// Created by libAntimony v2.8.0
model *Rehm2006_Caspase()
// Compartments and Species:
compartment cell, mito;
species PC3 in cell, XIAP in cell, C9 in cell, PC9 in cell, C3 in cell;
species C9P in cell, XIAP_C3 in cell, XIAP_C9 in cell, XIAP_C9_C3 in cell;
species XIAP_p2frag in cell, XIAP_p2frag_C3 in cell, BIR12 in cell, BIR12_C3 in cell;
species BIR3R in cell, BIR3R_C9 in cell, BIR3R_p2frag in cell, XIAP_2SMAC in cell;
species BIR12_SMAC in cell, BIR3R_SMAC in cell, SMAC in cell, APAF1 in cell;
species XIAP_p2frag_2SMAC in cell, Substrate in cell, ClvgPrds in cell;
species SMAC_mito in mito, CytC_mit in mito, CytC_cell in cell;
// Assignment Rules:
apo_lim := piecewise(PC9, PC9 < APAF1, APAF1);
SMAC_norm := SMAC/XIAP_ini;
XIAP_2SMAC_norm := XIAP_2SMAC/XIAP_ini;
C9norm := C9/C9_tot;
C9Pnorm := C9P/C9_tot;
C3norm := C3/C3_tot;
PC3norm := PC3/C3_tot;
SMAC_rel := 1 - SMAC_mito/SMAC_tot;
Apoform := 1 - PC9/C9_tot;
XIAP_norm := XIAP/XIAP_ini;
XIAP_C3_norm := (XIAP_C3 + XIAP_C9_C3)/XIAP_ini;
XIAP_C9_norm := (XIAP_C9 + XIAP_C9_C3)/XIAP_ini;
XIAP_p2frag_norm := (XIAP_p2frag + XIAP_p2frag_C3)/XIAP_ini;
BIR12_norm := BIR12/XIAP_ini;
BIR3R_norm := BIR3R/XIAP_ini;
BIR12_C3_norm := BIR12_C3/XIAP_ini;
BIR3R_C9_norm := BIR3R_C9/XIAP_ini;
BIR3R_p2frag_norm := BIR3R_p2frag/XIAP_ini;
// Reactions:
reaction1: -> PC3; cell*(k1 - k1r*PC3);
reaction2: -> XIAP; cell*(k2 - k2r*XIAP);
reaction3: C9 + PC3 -> C3 + C9; cell*k3*C9*PC3;
reaction4: C9 + C3 -> C9P + C3; cell*k4*C9*C3;
reaction5: C9P + PC3 -> C9P + C3; cell*k5*C9P*PC3;
reaction6: PC3 + C3 -> 2C3; cell*k6*PC3*C3;
reaction7: C3 + XIAP -> XIAP_C3; cell*(k7*C3*XIAP - k7r*XIAP_C3);
reaction8: C3 + XIAP_C9 -> XIAP_C9_C3; cell*(k8*C3*XIAP_C9 - k8r*XIAP_C9_C3);
reaction9: C3 + XIAP_p2frag -> XIAP_p2frag_C3; cell*(k9*C3*XIAP_p2frag - k9r*XIAP_p2frag_C3);
reaction10: C3 + BIR12 -> BIR12_C3; cell*(k10*C3*BIR12 - k10r*BIR12_C3);
reaction11: C3 + XIAP -> BIR12 + BIR3R + C3; cell*k11*C3*XIAP;
reaction12: C3 + XIAP_C9 -> BIR12 + BIR3R_C9 + C3; cell*k12*C3*XIAP_C9;
reaction13: C3 + XIAP_C3 -> C3 + BIR12_C3 + BIR3R; cell*k13*C3*XIAP_C3;
reaction14: C3 + XIAP_p2frag -> C3 + BIR12 + BIR3R_p2frag; cell*k14*C3*XIAP_p2frag;
reaction15: C3 + XIAP_p2frag_C3 -> C3 + BIR12_C3 + BIR3R_p2frag; cell*k15*C3*XIAP_p2frag_C3;
reaction16: C3 + XIAP_C9_C3 -> C3 + BIR12_C3 + BIR3R_C9; cell*k16*C3*XIAP_C9_C3;
reaction17: C3 + XIAP_2SMAC -> C3 + BIR12_SMAC + BIR3R_SMAC; cell*k17*C3*XIAP_2SMAC;
reaction18: C3 + XIAP_C9_C3 -> C3 + C9P + XIAP_p2frag_C3; cell*k18*C3*XIAP_C9_C3;
reaction19: C3 + XIAP_C9 -> C3 + C9P + XIAP_p2frag; cell*k19*C3*XIAP_C9;
reaction20: C3 + BIR3R_C9 -> C3 + BIR3R_p2frag + C9P; cell*k20*C3*BIR3R_C9;
reaction21: C9 + XIAP -> XIAP_C9; cell*(k21*C9*XIAP - k21r*XIAP_C9);
reaction22: C9 + XIAP_C3 -> XIAP_C9_C3; cell*(k22*C9*XIAP_C3 - k22r*XIAP_C9_C3);
reaction23: C9 + BIR3R -> BIR3R_C9; cell*(k23*C9*BIR3R - k23r*BIR3R_C9);
reaction24: BIR3R_p2frag -> BIR3R; cell*k24*BIR3R_p2frag;
reaction25: XIAP_p2frag -> XIAP; cell*k25*XIAP_p2frag;
reaction26: XIAP + 2SMAC -> XIAP_2SMAC; cell*(k26*XIAP*SMAC*SMAC - k26r*XIAP_2SMAC);
reaction27: XIAP_C9 + 2SMAC -> XIAP_2SMAC + C9; cell*(k27*XIAP_C9*SMAC*SMAC - k27r*XIAP_2SMAC*C9);
reaction28: XIAP_C3 + 2SMAC -> XIAP_2SMAC + C3; cell*(k28*XIAP_C3*SMAC*SMAC - k28r*XIAP_2SMAC*C3);
reaction29: XIAP_C9_C3 + 2SMAC -> XIAP_2SMAC + C3 + C9; cell*(k29*XIAP_C9_C3*SMAC*SMAC - k29r*XIAP_2SMAC*C3*C9);
reaction30: BIR12 + SMAC -> BIR12_SMAC; cell*(k30*BIR12*SMAC - k30r*BIR12_SMAC);
reaction31: BIR3R + SMAC -> BIR3R_SMAC; cell*(k31*BIR3R*SMAC - k31r*BIR3R_SMAC);
reaction32: BIR12_C3 + SMAC -> BIR12_SMAC + C3; cell*(k32*BIR12_C3*SMAC - k32r*BIR12_SMAC*C3);
reaction33: BIR3R_C9 + SMAC -> BIR3R_SMAC + C9; cell*(k33*BIR3R_C9*SMAC - k33r*BIR3R_SMAC*C9);
reaction34: XIAP_p2frag + 2SMAC -> XIAP_p2frag_2SMAC; cell*(k34*XIAP_p2frag*SMAC*SMAC - k34r*XIAP_p2frag_2SMAC);
reaction35: C9P -> ; cell*k35*C9P;
reaction36: C9 -> ; cell*k36*C9;
reaction37: C3 -> ; cell*k37*C3;
reaction38: XIAP_C3 -> ; cell*k38*XIAP_C3;
reaction39: XIAP_C9_C3 -> ; cell*k39*XIAP_C9_C3;
reaction40: XIAP_C9 -> ; cell*k40*XIAP_C9;
reaction41: XIAP_p2frag -> ; cell*k41*XIAP_p2frag;
reaction42: XIAP_p2frag_C3 -> ; cell*k42*XIAP_p2frag_C3;
reaction43: XIAP_p2frag_2SMAC -> ; cell*k43*XIAP_p2frag_2SMAC;
reaction44: XIAP_2SMAC -> ; cell*k44*XIAP_2SMAC;
reaction45: BIR12 -> ; cell*k45*BIR12;
reaction46: BIR3R -> ; cell*k46*BIR3R;
reaction47: BIR12_SMAC -> ; cell*k47*BIR12_SMAC;
reaction48: BIR3R_SMAC -> ; cell*k48*BIR3R_SMAC;
reaction49: BIR12_C3 -> ; cell*k49*BIR12_C3;
reaction50: BIR3R_C9 -> ; cell*k50*BIR3R_C9;
reaction51: BIR3R_p2frag -> ; cell*k51*BIR3R_p2frag;
reaction52: SMAC -> ; cell*k52*SMAC;
reaction53: C3 + Substrate -> C3 + ClvgPrds; cell*k53*C3*Substrate;
SMAC_release: SMAC_mito -> SMAC; (cell*SMAC_mito*ln(2))/th_SMAC;
Apo_formation: PC9 + APAF1 -> C9; (cell*apo_lim*ln(2))/th_Apop;
CytC_release: CytC_mit -> CytC_cell; (cell*CytC_mit*ln(2))/th_CytC;
// Events:
Production_Breakdown: at Substrate < S_breakdown: k1 = 0, k1r = 0, k2 = 0, k2r = 0, k38 = 0.0058, k39 = 0.0058, k40 = 0.0058, k43 = 0.0058, k44 = 0.0058, k46 = 0.0058, k48 = 0.0058, k50 = 0.0058, k51 = 0.0058;
// Species initializations:
PC3 = 0.12;
XIAP = 0.063;
C9 = 0;
PC9 = 0.03;
C3 = 0;
C9P = 0;
XIAP_C3 = 0;
XIAP_C9 = 0;
XIAP_C9_C3 = 0;
XIAP_p2frag = 0;
XIAP_p2frag_C3 = 0;
BIR12 = 0;
BIR12_C3 = 0;
BIR3R = 0;
BIR3R_C9 = 0;
BIR3R_p2frag = 0;
XIAP_2SMAC = 0;
BIR12_SMAC = 0;
BIR3R_SMAC = 0;
SMAC = 0;
APAF1 = 3.372;
XIAP_p2frag_2SMAC = 0;
Substrate = 1;
ClvgPrds = 0;
SMAC_mito = 0.126;
CytC_mit = 10;
CytC_cell = 0;
// Compartment initializations:
cell = 1;
mito = 1;
// Variable initializations:
S_breakdown = 0.01;
S_breakdown has uM;
k51 = 0.0347;
k51 has per_min;
k50 = 0.0058;
k50 has per_min;
k48 = 0.0347;
k48 has per_min;
k46 = 0.0347;
k46 has per_min;
k44 = 0.0347;
k44 has per_min;
k43 = 0.0347;
k43 has per_min;
k40 = 0.0347;
k40 has per_min;
k39 = 0.0347;
k39 has per_min;
k38 = 0.0347;
k38 has per_min;
k2r = 0.0116;
k2r has per_min;
k2 = 0.0007308;
k2 has uM_per_min;
k1r = 0.0039;
k1r has per_min;
k1 = 0.000468;
k1 has uM_per_min;
k3 = 6;
k3 has per_uM_per_min;
k4 = 12;
k4 has per_uM_per_min;
k5 = 48;
k5 has per_uM_per_min;
k6 = 2.4;
k6 has per_uM_per_min;
k7 = 156;
k7 has per_uM_per_min;
k7r = 0.144;
k7r has per_min;
k8 = 156;
k8 has per_uM_per_min;
k8r = 0.144;
k8r has per_min;
k9 = 156;
k9 has per_uM_per_min;
k9r = 0.144;
k9r has per_min;
k10 = 156;
k10 has per_uM_per_min;
k10r = 0.144;
k10r has per_min;
k11 = 12;
k11 has per_uM_per_min;
k12 = 12;
k12 has per_uM_per_min;
k13 = 12;
k13 has per_uM_per_min;
k14 = 12;
k14 has per_uM_per_min;
k15 = 12;
k15 has per_uM_per_min;
k16 = 12;
k16 has per_uM_per_min;
k17 = 12;
k17 has per_uM_per_min;
k18 = 12;
k18 has per_uM_per_min;
k19 = 12;
k19 has per_uM_per_min;
k20 = 12;
k20 has per_uM_per_min;
k21 = 156;
k21 has per_uM_per_min;
k21r = 0.144;
k21r has per_min;
k22 = 156;
k22 has per_uM_per_min;
k22r = 0.144;
k22r has per_min;
k23 = 156;
k23 has per_uM_per_min;
k23r = 0.144;
k23r has per_min;
k24 = 0;
k25 = 0;
k26 = 420;
k26 has per_uM2_per_min;
k26r = 0.133;
k26r has per_min;
k27 = 420;
k27 has per_uM2_per_min;
k27r = 156;
k27r has per_uM_per_min;
k28 = 420;
k28 has per_uM2_per_min;
k28r = 156;
k28r has per_uM_per_min;
k29 = 420;
k29 has per_uM2_per_min;
k29r = 156;
k29r has per_uM2_per_min;
k30 = 4.45;
k30 has per_uM_per_min;
k30r = 31.9;
k30r has per_min;
k31 = 0.33;
k31 has per_uM_per_min;
k31r = 14.2;
k31r has per_min;
k32 = 4.45;
k32 has per_uM_per_min;
k32r = 156;
k32r has per_uM_per_min;
k33 = 0.33;
k33 has per_uM_per_min;
k33r = 156;
k33r has per_uM_per_min;
k34 = 420;
k34 has per_uM2_per_min;
k34r = 156;
k34r has per_min;
k35 = 0.0058;
k35 has per_min;
k36 = 0.0058;
k36 has per_min;
k37 = 0.0058;
k37 has per_min;
k41 = 0.0058;
k41 has per_min;
k42 = 0.0347;
k42 has per_min;
k45 = 0.0058;
k45 has per_min;
k47 = 0.0058;
k47 has per_min;
k49 = 0.0058;
k49 has per_min;
k52 = 0.0058;
k52 has per_min;
k53 = 12;
k53 has per_uM_per_min;
th_SMAC = 7;
th_SMAC has time_unit;
apo_lim has uM;
th_Apop = 2.3;
th_Apop has time_unit;
th_CytC = 1.5;
th_CytC has time_unit;
SMAC_norm has dimensionless;
XIAP_ini = XIAP;
XIAP_ini has uM;
XIAP_2SMAC_norm has dimensionless;
C9norm has dimensionless;
C9_tot = PC9;
C9_tot has uM;
C9Pnorm has dimensionless;
C3norm has dimensionless;
C3_tot = PC3;
C3_tot has uM;
PC3norm has dimensionless;
SMAC_rel has dimensionless;
SMAC_tot = SMAC_mito;
SMAC_tot has uM;
Apoform has dimensionless;
XIAP_norm has dimensionless;
XIAP_C3_norm has dimensionless;
XIAP_C9_norm has dimensionless;
XIAP_p2frag_norm has dimensionless;
BIR12_norm has dimensionless;
BIR3R_norm has dimensionless;
BIR12_C3_norm has dimensionless;
BIR3R_C9_norm has dimensionless;
BIR3R_p2frag_norm has dimensionless;
CytC_tot = CytC_mit;
CytC_tot has uM;
APAF1_tot = APAF1;
APAF1_tot has uM;
// Other declarations:
var k51, k50, k48, k46, k44, k43, k40, k39, k38, k2r, k2, k1r, k1, apo_lim;
var SMAC_norm, XIAP_ini, XIAP_2SMAC_norm, C9norm, C9_tot, C9Pnorm, C3norm;
var C3_tot, PC3norm, SMAC_rel, SMAC_tot, Apoform, XIAP_norm, XIAP_C3_norm;
var XIAP_C9_norm, XIAP_p2frag_norm, BIR12_norm, BIR3R_norm, BIR12_C3_norm;
var BIR3R_C9_norm, BIR3R_p2frag_norm, CytC_tot, APAF1_tot;
const cell, mito, S_breakdown, k3, k4, k5, k6, k7, k7r, k8, k8r, k9, k9r;
const k10, k10r, k11, k12, k13, k14, k15, k16, k17, k18, k19, k20, k21;
const k21r, k22, k22r, k23, k23r, k24, k25, k26, k26r, k27, k27r, k28, k28r;
const k29, k29r, k30, k30r, k31, k31r, k32, k32r, k33, k33r, k34, k34r;
const k35, k36, k37, k41, k42, k45, k47, k49, k52, k53, th_SMAC, th_Apop;
const th_CytC;
// Unit definitions:
unit time_unit = 60 second;
unit substance = 1e-6 mole;
unit uM = 1e-6 mole / litre;
unit uM_per_min = 1e-6 mole / (litre * 60 second);
unit per_uM_per_min = litre / (1e-6 mole * 60 second);
unit per_uM2_per_min = litre^2 / ((1e-6 mole)^2 * 60 second);
unit per_min = 1 / 60 second;
// Display Names:
time_unit is "min";
substance is "micromole";
uM is "microM";
uM_per_min is "uM/min";
per_uM_per_min is "1/(uM*min)";
per_uM2_per_min is "1/(uM^2*min)";
per_min is "1/min";
mito is "mitochondrium";
PC3 is "ProCasp3";
C9 is "Casp9(p35-p12)";
PC9 is "ProCasp9";
C9P is "Casp9(p35-p10)";
XIAP_C3 is "XIAP-Casp3";
XIAP_C9 is "XIAP-Casp9";
XIAP_C9_C3 is "XIAP-Casp9-Casp3";
XIAP_p2frag is "XIAP-p2 fragment";
XIAP_p2frag_C3 is "XIAP-p2frag-Casp3";
BIR12_C3 is "BIR12-Casp3";
BIR3R_C9 is "BIR3R-Casp9";
BIR3R_p2frag is "BIR3R-p2frag";
XIAP_2SMAC is "XIAP-2*SMAC";
BIR12_SMAC is "BIR12-SMAC";
BIR3R_SMAC is "BIR3R-SMAC";
XIAP_p2frag_2SMAC is "XIAP-p2frag-2*SMAC";
Substrate is "Casp3 Substrate";
ClvgPrds is "Clevage Products";
SMAC_mito is "SMAC in mitochondrium";
CytC_mit is "Cytochrome C in mitochondrium";
CytC_cell is "cytosolic Cytochrome C";
th_SMAC is "t_SMAC_0.5";
apo_lim is "limiting factor for apoptosome formation";
th_Apop is "t_Apop_0.5";
SMAC_norm is "free SMAC per XIAP";
XIAP_ini is "initial XIAP conc";
XIAP_2SMAC_norm is "XIAP2*SMAC per XIAP";
C9norm is "normalised Casp-9";
C9_tot is "Caspase9 tot";
C9Pnorm is "normalised Casp9-P";
C3norm is "normalised Casp-3";
C3_tot is "Caspase3 tot";
PC3norm is "normalised Procasp-3";
SMAC_rel is "percent SMAC release";
SMAC_tot is "total SMAC";
Apoform is "percent Apoptosome formation";
reaction1 is "ProCaspase3 Production";
reaction2 is "XIAP Production";
end