smallbone19

The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000380) Biomodels notes: The steady state concentration in Figure 18.4 of the reference publication has been reproduced here. The steady state concentration of the metabolites for 1) heat shock can be obtained by setting “heat=1” and 2) TPS1 mutant can be obtained by setting “heat=0” and by setting “activity=0.01” in the reaction T6P synthase. The model was simulated using Copasi v4.7 (Build 34). JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.

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Building a kinetic model of trehalose biosynthesis in Saccharomyces cerevisiae.

  • Kieran Smallbone
  • Naglis Malys
  • Hanan L Messiha
  • Jill A Wishart
  • Evangelos Simeonidis
Meth. Enzymol. 2011; 500 : 355-370
Abstract
In this chapter, we describe the steps needed to create a kinetic model of a metabolic pathway based on kinetic data from experimental measurements and literature review. Our methodology is presented by utilizing the example of trehalose metabolism in yeast. The biology of the trehalose cycle is briefly reviewed and discussed.

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
0.001 mole
60.0 second
0.001 mole litre^(-1.0)
0.016666666666666666 second^(-1.0)
1.6666666666666667e-05 mole litre^(-1.0) second^(-1.0)
1.0 dimensionless
Id Name Spatial dimensions Size
cell cell 3.0 1.0
medium medium 3.0 1.0
Id Name Initial quantity Compartment Fixed
adp ADP 1.282 cell (cell)
atp ATP 2.525 cell (cell)
f6p fructose 6-phosphate 0.625 cell (cell)
g1p glucose 1-phosphate 0.1 cell (cell)
g6p glucose 6-phosphate 2.675 cell (cell)
glc glucose 0.09675 cell (cell)
glx glucose 100.0 medium (medium)
h H+ 0.0 cell (cell)
h2o water 0.0 cell (cell)
pho phosphate 0.0 cell (cell)
ppi diphosphate 0.0 cell (cell)
t6p trehalose 6-phosphate 0.02 cell (cell)
trh trehalose 0.05 cell (cell)
udg UDP glucose 0.7 cell (cell)
udp UDP 0.2815 cell (cell)
utp UTP 0.6491 cell (cell)

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
glc = glc_0
g1p = g1p_0
g6p = g6p_0
trh = trh_0
t6p = t6p_0
udg = udg_0
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
hxk hexokinase glc + atp > g6p + adp + h

cell * pow(shock, heat) * Vmax / (Kglc * Katp) * (glc * atp - g6p * adp / Keq) / ((1 + glc / Kglc + g6p / Kg6p + t6p / Kit6p) * (1 + atp / Katp + adp / Kadp))
hxt glucose transport glx = glc

cell * pow(shock, heat) * Vmax * (glx - glc) / Kglc / (1 + (glx + glc) / Kglc + Ki * glx * glc / pow(Kglc, 2))
nth trehalase trh + h2o > {2.0}glc

cell * pow(shock, heat) * Vmax * trh / Ktrh / (1 + trh / Ktrh)
pgi G6P isomerase g6p = f6p

cell * pow(shock, heat) * Vmax / Kg6p * (g6p - f6p / Keq) / (1 + g6p / Kg6p + f6p / Kf6p)
pgm phosphoglucomutase g6p = g1p

cell * pow(shock, heat) * Vmax / Kg6p * (g6p - g1p / Keq) / (1 + g6p / Kg6p + g1p / Kg1p)
tpp T6P phosphatase t6p + h2o > trh + pho

cell * pow(shock, heat) * Vmax * t6p / Kt6p / (1 + t6p / Kt6p)
tps T6P synthase g6p + udg > t6p + udp + h

cell * activity * pow(shock, heat) * Vmax * g6p * udg / (Kg6p * Kudg) / ((1 + g6p / Kg6p) * (1 + udg / Kudg))
ugp UDP glucose phosphorylase g1p + utp + h > udg + ppi

cell * pow(shock, heat) * Vmax * utp * g1p / (Kutp * Kg1p) / (Kiutp / Kutp + utp / Kutp + g1p / Kg1p + utp * g1p / (Kutp * Kg1p) + Kiutp / Kutp * udg / Kiudg + g1p * udg / (Kg1p * Kiudg))

Global parameters

Id Value
g1p_0 0.1 mM
g1p_change <assignment rule> dimensionless
g6p_0 2.675 mM
g6p_change <assignment rule> dimensionless
glc_0 0.09765 mM
glc_change <assignment rule> dimensionless
heat 0.0 dimensionless
t6p_0 0.02 mM
t6p_change <assignment rule> dimensionless
trh_0 0.05 mM
trh_change <assignment rule> dimensionless
udg_0 0.7 mM
udg_change <assignment rule> dimensionless

Local parameters

Id Value Reaction
Vmax 1071.0 mM per min pgi (G6P isomerase)
Kg6p 1.4 mM pgi (G6P isomerase)
Kf6p 0.29 mM pgi (G6P isomerase)
Keq 0.3 dimensionless pgi (G6P isomerase)
shock 1.0 dimensionless pgi (G6P isomerase)
Vmax 97.24 mM per min hxt (glucose transport)
Kglc 1.1918 mM hxt (glucose transport)
Ki 0.91 dimensionless hxt (glucose transport)
shock 8.0 dimensionless hxt (glucose transport)
Vmax 289.6 mM per min hxk (hexokinase)
Kglc 0.08 mM hxk (hexokinase)
Katp 0.15 mM hxk (hexokinase)
Kg6p 30.0 mM hxk (hexokinase)
Kadp 0.23 mM hxk (hexokinase)
Keq 2000.0 dimensionless hxk (hexokinase)
Kit6p 0.04 mM hxk (hexokinase)
shock 8.0 dimensionless hxk (hexokinase)
Vmax 0.3545 mM per min pgm (phosphoglucomutase)
Kg6p 0.05 mM pgm (phosphoglucomutase)
Kg1p 0.023 mM pgm (phosphoglucomutase)
Keq 0.1667 dimensionless pgm (phosphoglucomutase)
shock 16.0 dimensionless pgm (phosphoglucomutase)
Vmax 6.5 mM per min tpp (T6P phosphatase)
Kt6p 0.5 mM tpp (T6P phosphatase)
shock 18.0 dimensionless tpp (T6P phosphatase)
Vmax 1.371 mM per min tps (T6P synthase)
Kg6p 3.8 mM tps (T6P synthase)
Kudg 0.886 mM tps (T6P synthase)
shock 12.0 dimensionless tps (T6P synthase)
activity 1.0 dimensionless tps (T6P synthase)
Vmax 15.2 mM per min nth (trehalase)
Ktrh 2.99 mM nth (trehalase)
shock 6.0 dimensionless nth (trehalase)
Vmax 36.82 mM per min ugp (UDP glucose phosphorylase)
Kutp 0.11 mM ugp (UDP glucose phosphorylase)
Kiutp 0.11 mM ugp (UDP glucose phosphorylase)
Kg1p 0.32 mM ugp (UDP glucose phosphorylase)
Kiudg 0.0035 mM ugp (UDP glucose phosphorylase)
shock 16.0 dimensionless ugp (UDP glucose phosphorylase)

Assignment rules

Definition
udg_change = log10(udg / udg_0)
t6p_change = log10(t6p / t6p_0)
trh_change = log10(trh / trh_0)
g6p_change = log10(g6p / g6p_0)
g1p_change = log10(g1p / g1p_0)
glc_change = log10(glc / glc_0)

Rate rules

Definition

Algebraic rules

Definition
Trigger Assignments