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BIOMD0000000211 - Albert2005_Glycolysis

 

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Reference Publication
Publication ID: 15955817
Albert MA, Haanstra JR, Hannaert V, Van Roy J, Opperdoes FR, Bakker BM, Michels PA.
Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei.
J. Biol. Chem. 2005 Aug; 280(31): 28306-28315
Research Unit for Tropical Diseases, Christian de Duve Institute of Cellular Pathology and Laboratory of Biochemistry, UniversitĂ© Catholique de Louvain, B-1200 Brussels, Belgium.  [more]
Model
Original Model: BIOMD0000000211.origin
Submitter: Marvin Schulz
Submission ID: MODEL1511155915
Submission Date: 28 Jan 2009 11:34:41 UTC
Last Modification Date: 08 Apr 2016 16:01:32 UTC
Creation Date: 27 Jan 2009 14:07:41 UTC
Encoders:  Vijayalakshmi Chelliah
   Marvin Schulz
   Paul A. M. Michels
set #1
bqbiol:is KEGG Pathway Glycolysis / Gluconeogenesis - Trypanosoma brucei
bqbiol:isVersionOf Gene Ontology glycolytic process
bqbiol:isHomologTo Reactome REACT_1383
set #2
bqbiol:hasTaxon Taxonomy Trypanosoma brucei
set #3
bqmodel:isDerivedFrom BioModels Database Bakker1997_Glycolysis
BioModels Database Bakker2001_Glycolysis
PubMed 10329645
Notes

This model is from the article:
Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei.
Albert MA, Haanstra JR, Hannaert V, Van Roy J, Opperdoes FR, Bakker BM, Michels PA. J Biol Chem2005 Aug 5;280(31):28306-15. 15955817,
Abstract:
A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was developed previously on the basis of all available enzyme kinetic data (Bakker, B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol. Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular metabolite concentrations as measured in non-growing trypanosomes and the major contribution to the flux control exerted by the plasma membrane glucose transporter. Surprisingly, a large overcapacity was predicted for hexokinase (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our further analysis of the control of glycolytic flux in bloodstream form T. brucei. First, the model was optimized and extended with recent information about the kinetics of enzymes and their activities as measured in lysates of in vitro cultured growing trypanosomes. Second, the concentrations of five glycolytic enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes were changed by RNA interference. The effects of the knockdown of these enzymes on the growth, activities, and levels of various enzymes and glycolytic flux were studied and compared with model predictions. Data thus obtained support the conclusion from the in silico analysis that HXK, PFK, and PYK are in excess, albeit less than predicted. Interestingly, depletion of PFK and enolase had an effect on the activity (but not, or to a lesser extent, expression) of some other glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like organelles harboring the first seven enzymes of the glycolytic pathway of trypanosomes) and in the cytosol were affected. These data suggest the existence of novel regulatory mechanisms operating in trypanosome glycolysis.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2012 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 15955817 Submission Date: 28 Jan 2009 11:34:41 UTC Last Modification Date: 08 Apr 2016 16:01:32 UTC Creation Date: 27 Jan 2009 14:07:41 UTC
Mathematical expressions
Reactions
glucose transport hexokinase phosphoglycerate isomerase phophofructokinase
aldolase triosephosphate isomerase glyceraldehyde3phosphatedehydrogenase glycerol3phosphatedehydrogenase
glycerol3phosphate oxidase pyruvate transport phosphoglycerate kinase pyruvate kinase
atp utilisation glycerol kinase phosphoglycerate mutase enolase
adenylate kinase cytosol adenylate kinase glycosome 3phosphoglycerate transport gly3p dhap antiporter
glycerol transport      
Physical entities
Compartments Species
cytosol pyruvate adpc atpc
phosphoenolpyruvate 2phosphoglycerate ampc
3phosphoglycerate cytosol dihydroxyacetonephosphate cytosol glycerol3phosphate cytosol
     
glycosome glucose atpg adpg
ampg glucose6phosphate fructose6phosphate
fructose16bisphosphate dihydroxyacetonephosphate glyceraldehyde3phosphate
nad nadh bisphosphoglycerate
glycerol3phosphate 3phosphoglycerate glycerol
     
extracellular glucose external pyruvate external glycerol external
Global parameters
RaHXK RaPFK RaPYK RaPGAM
RaENO      
Reactions (21)
 
 glucose transport [glucose external] ↔ [glucose];  
 
 hexokinase [glucose] + [atpg] ↔ [glucose6phosphate] + [adpg];  
 
 phosphoglycerate isomerase [glucose6phosphate] ↔ [fructose6phosphate];  
 
 phophofructokinase [fructose6phosphate] + [atpg] ↔ [fructose16bisphosphate] + [adpg];  
 
 aldolase [fructose16bisphosphate] ↔ [dihydroxyacetonephosphate] + [glyceraldehyde3phosphate];   {atpg} , {adpg} , {ampg}
 
 triosephosphate isomerase [dihydroxyacetonephosphate] ↔ [glyceraldehyde3phosphate];  
 
 glyceraldehyde3phosphatedehydrogenase [glyceraldehyde3phosphate] + [nad] ↔ [bisphosphoglycerate] + [nadh];  
 
 glycerol3phosphatedehydrogenase [dihydroxyacetonephosphate] + [nadh] ↔ [nad] + [glycerol3phosphate];  
 
 glycerol3phosphate oxidase [glycerol3phosphate cytosol] → [dihydroxyacetonephosphate cytosol];  
 
 pyruvate transport [pyruvate] → [pyruvate external];  
 
 phosphoglycerate kinase [bisphosphoglycerate] + [adpg] ↔ [3phosphoglycerate] + [atpg];  
 
 pyruvate kinase [phosphoenolpyruvate] + [adpc] ↔ [pyruvate] + [atpc];  
 
 atp utilisation [atpc] → [adpc];  
 
 glycerol kinase [glycerol3phosphate] + [adpg] ↔ [glycerol] + [atpg];  
 
 phosphoglycerate mutase [3phosphoglycerate cytosol] ↔ [2phosphoglycerate];  
 
 enolase [2phosphoglycerate] ↔ [phosphoenolpyruvate];  
 
 adenylate kinase cytosol [atpc] + [ampc] ↔ 2.0 × [adpc];  
 
 adenylate kinase glycosome [atpg] + [ampg] ↔ 2.0 × [adpg];  
 
 3phosphoglycerate transport [3phosphoglycerate] ↔ [3phosphoglycerate cytosol];  
 
 gly3p dhap antiporter [glycerol3phosphate] + [dihydroxyacetonephosphate cytosol] ↔ [glycerol3phosphate cytosol] + [dihydroxyacetonephosphate];  
 
 glycerol transport [glycerol] ↔ [glycerol external];  
 
Functions (13)
 
 Henri-Michaelis-Menten (irreversible) lambda(substrate, Km, V, V*substrate/(Km+substrate))
 
 Reversible Michaelis-Menten lambda(substrate, product, Kms, Kmp, Vf, Vr, (Vf*substrate/Kms-Vr*product/Kmp)/(1+substrate/Kms+product/Kmp))
 
 Rate Law for glyceraldehyde3phosphatedehydrogenase lambda(Vmax_v7, GAP, KGAP_v7, NAD, KNAD_v7, r_v7, BPGA13, KBPGA13_v7, NADH, KNADH_v7, Vmax_v7*(GAP/KGAP_v7*NAD/KNAD_v7-r_v7*BPGA13/KBPGA13_v7*NADH/KNADH_v7)/((1+GAP/KGAP_v7+BPGA13/KBPGA13_v7)*(1+NAD/KNAD_v7+NADH/KNADH_v7)))
 
 Rate Law for atp utilisation lambda(k, atpc, adpc, k*atpc/adpc)
 
 Rate Law for pyruvate kinase lambda(Vmax_v12, PEP, PK_n, ADPc, KADP_v12, ATPc, Vmax_v12*(PEP/(0.34*(1+ATPc/0.57+ADPc/0.64)))^PK_n*ADPc/KADP_v12/((1+(PEP/(0.34*(1+ATPc/0.57+ADPc/0.64)))^PK_n)*(1+ADPc/KADP_v12)))
 
 Rate Law for glycerol3phosphatedehydrogenase lambda(Vmax_v8, DHAPg, KDHAPg_v8, NADH, KNADH_v8, r_v8, NAD, KNAD_v8, Gly3Pg, KGly3Pg_v8, Vmax_v8*(DHAPg/KDHAPg_v8*NADH/KNADH_v8-r_v8*NAD/KNAD_v8*Gly3Pg/KGly3Pg_v8)/((1+DHAPg/KDHAPg_v8+Gly3Pg/KGly3Pg_v8)*(1+NADH/KNADH_v8+NAD/KNAD_v8)))
 
 Rate Law for phosphoglycerate kinase lambda(Vmax_v11, BPGA13, KBPGA13_v11, ADPg, KADPg_v11, r_v11, PGA3, KPGA3_v11, ATPg, KATPg_v11, Vmax_v11*(BPGA13/KBPGA13_v11*ADPg/KADPg_v11-r_v11*PGA3/KPGA3_v11*ATPg/KATPg_v11)/((1+BPGA13/KBPGA13_v11+PGA3/KPGA3_v11)*(1+ADPg/KADPg_v11+ATPg/KATPg_v11)))
 
 Rate Law for phophofructokinase lambda(Vmax_v4, Ki1Fru16BP_v4, Fru16BP, Fru6P, KFru6P_v4, ATPg, KATPg_v4, Ki2Fru16BP_v4, Vmax_v4*Ki1Fru16BP_v4/(Ki1Fru16BP_v4+Fru16BP)*Fru6P/KFru6P_v4*ATPg/KATPg_v4/((1+Fru6P/KFru6P_v4+Fru16BP/Ki2Fru16BP_v4)*(1+ATPg/KATPg_v4)))
 
 Rate Law for glycerol kinase lambda(Vmax_v14, Gly3Pg, KGly3Pg_v14, ADPg, KADPg_v14, r_v14, Glycerol, KGlycerol_v14, ATPg, KATPg_v14, Vmax_v14*(Gly3Pg/KGly3Pg_v14*ADPg/KADPg_v14-r_v14*Glycerol/KGlycerol_v14*ATPg/KATPg_v14)/((1+Gly3Pg/KGly3Pg_v14+Glycerol/KGlycerol_v14)*(1+ADPg/KADPg_v14+ATPg/KATPg_v14)))
 
 Rate Law for hexokinase lambda(Vmax_v2, GlucoseInt, KGlcInt_v2, ATPg, KATPg_v2, ADPg, KADPg_v2, Glc6P, KGlc6P_v2, Vmax_v2*GlucoseInt/KGlcInt_v2*ATPg/KATPg_v2/((1+ATPg/KATPg_v2+ADPg/KADPg_v2)*(1+GlucoseInt/KGlcInt_v2+Glc6P/KGlc6P_v2)))
 
 Rate Law for aldolase lambda(Vmax_v5, Fru16BP, GAP, DHAPg, Keq_v5, ATPg, ADPg, AMPg, r_v5, KGAP_v5, KGAPi_v5, Vmax_v5*(Fru16BP-GAP*DHAPg/Keq_v5)/(0.009*(1+ATPg/0.68+ADPg/1.51+AMPg/3.65)+Fru16BP+GAP*0.015*(1+ATPg/0.68+ADPg/1.51+AMPg/3.65)/Keq_v5*1/r_v5+DHAPg*KGAP_v5/Keq_v5*1/r_v5+Fru16BP*GAP/KGAPi_v5+GAP*DHAPg/Keq_v5*1/r_v5))
 
 Rate Law for adenylate kinase lambda(k, atp, amp, keqak, adp, k*(atp*amp-keqak*adp*adp))
 
 Rate Law for glucose transport lambda(Vmax_v1, GlucoseExt, GlucoseInt, KGlc, Alpha_v1, Vmax_v1*(GlucoseExt-GlucoseInt)/(KGlc+GlucoseExt+GlucoseInt+Alpha_v1*GlucoseExt*GlucoseInt/KGlc))
 
 cytosol Spatial dimensions: 3.0  Compartment size: 1.0
 
 pyruvate
Compartment: cytosol
Initial concentration: 10.0
 
 adpc
Compartment: cytosol
Initial concentration: 1.31652277625
 
 atpc
Compartment: cytosol
Initial concentration: 0.341738611875
 
 phosphoenolpyruvate
Compartment: cytosol
Initial concentration: 0.0
 
 2phosphoglycerate
Compartment: cytosol
Initial concentration: 0.0
 
 ampc
Compartment: cytosol
Initial concentration: 2.24173861188
 
 3phosphoglycerate cytosol
Compartment: cytosol
Initial concentration: 0.0
 
 dihydroxyacetonephosphate cytosol
Compartment: cytosol
Initial concentration: 2.23134594788
 
 glycerol3phosphate cytosol
Compartment: cytosol
Initial concentration: 2.76865405212
 
 glycosome Spatial dimensions: 3.0  Compartment size: 1.0
 
 glucose
Compartment: glycosome
Initial concentration: 0.0
 
 atpg
Compartment: glycosome
Initial concentration: 0.240501857508
 
 adpg
Compartment: glycosome
Initial concentration: 1.51899628498
 
 ampg
Compartment: glycosome
Initial concentration: 4.24050185751
 
 glucose6phosphate
Compartment: glycosome
Initial concentration: 0.5
 
 fructose6phosphate
Compartment: glycosome
Initial concentration: 0.5
 
 fructose16bisphosphate
Compartment: glycosome
Initial concentration: 10.0
 
 dihydroxyacetonephosphate
Compartment: glycosome
Initial concentration: 8.47911460193
 
 glyceraldehyde3phosphate
Compartment: glycosome
Initial concentration: 2.5
 
 nad
Compartment: glycosome
Initial concentration: 2.0
 
 nadh
Compartment: glycosome
Initial concentration: 2.0
 
 bisphosphoglycerate
Compartment: glycosome
Initial concentration: 0.5
 
 glycerol3phosphate
Compartment: glycosome
Initial concentration: 10.5208853981
 
 3phosphoglycerate
Compartment: glycosome
Initial concentration: 0.0
 
 glycerol
Compartment: glycosome
Initial concentration: 0.0
 
 extracellular Spatial dimensions: 3.0  Compartment size: 1.0
 
 glucose external
Compartment: extracellular
Initial concentration: 5.0
Constant
 
 pyruvate external
Compartment: extracellular
Initial concentration: 0.0
Constant
 
 glycerol external
Compartment: extracellular
Initial concentration: 0.0
Constant
 
Global Parameters (5)
 
   RaHXK
Value: 1.0
Constant
 
   RaPFK
Value: 1.0
Constant
 
   RaPYK
Value: 1.0
Constant
 
   RaPGAM
Value: 1.0
Constant
 
   RaENO
Value: 1.0
Constant
 
glucose transport (3)
 
   Vmax_v1
Value: 108.9
Constant
 
   KGlc
Value: 1.0
Constant
 
   Alpha_v1
Value: 0.75
Constant
 
hexokinase (5)
 
   Vmax_v2
Value: 1929.0
Constant
 
   KGlcInt_v2
Value: 0.1
Constant
 
   KATPg_v2
Value: 0.116
Constant
 
   KADPg_v2
Value: 0.126
Constant
 
   KGlc6P_v2
Value: 12.0
Constant
 
phosphoglycerate isomerase (4)
 
   Kms
Value: 0.4
Constant
 
   Kmp
Value: 0.12
Constant
 
   Vf
Value: 1305.0
Constant
 
   Vr
Value: 1305.0
Constant
 
phophofructokinase (5)
 
   Vmax_v4
Value: 1708.0
Constant
 
   Ki1Fru16BP_v4
Value: 15.8
Constant
 
   KFru6P_v4
Value: 0.82
Constant
 
   KATPg_v4
Value: 0.026
Constant
 
   Ki2Fru16BP_v4
Value: 10.7
Constant
 
aldolase (5)
 
   Vmax_v5
Value: 560.0
Constant
 
   Keq_v5
Value: 0.069
Constant
 
   r_v5
Value: 1.19
Constant
 
   KGAP_v5
Value: 0.067
Constant
 
   KGAPi_v5
Value: 0.098
Constant
 
triosephosphate isomerase (4)
 
   Kms
Value: 1.2
Constant
 
   Kmp
Value: 0.25
Constant
 
   Vf
Value: 999.3
Constant
 
   Vr
Value: 5696.01
Constant
 
glyceraldehyde3phosphatedehydrogenase (6)
 
   Vmax_v7
Value: 720.9
Constant
 
   KGAP_v7
Value: 0.15
Constant
 
   KNAD_v7
Value: 0.45
Constant
 
   r_v7
Value: 0.67
Constant
 
   KBPGA13_v7
Value: 0.1
Constant
 
   KNADH_v7
Value: 0.02
Constant
 
glycerol3phosphatedehydrogenase (6)
 
   Vmax_v8
Value: 465.0
Constant
 
   KDHAPg_v8
Value: 0.1
Constant
 
   KNADH_v8
Value: 0.01
Constant
 
   r_v8
Value: 0.28
Constant
 
   KNAD_v8
Value: 0.4
Constant
 
   KGly3Pg_v8
Value: 2.0
Constant
 
glycerol3phosphate oxidase (2)
 
   Km
Value: 1.7
Constant
 
   V
Value: 368.0
Constant
 
pyruvate transport (2)
 
   Km
Value: 1.96
Constant
 
   V
Value: 200.0
Constant
 
phosphoglycerate kinase (6)
 
   Vmax_v11
Value: 2862.0
Constant
 
   KBPGA13_v11
Value: 0.003
Constant
 
   KADPg_v11
Value: 0.1
Constant
 
   r_v11
Value: 0.47
Constant
 
   KPGA3_v11
Value: 1.62
Constant
 
   KATPg_v11
Value: 0.29
Constant
 
pyruvate kinase (3)
 
   Vmax_v12
Value: 1020.0
Constant
 
   PK_n
Value: 2.5
Constant
 
   KADP_v12
Value: 0.114
Constant
 
atp utilisation (1)
 
   k
Value: 50.0
Constant
 
glycerol kinase (6)
 
   Vmax_v14
Value: 200.0
Constant
 
   KGly3Pg_v14
Value: 3.83
Constant
 
   KADPg_v14
Value: 0.56
Constant
 
   r_v14
Value: 60.86
Constant
 
   KGlycerol_v14
Value: 0.44
Constant
 
   KATPg_v14
Value: 0.24
Constant
 
phosphoglycerate mutase (4)
 
   Kms
Value: 0.27
Constant
 
   Kmp
Value: 0.11
Constant
 
   Vf
Value: 225.0
Constant
 
   Vr
Value: 495.0
Constant
 
enolase (4)
 
   Kms
Value: 0.054
Constant
 
   Kmp
Value: 0.24
Constant
 
   Vf
Value: 598.0
Constant
 
   Vr
Value: 394.68
Constant
 
adenylate kinase cytosol (2)
 
   k
Value: 1000000.0
Constant
 
   keqak
Value: 0.442
Constant
 
adenylate kinase glycosome (2)
 
   k
Value: 1000000.0
Constant
 
   keqak
Value: 0.442
Constant
 
3phosphoglycerate transport (2)
 
   k1
Value: 1000000.0
Constant
 
   k2
Value: 1000000.0
Constant
 
gly3p dhap antiporter (2)
 
   k1
Value: 1000000.0
Constant
 
   k2
Value: 1000000.0
Constant
 
glycerol transport (2)
 
   k1
Value: 1000000.0
Constant
 
   k2
Value: 1000000.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000211

Curator's comment: (updated: 28 Jan 2009 11:33:46 GMT)

The model reproduces Figure 5 of the original paper. The model was simulated using Copasi v.4.4.27.

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