- Author:
- Shelley Fong <sfon036@UoA.auckland.ac.nz>
- Date:
- 2022-05-19 16:17:36+12:00
- Desc:
- Updating rst exposure
- Permanent Source URI:
- http://models.cellml.org/workspace/860/rawfile/942577618540797370e0ce9c50a4a186d171f6dc/exposure/exposure_frontpage.rst
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) <https://doi.org/10.1152/ajpheart.00216.2004>`_, 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:
.. figure:: exposure/sGCactivation.png
:width: 70%
:align: center
:alt: sGCactivation
Fig. 1. sGC activation module
.. figure:: exposure/cGMP_metabolism.png
:width: 100%
:align: center
:alt: 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.
.. csv-table:: List of chemical species
:header: "Abbreviation", "Name"
:widths: 5, 15
"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"
"NO\ :sub:`D`", "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 <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.
3. `linear algebra script <https://models.physiomeproject.org/workspace/860/file/753e301e529312d3092d054f6bceca72ca116f56/parameter_finder/find_BG_parameters_composite.py>`_.
Here, this solve process is performed in Python.
Interactions
~~~~~~~~~~~~
This FCU may be coupled to the `Hai-Murphy module <https://models.physiomeproject.org/workspace/818>`_ 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 <https://models.physiomeproject.org/workspace/860/file/753e301e529312d3092d054f6bceca72ca116f56/FCU_guanylylCyclase_withSM.cellml>`_.
Original kinetic model
======================
Yang et. al.: `Mathematical modeling of the nitric oxide/cGMP pathway in the vascular smooth muscle cell. <https://models.physiomeproject.org/workspace/562>`_
