Original Status:

Uncurated

Work done on model:

Went through paper, noted that of the 45 or so equations, some are the actual set of ODE's, some are constraints & conservation equations, and some are equations designed to find the 'steady state.' Basically, a group of equations was derived defining how all the enzyme rates would be calculated, and figures of 1.0 were put in. The equations were then allowed to equilibrate to find the actual parameters.

All the equations in the paper are coded into the model, and the model is overconstrained. Need to take out the equations that are not required and simply define the concentrations and rates that these equations work out, which are given in the paper. Unfortunately, it appears that not all of these parameters have actually been given. The model uses compartmentatlisation, and some concentrations are given for one compartment or the other.

The compartmentalisation is partially represented - there is some evidence of it in some equations in the CellML model, but not many of them. It is difficult to tell whether it has in fact been incorporated and the equations are mathematically equivalent.

To quote from the paper:

"The simulations were performed with the program MLAB (Civilized Software, Bethesda). First a time-dependent simulation was performed by integrating Equations 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 with a Gear-Adams algorithm, until the system approached a steady state. Usually the initial values of all independent variables were arbitrarily chosen to be 1. Subsequently, the system of nonlinear equations defining the steady state was solved with a Marquardt-Levenberg algorithm, to which the final metabolite concentrations of the time-dependent simulation were given as initial values. An imposed constraint was that all concentrations should be positive, and, if they were involved in a conserved moiety, they should be smaller than the corresponding conserved sum. Finally, starting from the obtained solution a second time integration was performed to test the stability of the steady state. It was examined whether the steady state was unique, by varying the initial metabolite concentrations over a wide range. This never gave a different steady state, but this cannot be considered definite proof of uniqueness."

Work required:

The differential equation set defined in this model can probably be coded successfully and may not take too long. It would probably be faster to use the original model as a base and use a text editor to delete much of it. The system of non-linear equations defining the steady state is currently not able to be implemented in any existing CellML simulation environment (as of the time of release of PCEnv 0.3)

Probably best to leave this model as it is until such time as it can be simulated by programs that use the CellML API.

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