FCU_guanylylCyclase.cellml

About this model

This is a Functional cell Unit (FCU) of the action of the soluble guanylyl cyclase (sGC) enzyme in the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), following a stimulus from nitric oxide.

INPUTS:
  • Nitric oxide (NO)
OUTPUTS:
  • cGMP
REACTIONS:
  • Re1sGC: Transition of sGC from the basal state (EB) into an intermediate state (E6c) through NO binding
  • Re2sGC: Natural decay of E6c to active E5c state
  • Re3sGC: NO-dependent conversion of E6c into E5c
  • Re4sGC: Conversion of E5c to EB through NO dissociation
  • ReDNO: Consumption of NO by scavengers
  • Re1a and 1b: Production of cGMP from GTP by E5c
  • Re2a and 2b: Degradation of cGMP to GMP by phosphodiesterase-5 (PDE)

Model status

The current CellML implementation runs in OpenCOR.

Model overview

This model is based on existing kinetic model by Yang et. al. (2005), where the mathematics are translated into the bond-graph formalism. This describes the model in energetic terms and forces adherence to the laws of thermodynamics.

The bond graph networks for the two modules comprising this FCU are as follows:

sGCactivation

Fig. 1. sGC activation module

cGMP_metabolism

Fig. 2. cGMP production and degradation module

For the above bond-graphs, a '0' node refers to a junction where all chemical potentials are the same. A '1' node refers to all fluxes being the same going in and out of the junction.

List of chemical species
Abbreviation Name
sGC Guanylyl cyclase (soluble)
EB Basal variant of sGC
E6c Intermediate variant of sGC
E5c Active variant of sGC
cGMP Cyclic guanosine monophosphate
GMP Guanosine monophosphate
GTP Guanosine triphosphate
NO Nitric oxide
NOD Nitric oxide product (unavailable for this scheme)
PDE Phosphodiesterase-5

Parameter finding

A description of the process to find bond-graph parameters is shown in the folder parameter_finder, which relies on the:

  1. stoichiometry of system
  2. kinetic constants for forward/reverse reactions
  • If not already, all reactions are made reversible by assigning a small value to the reverse direction.
  1. linear algebra script.

Here, this solve process is performed in Python.

Interactions

This FCU may be coupled to the Hai-Murphy module of smooth muscle contraction, as adapted by Yang et. al, where cGMP acts as an input. The resulting CellML script is also provided in this workspace.