// 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