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BIOMD0000000236 - Westermark2003_Pancreatic_GlycOsc_extended

 

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Reference Publication
Publication ID: 12829470
Westermark PO, Lansner A.
A model of phosphofructokinase and glycolytic oscillations in the pancreatic beta-cell.
Biophys. J. 2003 Jul; 85(1): 126-139
PSCI/SANS, NADA, Royal Institute of Technology (KTH), SE-100 44 Stockholm, Sweden. paal@nada.kth.se  [more]
Model
Original Model: BIOMD0000000236.xml.origin
Submitter: Lukas Endler
Submission ID: MODEL9574422639
Submission Date: 06 Aug 2009 17:00:26 UTC
Last Modification Date: 03 Jun 2014 14:56:48 UTC
Creation Date: 06 Aug 2009 16:54:12 UTC
Encoders:  Lukas Endler
   Vijayalakshmi Chelliah
   Paal O Westermark
set #1
bqbiol:isVersionOf Gene Ontology glycolytic process
set #2
bqbiol:isPartOf KEGG Pathway map00010
set #3
bqmodel:isDerivedFrom PubMed 6271617
set #4
bqbiol:isPartOf Reactome REACT_1383
set #5
bqbiol:hasTaxon Taxonomy Mammalia
Notes

This is the extended model described in eq. 2 of the article:
A model of phosphofructokinase and glycolytic oscillations in the pancreatic beta-cell.
Westermark PO and Lansner A. Biophys J. 2003 Jul;85(1):126-39. PMID: 12829470, doi:10.1016/S0006-3495(03)74460-9
Abstract:
We have constructed a model of the upper part of the glycolysis in the pancreatic beta-cell. The model comprises the enzymatic reactions from glucokinase to glyceraldehyde-3-phosphate dehydrogenase (GAPD). Our results show, for a substantial part of the parameter space, an oscillatory behavior of the glycolysis for a large range of glucose concentrations. We show how the occurrence of oscillations depends on glucokinase, aldolase and/or GAPD activities, and how the oscillation period depends on the phosphofructokinase activity. We propose that the ratio of glucokinase and aldolase and/or GAPD activities are adequate as characteristics of the glucose responsiveness, rather than only the glucokinase activity. We also propose that the rapid equilibrium between different oligomeric forms of phosphofructokinase may reduce the oscillation period sensitivity to phosphofructokinase activity. Methodologically, we show that a satisfying description of phosphofructokinase kinetics can be achieved using the irreversible Hill equation with allosteric modifiers. We emphasize the use of parameter ranges rather than fixed values, and the use of operationally well-defined parameters in order for this methodology to be feasible. The theoretical results presented in this study apply to the study of insulin secretion mechanisms, since glycolytic oscillations have been proposed as a cause of oscillations in the ATP/ADP ratio which is linked to insulin secretion.

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: 12829470 Submission Date: 06 Aug 2009 17:00:26 UTC Last Modification Date: 03 Jun 2014 14:56:48 UTC Creation Date: 06 Aug 2009 16:54:12 UTC
Mathematical expressions
Reactions
vgk vpfk vfba vgapdh
Rules
Assignment Rule (variable: sigma) Assignment Rule (variable: Vgk) Assignment Rule (variable: Vpfk) Assignment Rule (variable: Vfba)
Assignment Rule (variable: Vgapdh) Assignment Rule (variable: fructose-6-phosphate) Assignment Rule (variable: glyceraldehyde--phosphate) Assignment Rule (variable: dihydroxyacetone-phosphate)
Physical entities
Compartments Species
cell intracellular glucose G6P_F6P fructose-6-phosphate
fructose-1,6-biphosphate glyceraldehyde--phosphate dihydroxyacetone-phosphate
DHAP-G3P pool    
Global parameters
Vgk hGK KeqGPI KeqTPI
Vpfk Vfba Vgapdh Sgk
Spfk Sfba Sgapdh Xpfk
alpha hx hpfk hact
dw_per_ml min_to_sec Vgk_min Vpfk_min
Vfba_min Vgapdh_min Pfba Qfba
KeqFBA sigma    
Reactions (4)
 
 vgk [intracellular glucose] ↔ [G6P_F6P];  
 
 vpfk [G6P_F6P] ↔ [fructose-1,6-biphosphate];   {fructose-6-phosphate}
 
 vfba [fructose-1,6-biphosphate] ↔ 2.0 × [DHAP-G3P pool];   {glyceraldehyde--phosphate} , {dihydroxyacetone-phosphate}
 
 vgapdh [DHAP-G3P pool] → ;   {glyceraldehyde--phosphate}
 
Rules (8)
 
 Assignment Rule (name: sigma) sigma = F6P/Spfk
 
 Assignment Rule (name: Vgk) Vgk = Vgk_min*dw_per_ml/min_to_sec
 
 Assignment Rule (name: Vpfk) Vpfk = Vpfk_min*dw_per_ml/min_to_sec
 
 Assignment Rule (name: Vfba) Vfba = Vfba_min*dw_per_ml/min_to_sec
 
 Assignment Rule (name: Vgapdh) Vgapdh = Vgapdh_min*dw_per_ml/min_to_sec
 
 Assignment Rule (name: F6P) fructose-6-phosphate = G6P_F6P*KeqGPI/(1+KeqGPI)
 
 Assignment Rule (name: G3P) glyceraldehyde--phosphate = DHAP_G3P*KeqTPI/(1+KeqTPI)
 
 Assignment Rule (name: DHAP) dihydroxyacetone-phosphate = DHAP_G3P-G3P
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 intracellular glucose
Compartment: cell
Initial concentration: 10.0
Constant
 
 G6P_F6P
Compartment: cell
Initial concentration: 3.71728
 
  fructose-6-phosphate
Compartment: cell
 
 fructose-1,6-biphosphate
Compartment: cell
Initial concentration: 6.3612E-4
 
  glyceraldehyde--phosphate
Compartment: cell
 
  dihydroxyacetone-phosphate
Compartment: cell
 
 DHAP-G3P pool
Compartment: cell
Initial concentration: 0.00262966
 
Global Parameters (26)
 
   Vgk
Value: NaN   (Units: mM per sec)
 
   hGK
Value: 1.7   (Units: dimensionless)
Constant
 
   KeqGPI
Value: 0.3   (Units: dimensionless)
Constant
 
   KeqTPI
Value: 0.045455   (Units: dimensionless)
Constant
 
   Vpfk
Value: NaN   (Units: mM per sec)
 
   Vfba
Value: NaN   (Units: mM per sec)
 
   Vgapdh
Value: NaN   (Units: mM per sec)
 
   Sgk
Value: 8.0   (Units: mM)
Constant
 
   Spfk
Value: 4.0   (Units: mM)
Constant
 
   Sfba
Value: 0.0050   (Units: mM)
Constant
 
   Sgapdh
Value: 0.0050   (Units: mM)
Constant
 
   Xpfk
Value: 0.01   (Units: mM)
Constant
 
   alpha
Value: 5.0   (Units: dimensionless)
Constant
 
   hx
Value: 2.5   (Units: dimensionless)
Constant
 
   hpfk
Value: 2.5   (Units: dimensionless)
Constant
 
   hact
Value: 1.0   (Units: dimensionless)
Constant
 
   dw_per_ml
Value: 0.3333   (Units: gramm per ml)
Constant
 
   min_to_sec
Value: 60.0   (Units: dimensionless)
Constant
 
   Vgk_min
Value: 10.0   (Units: mmole per (min kg))
Constant
 
   Vpfk_min
Value: 100.0   (Units: mmole per (min kg))
Constant
 
   Vfba_min
Value: 25.0   (Units: mmole per (min kg))
Constant
 
   Vgapdh_min
Value: 250.0   (Units: mmole per (min kg))
Constant
 
   Pfba
Value: 0.5   (Units: mM)
Constant
 
   Qfba
Value: 0.275   (Units: mM)
Constant
 
   KeqFBA
Value: 0.1   (Units: mM)
Constant
 
   sigma
Value: NaN
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000236

Curator's comment: (updated: 26 Nov 2009 13:28:29 GMT)

The model reproduces figure 5a and 5b of the reference publication. The model was integrated and simulated using Copasi v4.5 (Build 30).

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