//Created by libAntimony v2.4 model cloutier_2009a__environment(time_) // Variable initializations: time_ = ; end model cloutier_2009a__F6P(F6P, V_hk, V_pfk, V_pfk2, time_) // Rate Rules: F6P' = V_hk - (V_pfk - V_pfk2); // Variable initializations: F6P = 0.2; V_hk = ; V_pfk = ; V_pfk2 = ; time_ = ; end model cloutier_2009a__F26P(F26P, V_pfk2, time_) // Rate Rules: F26P' = V_pfk2; // Variable initializations: F26P = 0.001; V_pfk2 = ; time_ = ; end model cloutier_2009a__GAP(GAP, V_pk, V_pfk, time_) // Rate Rules: GAP' = 2.0 * V_pfk - V_pk; // Variable initializations: GAP = 0.0405; V_pk = ; V_pfk = ; time_ = ; end model cloutier_2009a__PYR(PYR, V_pk, V_ldh, V_op, time_) // Rate Rules: PYR' = V_pk - (V_op + V_ldh); // Variable initializations: PYR = 0.1; V_pk = ; V_ldh = ; V_op = ; time_ = ; end model cloutier_2009a__LAC(LAC, V_lac, V_ldh, time_) // Rate Rules: LAC' = 2.25 * V_ldh + V_lac; // Variable initializations: LAC = 0.5; V_lac = ; V_ldh = ; time_ = ; end model cloutier_2009a__ATP(ATP, V_hk, V_pfk, V_pfk2, V_pk, V_ATPase, V_op, V_ck, dAMP_dATP, time_) // Rate Rules: ATP' = ((2.0 * V_pk + 15.0 * V_op + V_ck) - (V_hk + V_pfk + V_pfk2 + V_ATPase)) * power(1 - dAMP_dATP, -1); // Variable initializations: ATP = 2.402; V_hk = ; V_pfk = ; V_pfk2 = ; V_pk = ; V_ATPase = ; V_op = ; V_ck = ; dAMP_dATP = ; time_ = ; end model cloutier_2009a__PCr(PCr, V_ck, time_) // Rate Rules: PCr' = - V_ck; // Variable initializations: PCr = 18.14; V_ck = ; time_ = ; end model cloutier_2009a__V_hk(V_hk, F6P, ATP) // Assignment Rules: V_hk := Vmax_hk * (ATP / (ATP + Km_ATP_hk)) * power(1 + power(F6P / KI_F6P, 4), -1); // Variable initializations: Vmax_hk = 2.5; Km_ATP_hk = 0.5; KI_F6P = 0.068; F6P = ; ATP = ; end model cloutier_2009a__V_pfk(V_pfk, ATP, F6P, F26P, AMP_act, ATP_inh) // Assignment Rules: V_pfk := Vmax_pfk * (F6P / (F6P + Km_F6P_pfk)) * (ATP / (ATP + Km_ATP_pfk)) * (F26P / (F26P + Km_F26P_pfk)) * ATP_inh * AMP_act; // Variable initializations: Vmax_pfk = 3.85; Km_ATP_pfk = 0.05; Km_F6P_pfk = 0.18; Km_F26P_pfk = 0.01; ATP = ; F6P = ; F26P = ; AMP_act = ; ATP_inh = ; end model cloutier_2009a__V_pfk2(V_pfk2, ATP, F6P, F26P, AMP_pfk2) // Assignment Rules: V_pfk2 := Vmaxf_pfk2 * (ATP / (ATP + Km_ATP_pfk2)) * (F6P / (F6P + Km_F6P_pfk2)) * AMP_pfk2 - Vmaxr_pfk2 * (F26P / (F26P + Km_F26P_pfk2)); // Variable initializations: Vmaxf_pfk2 = 0; Vmaxr_pfk2 = 0; Km_ATP_pfk2 = 0.05; Km_F6P_pfk2 = 0.01; Km_F26P_pfk2 = 0.0001; ATP = ; F6P = ; F26P = ; AMP_pfk2 = ; end model cloutier_2009a__V_pk(V_pk, ADP, GAP, ATP_inh) // Assignment Rules: V_pk := Vmax_pk * (GAP / (GAP + Km_GAP_pk)) * (ADP / (ADP + Km_ADP_pk)) * 0.1104; // Variable initializations: Vmax_pk = 5.0; Km_ADP_pk = 0.005; Km_GAP_pk = 0.4; ADP = ; GAP = ; ATP_inh = ; end model cloutier_2009a__V_op(V_op, ATP, ADP, PYR) // Assignment Rules: V_op := Vmax_op * (PYR / (PYR + Km_PYR_op)) * (ADP / (ADP + Km_ADP_op)) * (1 / (1 + 0.1 * 24)); // Variable initializations: Vmax_op = 1.0; Km_ADP_op = 0.005; Km_PYR_op = 0.5; ATP = ; ADP = ; PYR = ; end model cloutier_2009a__V_ldh(V_ldh, LAC, PYR) // Assignment Rules: V_ldh := kf_ldh * PYR - kr_ldh * LAC; // Variable initializations: kf_ldh = 0; kr_ldh = 0; LAC = ; PYR = ; end model cloutier_2009a__V_ck(V_ck, Cr, PCr, ADP, ATP) // Assignment Rules: V_ck := kf_ck * PCr * ADP - kr_ck * Cr * ATP; // Variable initializations: kf_ck = 0; kr_ck = 0; Cr = ; PCr = ; ADP = ; ATP = ; end model cloutier_2009a__Cr(Cr, PCr) // Assignment Rules: Cr := PCrtot - PCr; // Variable initializations: PCrtot = 20.0; PCr = ; end model cloutier_2009a__V_ATPase(V_ATPase, ATP, v_stim) // Assignment Rules: V_ATPase := Vmax_ATPase * (ATP / (ATP + Km_ATP)) * (1 + v_stim); // Variable initializations: Vmax_ATPase = 0.9355; Km_ATP = 0.5; ATP = ; v_stim = ; end model cloutier_2009a__V_lac(V_lac, LAC, v_stim) // Assignment Rules: V_lac := Vlac_0 * (1 + v_stim * K_LAC) - K_LAC_eff * LAC; // Variable initializations: Vlac_0 = 0.355; K_LAC_eff = 0.71; K_LAC = 0.641; LAC = ; v_stim = ; end model cloutier_2009a__ADP(ADP, u, ATP, ANP, Q_adk) // Assignment Rules: ADP := (ATP / 2) * (- Q_adk + root(u)); u := power(Q_adk, 2) + 4 * Q_adk * (ANP / ATP - 1); // Variable initializations: ATP = ; ANP = ; Q_adk = ; end model cloutier_2009a__dAMP_dATP(dAMP_dATP, ATP, ANP, u, Q_adk) // Assignment Rules: dAMP_dATP := -(1) + Q_adk / 2 + -(0.5 * root(u)) + Q_adk * (ANP / (ATP * root(u))); // Variable initializations: ATP = ; ANP = ; u = ; Q_adk = ; end model cloutier_2009a__AMP(AMP, ANP, ATP, ADP) // Assignment Rules: AMP := ANP - (ATP + ADP); // Variable initializations: ANP = ; ATP = ; ADP = ; end model cloutier_2009a__ATP_inh(ATP_inh, ATP) // Assignment Rules: ATP_inh := power((1 + nATP * (ATP / KI_ATP)) / (1 + ATP / KI_ATP), 4); // Variable initializations: nATP = 0.4; KI_ATP = 1.0; ATP = ; end model cloutier_2009a__AMP_act(AMP_act, AMP) // Assignment Rules: AMP_act := power((1 + AMP / Ka_AMP) / (1 + nAMP * (AMP / Ka_AMP)), 4); // Variable initializations: nAMP = 0.5; Ka_AMP = 0.05; AMP = ; end model cloutier_2009a__v_stim(v_stim, time_) // Assignment Rules: v_stim := stim * (v1_n + v2_n * ((time_ - to) / t_n_stim) * exp(-((time_ - to) * (unitpulseSB / t_n_stim)))) * unitpulseSB; unitpulseSB := piecewise( 1 , ( geq(time_, to)) && (time_ <= to + tend ), 0 ); // Variable initializations: stim = 1; to = 50; tend = 200; v1_n = 0.5; v2_n = 0.0; t_n_stim = 2; time_ = ; end model cloutier_2009a__model_parameters(ANP, Q_adk) // Variable initializations: ANP = 2.51; Q_adk = 0.92; end model cloutier_2009a__AMP_pfk2(AMP_pfk2, AMP) // Assignment Rules: AMP_pfk2 := power(AMP / Kamp_pfk2, nh_amp) / (1 + power(AMP / Kamp_pfk2, nh_amp)); // Variable initializations: Kamp_pfk2 = 0.005; nh_amp = 2; AMP = ; end model *cloutier_2009a____main() // Sub-modules, and any changes to those submodules: environment: cloutier_2009a__environment(time_); F6P: cloutier_2009a__F6P(F6P0, V_hk0, V_pfk0, V_pfk20, time_); F26P: cloutier_2009a__F26P(F26P0, V_pfk20, time_); GAP: cloutier_2009a__GAP(GAP0, V_pk0, V_pfk0, time_); PYR: cloutier_2009a__PYR(PYR0, V_pk0, V_ldh0, V_op0, time_); LAC: cloutier_2009a__LAC(LAC0, V_lac0, V_ldh0, time_); ATP: cloutier_2009a__ATP(ATP0, V_hk0, V_pfk0, V_pfk20, V_pk0, V_ATPase0, V_op0, V_ck0, dAMP_dATP0, time_); PCr: cloutier_2009a__PCr(PCr0, V_ck0, time_); V_hk: cloutier_2009a__V_hk(V_hk0, F6P0, ATP0); V_pfk: cloutier_2009a__V_pfk(V_pfk0, ATP0, F6P0, F26P0, AMP_act0, ATP_inh0); V_pfk2: cloutier_2009a__V_pfk2(V_pfk20, ATP0, F6P0, F26P0, AMP_pfk20); V_pk: cloutier_2009a__V_pk(V_pk0, ADP0, GAP0, ATP_inh0); V_op: cloutier_2009a__V_op(V_op0, ATP0, ADP0, PYR0); V_ldh: cloutier_2009a__V_ldh(V_ldh0, LAC0, PYR0); V_ck: cloutier_2009a__V_ck(V_ck0, Cr0, PCr0, ADP0, ATP0); Cr: cloutier_2009a__Cr(Cr0, PCr0); V_ATPase: cloutier_2009a__V_ATPase(V_ATPase0, ATP0, v_stim0); V_lac: cloutier_2009a__V_lac(V_lac0, LAC0, v_stim0); ADP: cloutier_2009a__ADP(ADP0, u, ATP0, ANP, Q_adk); dAMP_dATP: cloutier_2009a__dAMP_dATP(dAMP_dATP0, ATP0, ANP, u, Q_adk); AMP: cloutier_2009a__AMP(AMP0, ANP, ATP0, ADP0); ATP_inh: cloutier_2009a__ATP_inh(ATP_inh0, ATP0); AMP_act: cloutier_2009a__AMP_act(AMP_act0, AMP0); v_stim: cloutier_2009a__v_stim(v_stim0, time_); model_parameters: cloutier_2009a__model_parameters(ANP, Q_adk); AMP_pfk2: cloutier_2009a__AMP_pfk2(AMP_pfk20, AMP0); end