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BIOMD0000000253 - Teusink1998_Glycolysis_TurboDesign

 

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Reference Publication
Publication ID: 9612078
Teusink B, Walsh MC, van Dam K, Westerhoff HV.
The danger of metabolic pathways with turbo design.
Trends Biochem. Sci. 1998 May; 23(5): 162-169
E. C. Slater Institute, BioCentrum Amsterdam, University of Amsterdam, The Netherlands.  [more]
Model
Original Model: BIOMD0000000253.origin
Submitter: Kieran Smallbone
Submission ID: MODEL1007200002
Submission Date: 20 Jul 2010 19:28:53 UTC
Last Modification Date: 02 Dec 2010 22:45:30 UTC
Creation Date: 20 Jul 2010 00:00:00 UTC
Encoders:  Kieran Smallbone
set #1
bqbiol:isVersionOf KEGG Pathway Glycolysis / Gluconeogenesis - Saccharomyces cerevisiae (budding yeast)
bqbiol:isHomologTo Reactome REACT_1383
bqbiol:occursIn Taxonomy Saccharomyces cerevisiae
set #2
bqbiol:isVersionOf Gene Ontology glycolytic process
Notes

This is the model described in the article:
The danger of metabolic pathways with turbo design
Teusink B, Walsh MC, van Dam K, Westerhoff HV Trends Biochem. Sci. 1998 May; Volume: 23 (Issue: 5 ): 162-9 9612078 ,
Abstract:
Many catabolic pathways begin with an ATP-requiring activation step, after which further metabolism yields a surplus of ATP. Such a 'turbo' principle is useful but also contains an inherent risk. This is illustrated by a detailed kinetic analysis of a paradoxical Saccharomyces cerevisiae mutant; the mutant fails to grow on glucose because of overactive initial enzymes of glycolysis, but is defective only in an enzyme (trehalose 6-phosphate synthase) that appears to have little relevance to glycolysis. The ubiquity of pathways that possess an initial activation step, suggests that there might be many more genes that, when deleted, cause rather paradoxical regulation phenotypes (i.e. growth defects caused by enhanced utilization of growth substrate).

The model represents the wild-type cell: 'guarded' glycolysis, which is the inhibition of the HK module by hexose monophosphate. The model reproduces figures 3c and 3d of the reference publication.

To reproduce unguarded glycolysis, set parameter wild_type to '0'.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 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: 9612078 Submission Date: 20 Jul 2010 19:28:53 UTC Last Modification Date: 02 Dec 2010 22:45:30 UTC Creation Date: 20 Jul 2010 00:00:00 UTC
Mathematical expressions
Reactions
hexokinase phosphofructokinase lower ATPase
Rules
Assignment Rule (variable: trehalose 6-phosphate) Assignment Rule (variable: ADP) Assignment Rule (variable: lambda1) Assignment Rule (variable: lambda2)
Assignment Rule (variable: lambda3) Assignment Rule (variable: R) Assignment Rule (variable: T) Assignment Rule (variable: L)
Physical entities
Compartments Species
cell hexose monophosphate fructose 1,6-bisphosphate ATP
glucose trehalose 6-phosphate ADP
Global parameters
lambda1 lambda2 lambda3 R
T L KRHMP gR
c1 L0 KRATP gT
c2 KiATP ci  
Reactions (4)
 
 hexokinase [glucose] + [ATP] → [hexose monophosphate];   {trehalose 6-phosphate}
 
 phosphofructokinase [hexose monophosphate] + [ATP] → [fructose 1,6-bisphosphate];  
 
 lower [fructose 1,6-bisphosphate] + 4.0 × [ADP] → 4.0 × [ATP];  
 
 ATPase [ATP] → [ADP];  
 
Rules (8)
 
 Assignment Rule (name: Tre6P) trehalose 6-phosphate = HMP^2
 
 Assignment Rule (name: ADP) ADP = 5-ATP
 
 Assignment Rule (name: lambda1) lambda1 = HMP/KRHMP
 
 Assignment Rule (name: lambda2) lambda2 = ATP/KRATP
 
 Assignment Rule (name: lambda3) lambda3 = ATP/KiATP
 
 Assignment Rule (name: R) R = 1+lambda1+lambda2+gR*lambda1*lambda2
 
 Assignment Rule (name: T) T = 1+c1*lambda1+c2*lambda2+gT*c1*lambda1*c2*lambda2
 
 Assignment Rule (name: L) L = L0*((1+ci*lambda3)/(1+lambda3))^2
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 hexose monophosphate
Compartment: cell
Initial concentration: 0.1
 
 fructose 1,6-bisphosphate
Compartment: cell
Initial concentration: 1.0
 
 ATP
Compartment: cell
Initial concentration: 4.0
 
 glucose
Compartment: cell
Initial concentration: 10.0
 
  trehalose 6-phosphate
Compartment: cell
 
  ADP
Compartment: cell
 
Global Parameters (15)
 
   lambda1
Value: NaN
 
   lambda2
Value: NaN
 
   lambda3
Value: NaN
 
   R
Value: NaN
 
   T
Value: NaN
 
   L
Value: NaN
 
 KRHMP
Value: 1.0   (Units: mM)
Constant
 
   gR
Value: 10.0
Constant
 
   c1
Value: 5.0E-4
Constant
 
   L0
Value: 1000.0
Constant
 
 KRATP
Value: 0.06   (Units: mM)
Constant
 
   gT
Value: 1.0
Constant
 
   c2
Value: 1.0
Constant
 
 KiATP
Value: 10.0   (Units: mM)
Constant
 
   ci
Value: 10.0
Constant
 
hexokinase (5)
 
 VHK
Value: 68.0   (Units: mM per min)
Constant
 
 KATP
Value: 0.15   (Units: mM)
Constant
 
 KGlc
Value: 1.0   (Units: mM)
Constant
 
 KiTre6P
Value: 4.422   (Units: mM)
Constant
 
   wild_type
Value: 1.0   (Units: dimensionless)
Constant
 
phosphofructokinase (1)
 
 VPFK
Value: 30.0   (Units: mM per min)
Constant
 
lower (3)
 
 Vlower
Value: 20.0   (Units: mM per min)
Constant
 
 KFru16P2
Value: 1.0   (Units: mM)
Constant
 
 KADP
Value: 0.1   (Units: mM)
Constant
 
ATPase (2)
 
 VATPase
Value: 68.0   (Units: mM per min)
Constant
 
 KATP
Value: 3.0   (Units: mM)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000253

Curator's comment: (updated: 21 Jul 2010 13:48:00 BST)

The model represents the wild-type cell: 'guarded' glycolysis, which is the inhibition of the HK module by hexose monophosphate and reproduces figures 3c and 3d. The model was integrated and simulated using Copasi v4.5.31.

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