. [Homoserine] → [Phosphohomoserine];   {HSK}
 
 Threonine synthase react. (TS1) [Phosphohomoserine] → [Threonine];   {TS1} , {Phosphate} , {S-adenosyl-methionine}
 
 Cystathionine gamma synthase react. [Phosphohomoserine] → [Cystathione];   {CGS} , {Cysteine} , {Phosphate}
 
 Threonine deaminase react. [Threonine] → [Isoleucine];   {TD} , {Valine} , {Isoleucine}
 
 Lys aminoacyl tRNA synthetase react. [Lysine] → [Lys-tRNA];  
 
 Thr aminoacyl tRNA synthetase react. [Threonine] → [Thr-tRNA];  
 
 Ile aminoacyl tRNA synthetase react. [Isoleucine] → [Ile-tRNA];  
 
 Lys ketoglutarate reductase react. [Lysine] → [Saccharopine];   {LKR}
 
 Thr aldolase react. [Threonine] → [Glycine];   {THA}
 
Rules (3)
 
 Assignment Rule (name: V_Lys_RS) V_Lys_RS = V_AA_RS
 
 Assignment Rule (name: V_Thr_RS) V_Thr_RS = V_AA_RS
 
 Assignment Rule (name: V_Ile_RS) V_Ile_RS = V_AA_RS
 
 chl Spatial dimensions: 3.0  Compartment size: 1.0
 
 Aspartate
Compartment: chl
Initial concentration: 1500.0
 
 AK1
Compartment: chl
Initial concentration: 0.25
 
 Lysine
Compartment: chl
Initial concentration: 0.0
 
 S-adenosyl-methionine
Compartment: chl
Initial concentration: 20.0
 
 Aspartyl_P
Compartment: chl
Initial concentration: 0.0
 
 AK2
Compartment: chl
Initial concentration: 0.25
 
 AKI-HSDHI
Compartment: chl
Initial concentration: 0.63
 
 AKII-HSDHII
Compartment: chl
Initial concentration: 0.63
 
 Threonine
Compartment: chl
Initial concentration: 0.0
 
 ASADH
Compartment: chl
Initial concentration: 11.6
 
 Aspartate semialdehyde
Compartment: chl
Initial concentration: 0.0
 
 DHDPS1
Compartment: chl
Initial concentration: 1.6
 
 DHDPS2
Compartment: chl
Initial concentration: 1.6
 
 Homoserine
Compartment: chl
Initial concentration: 0.0
 
 Phosphohomoserine
Compartment: chl
Initial concentration: 0.0
 
 HSK
Compartment: chl
Initial concentration: 4.0
 
 TS1
Compartment: chl
Initial concentration: 7.4
 
 Phosphate
Compartment: chl
Initial concentration: 10000.0
 
 Cysteine
Compartment: chl
Initial concentration: 15.0
 
 CGS
Compartment: chl
Initial concentration: 0.7
 
 Cystathione
Compartment: chl
Initial concentration: 0.0
 
 TD
Compartment: chl
Initial concentration: 0.36
 
 Isoleucine
Compartment: chl
Initial concentration: 0.0
 
 Valine
Compartment: chl
Initial concentration: 100.0
 
 Lys-tRNA
Compartment: chl
Initial concentration: 0.0
 
 Thr-tRNA
Compartment: chl
Initial concentration: 0.0
 
 Ile-tRNA
Compartment: chl
Initial concentration: 0.0
 
 LKR
Compartment: chl
Initial concentration: 0.0
 
 Saccharopine
Compartment: chl
Initial concentration: 0.0
 
 THA
Compartment: chl
Initial concentration: 0.0
 
 Glycine
Compartment: chl
Initial concentration: 0.0
 
Global Parameters (4)
 
   V_Lys_RS
Value: 0.43   (Units: umole_per_litre_per_time)
 
   V_Thr_RS
Value: 0.43   (Units: umole_per_litre_per_time)
 
   V_Ile_RS
Value: 0.43   (Units: umole_per_litre_per_time)
 
   Vmax_AA_RS
Value: 0.43   (Units: umole_per_litre_per_time)
Constant
 
Aspartate kinase 1 react. (5)
 
 AK1_kforward_app_exp
Value: 5.65   (Units: per_time)
Constant
 
 AK1_kreverse_app_exp
Value: 1.6   (Units: litre_per_umole_per_time)
Constant
 
 AK1_Lys_Ki_app_exp
Value: 550.0   (Units: umole_per_litre)
Constant
 
 AK1_AdoMet_Ka_app_exp
Value: 3.5   (Units: umole_per_litre)
Constant
 
 AK1_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
Aspartate kinase 2 react. (4)
 
 AK2_kforward_app_exp
Value: 3.15   (Units: per_time)
Constant
 
 AK2_kreverse_app_exp
Value: 0.86   (Units: litre_per_umole_per_time)
Constant
 
 AK2_Lys_Ki_app_exp
Value: 22.0   (Units: umole_per_litre)
Constant
 
 AK2_nH_exp
Value: 1.1   (Units: dimensionless)
Constant
 
aspartate kinase react. (AKI-HSDHI) (4)
 
 AKI_kforward_app_exp
Value: 0.36   (Units: per_time)
Constant
 
 AKI_kreverse_app_exp
Value: 0.15   (Units: litre_per_umole_per_time)
Constant
 
 AKI_Thr_Ki_app_exp
Value: 124.0   (Units: umole_per_litre)
Constant
 
 AKI_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
aspartate kinase react. (AKII-HSDHII) (4)
 
 AKII_kforward_app_exp
Value: 1.35   (Units: per_time)
Constant
 
 AKII_kreverse_app_exp
Value: 0.22   (Units: litre_per_umole_per_time)
Constant
 
 AKII_Thr_Ki_app_exp
Value: 109.0   (Units: umole_per_litre)
Constant
 
 AKII_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
Aspartate semialdehyde dehydrogenase react. (2)
 
 ASADH_kforward_app_exp
Value: 0.9   (Units: litre_per_umole_per_time)
Constant
 
 ASADH_kreverse_app_exp
Value: 0.23   (Units: litre_per_umole_per_time)
Constant
 
DHDPS1 react. (3)
 
 DHDPS1_k_app_exp
Value: 1.0   (Units: umole_per_litre)
Constant
 
 DHDPS1_Lys_Ki_app_exp
Value: 10.0   (Units: umole_per_litre)
Constant
 
 DHDPS1_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
DHDPS2 react. (3)
 
 DHDPS2_k_app_exp
Value: 1.0   (Units: umole_per_litre)
Constant
 
 DHDPS2_Lys_Ki_app_exp
Value: 33.0   (Units: umole_per_litre)
Constant
 
 DHDPS2_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
homoserine dehydrogenase react. (AKI-HSDHI) (4)
 
   HSDHI_kforward_app_exp
Value: 0.84   (Units: litre_per_umole_per_time)
Constant
 
   HSDHI_Thr_relative_residual_activity_app_exp
Value: 0.14   (Units: dimensionless)
Constant
 
   HSDHI_Thr_relative_inhibition_app_exp
Value: 0.86   (Units: dimensionless)
Constant
 
   HSDHI_Thr_Ki_app_exp
Value: 400.0   (Units: umole_per_litre)
Constant
 
homoserine dehydrogenase react. (AKII-HSDHII) (4)
 
   HSDHII_kforward_app_exp
Value: 0.64   (Units: litre_per_umole_per_time)
Constant
 
   HSDHII_Thr_relative_residual_activity_app_exp
Value: 0.25   (Units: dimensionless)
Constant
 
   HSDHII_Thr_relative_inhibition_app_exp
Value: 0.75   (Units: dimensionless)
Constant
 
   HSDHII_Thr_Ki_app_exp
Value: 8500.0   (Units: umole_per_litre)
Constant
 
homoserine kinase react. (2)
 
   HSK_kcat_app_exp
Value: 2.8   (Units: per_time)
Constant
 
   HSK_Hser_app_exp
Value: 14.0   (Units: umole_per_litre)
Constant
 
Threonine synthase react. (TS1) (9)
 
   TS1_kcatmin_exp
Value: 0.42   (Units: dimensionless)
Constant
 
   TS1_AdoMet_kcatmax_exp
Value: 3.5   (Units: dimensionless)
Constant
 
   TS1_AdoMet_Ka1_exp
Value: 73.0   (Units: umole2_per_litre2)
Constant
 
   TS1_nH_exp
Value: 2.0   (Units: dimensionless)
Constant
 
   TS1_Phosphate_Ki_exp
Value: 1000.0   (Units: umole_per_litre)
Constant
 
   TS1_AdoMEt_Km_no_AdoMet_exp
Value: 250.0   (Units: dimensionless)
Constant
 
   TS1_AdoMet_Ka2_exp
Value: 0.5   (Units: dimensionless)
Constant
 
   TS1_AdoMet_Ka3_exp
Value: 1.09   (Units: dimensionless)
Constant
 
   TS1_AdoMet_Ka4_exp
Value: 140.0   (Units: umole2_per_litre2)
Constant
 
Cystathionine gamma synthase react. (4)
 
   CGS_kcat_exp
Value: 30.0   (Units: dimensionless)
Constant
 
   CGS_Cys_Km_exp
Value: 460.0   (Units: dimensionless)
Constant
 
   CGS_Phser_Km_exp
Value: 2500.0   (Units: dimensionless)
Constant
 
   CGS_Phosphate_Ki_exp
Value: 2000.0   (Units: dimensionless)
Constant
 
Threonine deaminase react. (5)
 
   TD_k_app_exp
Value: 0.0124   (Units: dimensionless)
Constant
 
   TD_Ile_Ki_no_Val_app_exp
Value: 30.0   (Units: dimensionless)
Constant
 
   TD_Val_Ka1_app_exp
Value: 73.0   (Units: dimensionless)
Constant
 
   TD_Val_Ka2_app_exp
Value: 615.0   (Units: umole_per_litre)
Constant
 
   TD_nH_app_exp
Value: 3.0   (Units: dimensionless)
Constant
 
Lys aminoacyl tRNA synthetase react. (1)
 
   Lys_tRNAS_Lys_Km
Value: 25.0   (Units: umole_per_litre)
Constant
 
Thr aminoacyl tRNA synthetase react. (1)
 
   Thr_tRNAS_Thr_Km
Value: 100.0   (Units: umole_per_litre)
Constant
 
Ile aminoacyl tRNA synthetase react. (1)
 
   Ile_tRNAS_Ile_Km
Value: 20.0   (Units: umole_per_litre)
Constant
 
Lys ketoglutarate reductase react. (2)
 
   LKR_kcat_exp
Value: 3.1   (Units: per_time)
Constant
 
   LKR_Lys_Km_exp
Value: 13000.0   (Units: umole_per_litre)
Constant
 
Thr aldolase react. (2)
 
   THA_kcat_exp
Value: 1.7   (Units: per_time)
Constant
 
   THA_Thr_Km_exp
Value: 7100.0   (Units: umole_per_litre)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000212

Curator's comment: (updated: 13 Dec 2010 01:41:13 GMT)

Reproduction of figure 7c of the original publication using Copasi 4.6. Steady states were calculated over a range of values for the maximal velocity of tRNA synthetase, V_max_AA_RS using the parameter scan task of Copasi (250 intervals from 0.15 to 2 uM/s). As steady state fluxes in the protein branches, the fluxes through the Lys, Thr, and Ile tRNA synthetase reactions were taken.

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