Location: BG_cAMP @ 3b4e9b848bf3 / BG_cAMP.cellml

Author:
Shelley Fong <s.fong@auckland.ac.nz>
Date:
2021-08-25 09:46:43+12:00
Desc:
Adding volume arguments and changing dimensions of input kinetic parameters to uM (source literature)
Permanent Source URI:
https://staging.physiomeproject.org/workspace/674/rawfile/3b4e9b848bf30fcd926aacbdcf226d68ad15e0de/BG_cAMP.cellml

<?xml version='1.0' encoding='UTF-8'?>
<!-- BG model of cAMP, based on saucerman2003, v1
 20may21 initialising file 
 24may21: basal reaction with AC. 
 given Km and kcat for kinetic versions of enzyme reaction, recreate BG parameters by setting k1+ = 1, k2+ = 0, K_E = 1 to be able to solve for K_S, K_C, kappa1 and kappa2 
 See Pan thesis section 4.2 
 21 Jul 21: constraint of cAMP to 5AMP using gibbs free energy from literature-->
<model name="BG_cAMP" xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cellml="http://www.cellml.org/cellml/1.1#" xmlns:xlink="http://www.w3.org/1999/xlink">
    <import xlink:href="units_and_constants/units_BG.cellml">
        <units name="per_sec" units_ref="per_sec"/>
        <units name="J_per_K_per_mol" units_ref="J_per_K_per_mol"/>
        <units name="C_per_mol" units_ref="C_per_mol"/>
        <units name="fmol" units_ref="fmol"/>
        <units name="fmol_per_L" units_ref="fmol_per_L"/>
        <units name="fmol_per_L_per_sec" units_ref="fmol_per_L_per_sec"/>
        <units name="per_sec_per_fmol_per_L" units_ref="per_sec_per_fmol_per_L"/>
        <units name="per_fmol" units_ref="per_fmol"/>
        <units name="fmol_per_sec" units_ref="fmol_per_sec"/>
        <units name="J_per_mol" units_ref="J_per_mol"/>
        <units name="mM" units_ref="mM"/>
        <units name="uM" units_ref="uM"/>
        <units name="mM_per_sec" units_ref="mM_per_sec"/>
        <units name="uM_per_sec" units_ref="uM_per_sec"/>
        <units name="pL" units_ref="pL"/>
        <units name="m_to_u" units_ref="m_to_u"/>
    </import>
    <import xlink:href="units_and_constants/constants_BG.cellml">
        <component component_ref="constants" name="constants"/>
    </import>
    <component name="environment">
        <variable name="time" public_interface="out" units="second"/>
    </component>
    <component name="cAMP">
        <variable name="time" public_interface="in" units="second"/>
        <!-- Physical parameters-->
        <variable name="R" public_interface="in" units="J_per_K_per_mol"/>
        <variable name="T" public_interface="in" units="kelvin"/>
        <!-- kinetic parameters - for comparing. (basal reaction)-->
        <variable initial_value="1.03e0" name="Km_basal_mM" units="mM"/>
        <variable initial_value="1.03e12" name="Km_basal" units="fmol_per_L"/>
        <variable initial_value="1e-12" name="k1p_basal" units="per_sec_per_fmol_per_L"/>
        <variable initial_value="0.83" name="k1m_basal" units="per_sec"/>
        <variable initial_value="0.2" name="k2p_basal" units="per_sec"/>
        <variable initial_value="2.41e-13" name="k2m_basal" units="per_sec_per_fmol_per_L"/>
        <variable initial_value="49.7e-6" name="AC_tot" units="mM"/>
        <variable initial_value="0.00263157894736842" name="ATP_kinetic" units="mM"/>
        <!-- kinetic states-->
        <variable initial_value="0.002631579" name="cAMP_kinetic" units="mM"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>cAMP_kinetic</ci>
                </apply>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <ci>k2p_basal</ci>
                        <ci>AC_tot</ci>
                        <ci>ATP_kinetic</ci>
                    </apply>
                    <apply>
                        <plus/>
                        <ci>Km_basal_mM</ci>
                        <ci>ATP_kinetic</ci>
                    </apply>
                </apply>
            </apply>
        </math>
        <!-- Bond graph parameters, found using pinv of kinetic parameters-->
        <!-- 21ju121 with fastKineticConstant = 1e6 and FSK andf dGibbs for rxn 4-->
        <variable initial_value="1.44613e+06" name="kappa_1a" units="fmol_per_sec"/>
        <variable initial_value="0.000301939" name="kappa_1b" units="fmol_per_sec"/>
        <variable initial_value="94062" name="kappa_2a" units="fmol_per_sec"/>
        <variable initial_value="0.0253818" name="kappa_2b" units="fmol_per_sec"/>
        <variable initial_value="2.7132e+08" name="kappa_3a" units="fmol_per_sec"/>
        <variable initial_value="3.15488e-17" name="kappa_3b" units="fmol_per_sec"/>
        <variable initial_value="316229" name="kappa_4a" units="fmol_per_sec"/>
        <variable initial_value="1.21627" name="kappa_4b" units="fmol_per_sec"/>
        <variable initial_value="204.342" name="kappa_5" units="fmol_per_sec"/>
        <variable initial_value="761.387" name="kappa_6" units="fmol_per_sec"/>
        <variable initial_value="219620" name="kappa_7" units="fmol_per_sec"/>
        <variable initial_value="2.35306e-05" name="K_ATP" units="per_fmol"/>
        <variable initial_value="2.35306e-05" name="K_cAMP" units="per_fmol"/>
        <variable initial_value="23.0954" name="K_AC" units="per_fmol"/>
        <variable initial_value="19.2554" name="K_AC_ATP" units="per_fmol"/>
        <variable initial_value="38.18" name="K_GsT_AC" units="per_fmol"/>
        <variable initial_value="9.73504" name="K_GsT_AC_ATP" units="per_fmol"/>
        <variable initial_value="0.132364" name="K_FSK_AC" units="per_fmol"/>
        <variable initial_value="0.0921422" name="K_FSK_AC_ATP" units="per_fmol"/>
        <variable initial_value="113.566" name="K_PDE" units="per_fmol"/>
        <variable initial_value="0.119504" name="K_PDE_cAMP" units="per_fmol"/>
        <variable initial_value="2.35306e-05" name="K_five_AMP" units="per_fmol"/>
        <variable initial_value="0.00121382" name="K_IBMX" units="per_fmol"/>
        <variable initial_value="142.26" name="K_PDEinh" units="per_fmol"/>
        <variable initial_value="0.120142" name="K_GsT" units="per_fmol"/>
        <variable initial_value="3.78646e-06" name="K_FSK" units="per_fmol"/>
        <!-- States (and initial conditions)-->
        <!-- 29jun21 WORKS. original concs, but complexes = 1e-13 . -->
        <!--        var q_ATP: fmol {init: 1.90E-02};
        var q_AC: fmol {init: 1.89E-3};
        var q_cAMP: fmol {init: 3.21E-02};
        var q_cAMP_noPDE: fmol {init: 3.21E-02};
        var q_AC_ATP: fmol {init: 1e-13};
        var q_FSK: fmol {init: 1e-9};
        var q_FSK_AC: fmol {init: 1e-13};
        var q_FSK_AC_ATP: fmol {init: 1e-13};
        var q_GsT: fmol {init: 9.52E-04};
        var q_GsT_AC: fmol {init: 1e-13};
        var q_GsT_AC_ATP: fmol {init: 1e-13};
        var q_PDE: fmol {init: 1.48E-03};
        var q_PDEinh: fmol {init: 1e-13};
        var q_PDE_cAMP: fmol {init: 1e-18};
        var q_IBMX: fmol {init: 3.80E-06};
        var q_five_AMP: fmol {init: 1e-13};-->
        <!-- 8 Jul conserving all species and enzyme states - e.g. all AC-containing species sum to AC_tot (saucerman)-->
        <variable initial_value="189.99905570" name="q_ATP" units="fmol"/>
        <variable initial_value="0.0006143333" name="q_AC" units="fmol"/>
        <variable initial_value="0.0314042742" name="q_cAMP" units="fmol"/>
        <variable initial_value="0.0314042742" name="q_cAMP_noPDE" units="fmol"/>
        <variable initial_value="0.000614333" name="q_AC_ATP" units="fmol"/>
        <variable initial_value="0.0000126667" name="q_FSK" units="fmol"/>
        <variable initial_value="0.0000126667" name="q_FSK_AC" units="fmol"/>
        <variable initial_value="0.0000126667" name="q_FSK_AC_ATP" units="fmol"/>
        <variable initial_value="0.00031730" name="q_GsT" units="fmol"/>
        <variable initial_value="0.00031730" name="q_GsT_AC" units="fmol"/>
        <variable initial_value="0.00031730" name="q_GsT_AC_ATP" units="fmol"/>
        <variable initial_value="0.0007171258" name="q_PDE" units="fmol"/>
        <variable initial_value="1e-13" name="q_PDEinh" units="fmol"/>
        <variable initial_value="0.0007171258" name="q_PDE_cAMP" units="fmol"/>
        <variable initial_value="3.80E-06" name="q_IBMX" units="fmol"/>
        <variable initial_value="1e-18" name="q_five_AMP" units="fmol"/>
        <!-- Bond variables-->
        <variable name="v1a" units="fmol_per_sec"/>
        <variable name="v1b" units="fmol_per_sec"/>
        <variable name="v2a" units="fmol_per_sec"/>
        <variable name="v2b" units="fmol_per_sec"/>
        <variable name="v3a" units="fmol_per_sec"/>
        <variable name="v3b" units="fmol_per_sec"/>
        <variable name="v4a" units="fmol_per_sec"/>
        <variable name="v4b" units="fmol_per_sec"/>
        <variable name="v5" units="fmol_per_sec"/>
        <variable name="v6" units="fmol_per_sec"/>
        <variable name="v7" units="fmol_per_sec"/>
        <variable name="mu_ATP" units="J_per_mol"/>
        <variable name="mu_AC" units="J_per_mol"/>
        <variable name="mu_cAMP" units="J_per_mol"/>
        <variable name="mu_AC_ATP" units="J_per_mol"/>
        <variable name="mu_FSK" units="J_per_mol"/>
        <variable name="mu_FSK_AC" units="J_per_mol"/>
        <variable name="mu_FSK_AC_ATP" units="J_per_mol"/>
        <variable name="mu_GsT" units="J_per_mol"/>
        <variable name="mu_GsT_AC" units="J_per_mol"/>
        <variable name="mu_GsT_AC_ATP" units="J_per_mol"/>
        <variable name="mu_PDE" units="J_per_mol"/>
        <variable name="mu_PDEinh" units="J_per_mol"/>
        <variable name="mu_PDE_cAMP" units="J_per_mol"/>
        <variable name="mu_IBMX" units="J_per_mol"/>
        <variable name="mu_five_AMP" units="J_per_mol"/>
        <!-- Concentrations - for plotting-->
        <variable name="c_ATP" units="uM"/>
        <variable name="c_cAMP" units="uM"/>
        <variable name="c_cAMP_noPDE" units="uM"/>
        <variable name="c_FSK" units="uM"/>
        <variable name="c_GsT" units="uM"/>
        <variable name="c_PDE" units="uM"/>
        <variable name="c_IBMX" units="uM"/>
        <variable name="c_five_AMP" units="uM"/>
        <variable name="c_AC" units="uM"/>
        <variable name="c_AC_ATP" units="uM"/>
        <variable name="c_GsT_AC_ATP" units="uM"/>
        <variable name="c_GsT_AC" units="uM"/>
        <variable initial_value="38.0" name="vol" units="pL"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <ci>c_ATP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_ATP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_cAMP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_cAMP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_cAMP_noPDE</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_cAMP_noPDE</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_FSK</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_FSK</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_IBMX</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_IBMX</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_GsT</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_GsT</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_PDE</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_PDE</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_five_AMP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_five_AMP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_AC</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_AC</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_AC_ATP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_AC_ATP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_GsT_AC_ATP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_GsT_AC_ATP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_GsT_AC</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_GsT_AC</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <!-- Constitutive equations-->
            <apply>
                <eq/>
                <ci>mu_ATP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_ATP</ci>
                            <ci>q_ATP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_AC</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_AC</ci>
                            <ci>q_AC</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_cAMP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_cAMP</ci>
                            <ci>q_cAMP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_AC_ATP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_AC_ATP</ci>
                            <ci>q_AC_ATP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_FSK_AC</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_FSK_AC</ci>
                            <ci>q_FSK_AC</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_FSK</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_FSK</ci>
                            <ci>q_FSK</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_FSK_AC_ATP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_FSK_AC_ATP</ci>
                            <ci>q_FSK_AC_ATP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_GsT_AC_ATP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_GsT_AC_ATP</ci>
                            <ci>q_GsT_AC_ATP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_GsT_AC</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_GsT_AC</ci>
                            <ci>q_GsT_AC</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_GsT</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_GsT</ci>
                            <ci>q_GsT</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_PDE_cAMP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_PDE_cAMP</ci>
                            <ci>q_PDE_cAMP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_PDE</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_PDE</ci>
                            <ci>q_PDE</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_IBMX</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_IBMX</ci>
                            <ci>q_IBMX</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_PDEinh</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_PDEinh</ci>
                            <ci>q_PDEinh</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_five_AMP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_five_AMP</ci>
                            <ci>q_five_AMP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v1a</ci>
                <apply>
                    <times/>
                    <ci>kappa_1a</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_AC</ci>
                                    <ci>mu_ATP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v1b</ci>
                <apply>
                    <times/>
                    <ci>kappa_1b</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_AC</ci>
                                    <ci>mu_cAMP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v2a</ci>
                <apply>
                    <times/>
                    <ci>kappa_2a</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_GsT_AC</ci>
                                    <ci>mu_ATP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_GsT_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v2b</ci>
                <apply>
                    <times/>
                    <ci>kappa_2b</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_GsT_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_GsT_AC</ci>
                                    <ci>mu_cAMP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v3a</ci>
                <apply>
                    <times/>
                    <ci>kappa_3a</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_FSK_AC</ci>
                                    <ci>mu_ATP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_FSK_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v3b</ci>
                <apply>
                    <times/>
                    <ci>kappa_3b</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_FSK_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_FSK_AC</ci>
                                    <ci>mu_cAMP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v4a</ci>
                <apply>
                    <times/>
                    <ci>kappa_4a</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_PDE</ci>
                                    <ci>mu_cAMP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_PDE_cAMP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v4b</ci>
                <apply>
                    <times/>
                    <ci>kappa_4b</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_PDE_cAMP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_PDE</ci>
                                    <ci>mu_five_AMP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v5</ci>
                <apply>
                    <times/>
                    <ci>kappa_5</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_PDE</ci>
                                    <ci>mu_IBMX</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_PDEinh</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v6</ci>
                <apply>
                    <times/>
                    <ci>kappa_6</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_AC</ci>
                                    <ci>mu_GsT</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_GsT_AC</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>v7</ci>
                <apply>
                    <times/>
                    <ci>kappa_7</ci>
                    <apply>
                        <minus/>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_FSK</ci>
                                    <ci>mu_AC</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_FSK_AC</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                    </apply>
                </apply>
            </apply>
        </math>
        <!-- velocity in uM_per_sec-->
        <variable name="v1b_kinetic" units="uM_per_sec"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <ci>v1b_kinetic</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <ci>v1b</ci>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_ATP</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <minus/>
                        <apply>
                            <minus/>
                            <ci>v1a</ci>
                        </apply>
                        <ci>v3a</ci>
                    </apply>
                    <ci>v2a</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_AC</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <minus/>
                        <apply>
                            <minus/>
                            <ci>v1b</ci>
                            <ci>v1a</ci>
                        </apply>
                        <ci>v6</ci>
                    </apply>
                    <ci>v7</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_AC_ATP</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v1a</ci>
                    <ci>v1b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_cAMP</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <ci>v1b</ci>
                        <ci>v3b</ci>
                        <ci>v2b</ci>
                    </apply>
                    <ci>v4a</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_FSK</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v7</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_FSK_AC</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <ci>v7</ci>
                        <ci>v3b</ci>
                    </apply>
                    <ci>v3a</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_FSK_AC_ATP</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v3a</ci>
                    <ci>v3b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_GsT</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v6</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_GsT_AC</ci>
                </apply>
                <apply>
                    <plus/>
                    <apply>
                        <minus/>
                        <ci>v6</ci>
                        <ci>v2a</ci>
                    </apply>
                    <ci>v2b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_GsT_AC_ATP</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v2a</ci>
                    <ci>v2b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_PDE_cAMP</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v4a</ci>
                    <ci>v4b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_PDE</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <minus/>
                        <ci>v4b</ci>
                        <ci>v4a</ci>
                    </apply>
                    <ci>v5</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_IBMX</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v5</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_PDEinh</ci>
                </apply>
                <ci>v5</ci>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>time</ci>
                    </bvar>
                    <ci>q_five_AMP</ci>
                </apply>
                <ci>v4b</ci>
            </apply>
        </math>
        <!-- calculate velocity wrt changing concentration rate-->
        <variable name="PDE_ACT_4a" units="mM_per_sec"/>
        <variable name="PDE_ACT_4ab" units="mM_per_sec"/>
        <math xmlns="http://www.w3.org/1998/Math/MathML">
            <apply>
                <eq/>
                <ci>PDE_ACT_4a</ci>
                <apply>
                    <divide/>
                    <ci>v4a</ci>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>PDE_ACT_4ab</ci>
                <apply>
                    <divide/>
                    <apply>
                        <minus/>
                        <ci>v4a</ci>
                        <ci>v4b</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
        </math>
    </component>
    <connection>
        <map_components component_1="environment" component_2="cAMP"/>
        <map_variables variable_1="time" variable_2="time"/>
    </connection>
    <connection>
        <map_components component_1="constants" component_2="cAMP"/>
        <map_variables variable_1="R" variable_2="R"/>
        <map_variables variable_1="T" variable_2="T"/>
    </connection>
</model>