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BIOMD0000000266 - Voit2003 - Trehalose Cycle


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Reference Publication
Publication ID: 12782117
Voit EO.
Biochemical and genomic regulation of the trehalose cycle in yeast: review of observations and canonical model analysis.
J. Theor. Biol. 2003 Jul; 223(1): 55-78
Department of Biometry and Epidemiology, Medical University of South Carolina, 303K Cannon Place, 135 Cannon Street, Charleston, SC 29425, USA.  [more]
Original Model: BIOMD0000000266.origin
Submitter: Kieran Smallbone
Submission ID: MODEL1007210000
Submission Date: 21 Jul 2010 10:45:15 UTC
Last Modification Date: 22 Jun 2017 13:59:31 UTC
Creation Date: 20 Jul 2010 00:00:00 UTC
Encoders:  Lukas Endler
   Kieran Smallbone
set #1
bqbiol:hasTaxon Taxonomy Saccharomyces cerevisiae
bqbiol:isVersionOf Gene Ontology trehalose metabolic process
bqbiol:isPartOf KEGG Pathway Starch and sucrose metabolism - Saccharomyces cerevisiae (budding yeast)
bqbiol:hasPart Gene Ontology trehalose biosynthetic process
Gene Ontology glycogen biosynthetic process
bqbiol:hasVersion Gene Ontology modulation by symbiont of host response to heat
Voit2003 - Trehalose Cycle

This model is described in the article:

Voit EO.
J. Theor. Biol. 2003 Jul; 223(1): 55-78


The physiological hallmark of heat-shock response in yeast is a rapid, enormous increase in the concentration of trehalose. Normally found in growing yeast cells and other organisms only as traces, trehalose becomes a crucial protector of proteins and membranes against a variety of stresses, including heat, cold, starvation, desiccation, osmotic or oxidative stress, and exposure to toxicants. Trehalose is produced from glucose 6-phosphate and uridine diphosphate glucose in a two-step process, and recycled to glucose by trehalases. Even though the trehalose cycle consists of only a few metabolites and enzymatic steps, its regulatory structure and operation are surprisingly complex. The article begins with a review of experimental observations on the regulation of the trehalose cycle in yeast and proposes a canonical model for its analysis. The first part of this analysis demonstrates the benefits of the various regulatory features by means of controlled comparisons with models of otherwise equivalent pathways lacking these features. The second part elucidates the significance of the expression pattern of the trehalose cycle genes in response to heat shock. Interestingly, the genes contributing to trehalose formation are up-regulated to very different degrees, and even the trehalose degrading trehalases show drastically increased activity during heat-shock response. Again using the method of controlled comparisons, the model provides rationale for the observed pattern of gene expression and reveals benefits of the counterintuitive trehalase up-regulation.

To induce a heat shock, set the parameter heat_shock from 0 to 1. This changes the parameter values of X8 to X19 from 1 to the values given in table 3 of the original publication.
As this is an S-systems model, it does not contain any reactions encoded in SBML.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Publication ID: 12782117 Submission Date: 21 Jul 2010 10:45:15 UTC Last Modification Date: 22 Jun 2017 13:59:31 UTC Creation Date: 20 Jul 2010 00:00:00 UTC
Mathematical expressions
Assignment Rule (variable: flux_to_glucose) Assignment Rule (variable: flux_from_glucose) Rate Rule (variable: glucose) Assignment Rule (variable: flux_to_G6P)
Assignment Rule (variable: flux_from_G6P) Rate Rule (variable: G6P) Assignment Rule (variable: flux_to_G1P) Assignment Rule (variable: flux_from_G1P)
Rate Rule (variable: G1P) Assignment Rule (variable: flux_to_UDPG) Assignment Rule (variable: flux_from_UDPG) Rate Rule (variable: UDPG)
Assignment Rule (variable: flux_to_glycogen) Assignment Rule (variable: flux_from_glucogen) Rate Rule (variable: glycogen) Assignment Rule (variable: flux_to_T6P)
Assignment Rule (variable: flux_from_T6P) Rate Rule (variable: T6P) Assignment Rule (variable: flux_to_trehalose) Assignment Rule (variable: flux_from_trehalose)
Rate Rule (variable: trehalose) Assignment Rule (variable: glucose transport into cell) Assignment Rule (variable: hexokinase/glucokinase) Assignment Rule (variable: phosphofructokinase)
Assignment Rule (variable: G6P dehydrogenase) Assignment Rule (variable: phoshpoglucomutase) Assignment Rule (variable: phoshpoglucomutase) Assignment Rule (variable: UDPG pyrophosphorylase)
Assignment Rule (variable: glycogen synthase) Assignment Rule (variable: glycogen phosphorylase) Assignment Rule (variable: glycogen phosphorylase) Assignment Rule (variable: glycogen use)
Assignment Rule (variable: alpha,alpha-T6P synthase) Assignment Rule (variable: alpha,alpha--T6P phosphatase) Assignment Rule (variable: trehalase)  
Physical entities
Compartments Species
cell glucose G6P G1P
UDPG glycogen T6P
external glucose    
Global parameters
heat_shock glucose transport into cell hexokinase/glucokinase phosphofructokinase
G6P dehydrogenase phoshpoglucomutase phoshpoglucomutase UDPG pyrophosphorylase
glycogen synthase glycogen phosphorylase glycogen phosphorylase glycogen use
alpha,alpha-T6P synthase alpha,alpha--T6P phosphatase trehalase flux_to_glucose
flux_from_glucose flux_to_G6P flux_from_G6P flux_to_G1P
flux_from_G1P flux_to_UDPG flux_from_UDPG flux_to_glycogen
flux_from_glucogen flux_to_T6P flux_from_T6P flux_to_trehalose
Reactions (0)
Rules (35)
 Assignment Rule (name: flux_X1_in) flux_to_glucose = 31.912*X0^0.968*X2^-0.194*X7^0.00968*X8^0.968*X19^0.0323
 Assignment Rule (name: flux_X1_out) flux_from_glucose = 89.935*X1^0.75*X6^-0.4*X9
 Rate Rule (name: X1) d [ glucose] / d t= flux_X1_in-flux_X1_out
 Assignment Rule (name: flux_X2_in) flux_to_G6P = 142.72*X1^0.517*X2^-0.179*X3^0.183*X6^-0.276*X9^0.689*X12r^0.311
 Assignment Rule (name: flux_X2_out) flux_from_G6P = 30.12*X1^-0.00333*X2^0.575*X3^-0.17*X4^0.00333*X10^0.5111*X11^0.0667*X12f^0.411*X17^0.0111
 Rate Rule (name: X2) d [ G6P] / d t= flux_X2_in-flux_X2_out
 Assignment Rule (name: flux_X3_in) flux_to_G1P = 7.8819*X2^0.394*X3^-0.392*X4^-0.01*X5^0.0128*X12f^0.949*X15r^0.0513
 Assignment Rule (name: flux_X3_out) flux_from_G1P = 76.434*X2^-0.412*X3^0.593*X12r^0.718*X13^0.18*X15f^0.103
 Rate Rule (name: X3) d [ G1P] / d t= flux_X3_in-flux_X3_out
 Assignment Rule (name: flux_X4_in) flux_to_UDPG = 11.07*X3^0.5*X13
 Assignment Rule (name: flux_X4_out) flux_from_UDPG = 3.4556*X1^-0.0429*X2^0.214*X4^0.386*X14^0.857*X17^0.143
 Rate Rule (name: X4) d [ UDPG] / d t= flux_X4_in-flux_X4_out
 Assignment Rule (name: flux_X5_in) flux_to_glycogen = 11.06*X2^0.04*X3^0.32*X4^0.16*X14^0.6*X15f^0.4
 Assignment Rule (name: flux_X5_out) flux_from_glucogen = 4.929*X2^-0.04*X4^-0.04*X5^0.25*X15r^0.2*X16^0.8
 Rate Rule (name: X5) d [ glycogen] / d t= flux_X5_in-flux_X5_out
 Assignment Rule (name: flux_X6_in) flux_to_T6P = 0.19424*X1^-0.3*X2^0.3*X4^0.3*X17
 Assignment Rule (name: flux_X6_out) flux_from_T6P = 1.0939*X6^0.2*X18
 Rate Rule (name: X6) d [ T6P] / d t= flux_X6_in-flux_X6_out
 Assignment Rule (name: flux_X7_in) flux_to_trehalose = 1.0939*X6^0.2*X18
 Assignment Rule (name: flux_X7_out) flux_from_trehalose = 1.2288*X7^0.3*X19
 Rate Rule (name: X7) d [ trehalose] / d t= flux_X7_in-flux_X7_out
 Assignment Rule (name: X8) glucose transport into cell = piecewise(8, heat_shock == 1, 1)
 Assignment Rule (name: X9) hexokinase/glucokinase = piecewise(1, heat_shock == 8, 1)
 Assignment Rule (name: X10) phosphofructokinase = piecewise(1, heat_shock == 1, 1)
 Assignment Rule (name: X11) G6P dehydrogenase = piecewise(1, heat_shock == 6, 1)
 Assignment Rule (name: X12f) phoshpoglucomutase = piecewise(1, heat_shock == 16, 1)
 Assignment Rule (name: X12r) phoshpoglucomutase = piecewise(16, heat_shock == 1, 1)
 Assignment Rule (name: X13) UDPG pyrophosphorylase = piecewise(16, heat_shock == 1, 1)
 Assignment Rule (name: X14) glycogen synthase = piecewise(1, heat_shock == 16, 1)
 Assignment Rule (name: X15f) glycogen phosphorylase = piecewise(1, heat_shock == 50, 1)
 Assignment Rule (name: X15r) glycogen phosphorylase = piecewise(50, heat_shock == 1, 1)
 Assignment Rule (name: X16) glycogen use = piecewise(16, heat_shock == 1, 1)
 Assignment Rule (name: X17) alpha,alpha-T6P synthase = piecewise(1, heat_shock == 12, 1)
 Assignment Rule (name: X18) alpha,alpha--T6P phosphatase = piecewise(18, heat_shock == 1, 1)
 Assignment Rule (name: X19) trehalase = piecewise(1, heat_shock == 6, 1)
 cell Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: cell
Initial concentration: 0.03
Compartment: cell
Initial concentration: 1.0
Compartment: cell
Initial concentration: 0.1
Compartment: cell
Initial concentration: 0.7
Compartment: cell
Initial concentration: 1.0
Compartment: cell
Initial concentration: 0.02
Compartment: cell
Initial concentration: 0.05
 external Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: external
Initial concentration: 1.0
Global Parameters (29)
  glucose transport into cell
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: dimensionless)
  G6P dehydrogenase
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: dimensionless)
  UDPG pyrophosphorylase
Value: NaN   (Units: dimensionless)
  glycogen synthase
Value: NaN   (Units: dimensionless)
  glycogen phosphorylase
Value: NaN   (Units: dimensionless)
  glycogen phosphorylase
Value: NaN   (Units: dimensionless)
  glycogen use
Value: NaN   (Units: dimensionless)
  alpha,alpha-T6P synthase
Value: NaN   (Units: dimensionless)
  alpha,alpha--T6P phosphatase
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: dimensionless)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Value: NaN   (Units: mM per minute)
Representative curation result(s)
Representative curation result(s) of BIOMD0000000266

Curator's comment: (updated: 25 Aug 2010 14:13:20 BST)

Table of steady state concentrations and fluxes of the model with and without heat shock. The calculations were performed using Copasi.

The article does not give much quantitative data for the behavior under heat shock, the approximate fold changes of steady state concentrations can be found in section 5.2.1. "Biochemical consequences of heat shock" of the article.