Location: BG_cAMP @ 348913e60ceb / BG_cAMP_for_PDE.cellml

Author:
Shelley Fong <s.fong@auckland.ac.nz>
Date:
2021-06-21 16:30:43+12:00
Desc:
Codes to reproduce Saucerman Figs 2 and 3a
Permanent Source URI:
https://staging.physiomeproject.org/workspace/674/rawfile/348913e60cebcf090b62de195a8a13165b1512f7/BG_cAMP_for_PDE.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 -->
<model name="BG_cAMP" xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cellml="http://www.cellml.org/cellml/1.1#">
    <units name="per_sec">
        <unit exponent="-1" units="second"/>
    </units>
    <units name="J_per_K_per_mol">
        <unit units="joule"/>
        <unit exponent="-1" units="kelvin"/>
        <unit exponent="-1" units="mole"/>
    </units>
    <units name="C_per_mol">
        <unit units="coulomb"/>
        <unit exponent="-1" units="mole"/>
    </units>
    <units name="fmol">
        <unit prefix="femto" units="mole"/>
    </units>
    <units name="fmol_per_L">
        <unit prefix="femto" units="mole"/>
        <unit exponent="-1" units="litre"/>
    </units>
    <units name="fmol_per_L_per_sec">
        <unit units="fmol_per_L"/>
        <unit exponent="-1" units="second"/>
    </units>
    <units name="per_sec_per_fmol_per_L">
        <unit exponent="-1" units="second"/>
        <unit exponent="-1" units="fmol_per_L"/>
    </units>
    <units name="per_fmol">
        <unit exponent="-1" units="fmol"/>
    </units>
    <units name="fmol_per_sec">
        <unit units="fmol"/>
        <unit exponent="-1" units="second"/>
    </units>
    <units name="J_per_mol">
        <unit units="joule"/>
        <unit exponent="-1" units="mole"/>
    </units>
    <units name="mM">
        <unit prefix="milli" units="mole"/>
        <unit exponent="-1" units="litre"/>
    </units>
    <units name="uM">
        <unit prefix="micro" units="mole"/>
        <unit exponent="-1" units="litre"/>
    </units>
    <units name="mM_per_sec">
        <unit units="mM"/>
        <unit exponent="-1.0" units="second"/>
    </units>
    <units name="pL">
        <unit prefix="pico" units="litre"/>
    </units>
    <units name="m_to_u">
        <unit prefix="micro" units="second"/>
        <unit prefix="milli" units="second"/>
    </units>
    <component name="environment">
        <variable initial_value="0" name="t" units="second"/>
        <!-- Physical parameters-->
        <variable initial_value="8.31" name="R" units="J_per_K_per_mol"/>
        <variable initial_value="310" name="T" units="kelvin"/>
        <variable initial_value="96485" name="F" units="C_per_mol"/>
        <!-- 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>t</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-->
        <!-- ever-changing set of parameters-->
        <variable initial_value="7.83126e+06" name="kappa_1a" units="fmol_per_sec"/>
        <variable initial_value="1.52063e-05" name="kappa_1b" units="fmol_per_sec"/>
        <variable initial_value="5.37501e+06" name="kappa_2a" units="fmol_per_sec"/>
        <variable initial_value="0.00014504" name="kappa_2b" units="fmol_per_sec"/>
        <variable initial_value="4.98133e+09" name="kappa_3a" units="fmol_per_sec"/>
        <variable initial_value="5.79224e-19" name="kappa_3b" units="fmol_per_sec"/>
        <variable initial_value="706572" name="kappa_4a" units="fmol_per_sec"/>
        <variable initial_value="0.000905862" name="kappa_4b" units="fmol_per_sec"/>
        <variable initial_value="24.3859" name="kappa_5" units="fmol_per_sec"/>
        <variable initial_value="33.0947" name="kappa_6" units="fmol_per_sec"/>
        <variable initial_value="30670.7" name="kappa_7" units="fmol_per_sec"/>
        <variable initial_value="6.15713e-06" name="K_ATP" units="per_fmol"/>
        <variable initial_value="6.15713e-06" name="K_cAMP" units="per_fmol"/>
        <variable initial_value="0.00207391" name="K_AC" units="per_fmol"/>
        <variable initial_value="13152.4" name="K_AC_ATP" units="per_fmol"/>
        <variable initial_value="0.0302163" name="K_Gs_AC" units="per_fmol"/>
        <variable initial_value="58604.5" name="K_Gs_AC_ATP" units="per_fmol"/>
        <variable initial_value="3.26044e-05" name="K_FSK_AC" units="per_fmol"/>
        <variable initial_value="172.645" name="K_FSK_AC_ATP" units="per_fmol"/>
        <variable initial_value="0.689582" name="K_PDE" units="per_fmol"/>
        <variable initial_value="5519.61" name="K_PDE_cAMP" units="per_fmol"/>
        <variable initial_value="6.15713e-06" name="K_5AMP" units="per_fmol"/>
        <variable initial_value="5.9467" name="K_IBMX" units="per_fmol"/>
        <variable initial_value="4.10074" name="K_PDEinh" units="per_fmol"/>
        <variable initial_value="14.5698" name="K_Gs" units="per_fmol"/>
        <variable initial_value="0.0157212" name="K_FSK" units="per_fmol"/>
        <!-- States (and initial conditions)-->
        <!-- ORIGINAL-->
        <variable initial_value="1.90E-02" name="q_ATP" units="fmol"/>
        <variable initial_value="1.89E-3" name="q_AC" units="fmol"/>
        <variable initial_value="3.21E-02" name="q_cAMP" units="fmol"/>
        <!--                var q_AC: fmol {init: 1.89E-03};-->
        <variable initial_value="3.21E-02" name="q_cAMP_noPDE" units="fmol"/>
        <variable initial_value="1e-3" name="q_AC_ATP" units="fmol"/>
        <variable initial_value="1e-3" name="q_FSK" units="fmol"/>
        <variable initial_value="1e-3" name="q_FSK_AC" units="fmol"/>
        <variable initial_value="1e-3" name="q_FSK_AC_ATP" units="fmol"/>
        <variable initial_value="9.52E-04" name="q_Gs" units="fmol"/>
        <variable initial_value="1e-3" name="q_Gs_AC" units="fmol"/>
        <variable initial_value="1e-3" name="q_Gs_AC_ATP" units="fmol"/>
        <variable initial_value="1.48E-03" name="q_PDE" units="fmol"/>
        <variable initial_value="1e0" name="q_PDEinh" units="fmol"/>
        <variable initial_value="1e-16" name="q_PDE_cAMP" units="fmol"/>
        <variable initial_value="3.80E-02" name="q_IBMX" units="fmol"/>
        <variable initial_value="1e-1" name="q_5AMP" 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_Gs" units="J_per_mol"/>
        <variable name="mu_Gs_AC" units="J_per_mol"/>
        <variable name="mu_Gs_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_5AMP" 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_Gs" units="uM"/>
        <variable name="c_PDE" units="uM"/>
        <variable name="c_IBMX" units="uM"/>
        <variable name="c_5AMP" units="uM"/>
        <variable name="c_AC" units="uM"/>
        <variable name="c_AC_ATP" units="uM"/>
        <variable name="c_Gs_AC_ATP" units="uM"/>
        <variable name="c_Gs_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_Gs</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_Gs</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_5AMP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_5AMP</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_Gs_AC_ATP</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_Gs_AC_ATP</ci>
                    </apply>
                    <ci>vol</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>c_Gs_AC</ci>
                <apply>
                    <divide/>
                    <apply>
                        <times/>
                        <cn cellml:units="m_to_u" type="e-notation">1<sep/>3</cn>
                        <ci>q_Gs_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_Gs_AC_ATP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_Gs_AC_ATP</ci>
                            <ci>q_Gs_AC_ATP</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_Gs_AC</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_Gs_AC</ci>
                            <ci>q_Gs_AC</ci>
                        </apply>
                    </apply>
                </apply>
            </apply>
            <apply>
                <eq/>
                <ci>mu_Gs</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_Gs</ci>
                            <ci>q_Gs</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_5AMP</ci>
                <apply>
                    <times/>
                    <ci>R</ci>
                    <ci>T</ci>
                    <apply>
                        <ln/>
                        <apply>
                            <times/>
                            <ci>K_5AMP</ci>
                            <ci>q_5AMP</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_Gs_AC</ci>
                                    <ci>mu_ATP</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_Gs_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_Gs_AC_ATP</ci>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <apply>
                                    <plus/>
                                    <ci>mu_Gs_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_5AMP</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_Gs</ci>
                                </apply>
                                <apply>
                                    <times/>
                                    <ci>R</ci>
                                    <ci>T</ci>
                                </apply>
                            </apply>
                        </apply>
                        <apply>
                            <exp/>
                            <apply>
                                <divide/>
                                <ci>mu_Gs_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>
            <!-- saucerman: not all reactions are accounted for.-->
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_ATP</ci>
                </apply>
                <cn cellml:units="fmol_per_sec">0</cn>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_AC</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v6</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_AC_ATP</ci>
                </apply>
                <cn cellml:units="fmol_per_sec">0</cn>
            </apply>
            <!--                ode(q_AC_ATP, t) = v1a-v1b;-->
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_cAMP</ci>
                </apply>
                <apply>
                    <minus/>
                    <apply>
                        <plus/>
                        <ci>v1b</ci>
                        <ci>v2b</ci>
                        <ci>v3b</ci>
                    </apply>
                    <ci>v4a</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_cAMP_noPDE</ci>
                </apply>
                <apply>
                    <plus/>
                    <ci>v1b</ci>
                    <ci>v3b</ci>
                    <ci>v2b</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_FSK</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v7</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_FSK_AC</ci>
                </apply>
                <ci>v7</ci>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_FSK_AC_ATP</ci>
                </apply>
                <cn cellml:units="fmol_per_sec">0</cn>
            </apply>
            <!--                ode(q_FSK_AC_ATP, t) = v3a-v3b;-->
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_Gs</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v6</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_Gs_AC</ci>
                </apply>
                <ci>v6</ci>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_Gs_AC_ATP</ci>
                </apply>
                <cn cellml:units="fmol_per_sec">0</cn>
            </apply>
            <!--                ode(q_Gs_AC_ATP, t) = v2a-v2b;-->
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_PDE_cAMP</ci>
                </apply>
                <cn cellml:units="fmol_per_sec">0</cn>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_PDE</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v5</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_IBMX</ci>
                </apply>
                <apply>
                    <minus/>
                    <ci>v5</ci>
                </apply>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_PDEinh</ci>
                </apply>
                <ci>v5</ci>
            </apply>
            <apply>
                <eq/>
                <apply>
                    <diff/>
                    <bvar>
                        <ci>t</ci>
                    </bvar>
                    <ci>q_5AMP</ci>
                </apply>
                <ci>v4b</ci>
            </apply>
        </math>
        <!-- correct BG model
            ode(q_ATP, t) = -v1a-v3a-v2a;
        ode(q_AC, t) = v1b-v1a-v6-v7;
        ode(q_AC_ATP, t) = v1a-v1b;
        ode(q_cAMP, t) = v1b+v3b+v2b-v4a;
        ode(q_FSK, t) = -v7;
        ode(q_FSK_AC, t) = v7+v3b-v3a;
        ode(q_FSK_AC_ATP, t) = v3a-v3b;
        ode(q_Gs, t) = -v6;
        ode(q_Gs_AC, t) = v6-v2a+v2b;
        ode(q_Gs_AC_ATP, t) = v2a-v2b;
        ode(q_PDE_cAMP, t) = v4a-v4b;
        ode(q_PDE, t) = v4b-v4a-v5;
        ode(q_IBMX, t) = -v5;
        ode(q_PDEinh, t) = v5;
        ode(q_5AMP, t) = v4b;-->
        <!-- 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>
</model>