(* Generated by JWS Online *) (* This is an experimental feature of JWS Online. Please report any mistakes.*) (* Note that the following notable SBML entities or features are not supported in notebook outputyet: *) (* Events *) (* Constraints *) (* Units and UnitDefinitions *) (* AlgebraicRules *) (* conversionFactors *) variables = { ADP[t], AMP[t], ATP[t], DHAP[t], F6P[t], FBP[t], G3P[t], G6P[t], Gluin[t], Lacin[t], NAD[t], NADH[t], PEP[t], Pyr[t], \[LetterSpace]13BPG[t], \[LetterSpace]2PG[t], \[LetterSpace]3PG[t] }; initialValues = { ADP[0] == 2.4, AMP[0] == 1.1, ATP[0] == 9.0, DHAP[0] == 0.5, F6P[0] == 2.0, FBP[0] == 0.6, G3P[0] == 0.27, G6P[0] == 2.6, Gluin[0] == 0.001, Lacin[0] == 33.0, NAD[0] == 1.3, NADH[0] == 0.05, PEP[0] == 0.35, Pyr[0] == 3.0, \[LetterSpace]13BPG[0] == 0.001, \[LetterSpace]2PG[0] == 0.001, \[LetterSpace]3PG[0] == 0.001 }; rates = { AK, ALDO, ATPases, DHases, ENO, GAPDH, GLUT, Glycogen\[LetterSpace]degradation, Glycogen\[LetterSpace]synthesis, HK, HPI, LDH, MCT1, MPM, OxPhos, PFK1, PGAM, PGK, PPP, PYK, TK, TPI }; rateEquations = { AK -> compartment*(-(AK\[LetterSpace]k2*ADP[t]^2) + AK\[LetterSpace]k1*AMP[t]*ATP[t]), ALDO -> compartment*ALDO\[LetterSpace]rate\[LetterSpace]equation[FBP[t], DHAP[t], G3P[t], ALDO\[LetterSpace]Vmf, ALDO\[LetterSpace]Kfbp, ALDO\[LetterSpace]Vmr, ALDO\[LetterSpace]Kdhap, ALDO\[LetterSpace]Kg3p], ATPases -> ATPases\[LetterSpace]k1*compartment*ATP[t], DHases -> compartment*(-(DHases\[LetterSpace]k2*NAD[t]) + DHases\[LetterSpace]k1*NADH[t]), ENO -> compartment*Reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[\[LetterSpace]2PG[t], PEP[t], ENO\[LetterSpace]Kms, ENO\[LetterSpace]Kmp, ENO\[LetterSpace]Vf, ENO\[LetterSpace]Vr], GAPDH -> compartment*GAPDH\[LetterSpace]0[NAD[t], G3P[t], Pi, \[LetterSpace]13BPG[t], NADH[t], GAPDH\[LetterSpace]Vmf, GAPDH\[LetterSpace]Knad, GAPDH\[LetterSpace]Kg3p, GAPDH\[LetterSpace]Kp, GAPDH\[LetterSpace]Vmr, GAPDH\[LetterSpace]Kdpg, GAPDH\[LetterSpace]Knadh], GLUT -> compartment*GLUT\[LetterSpace]isoforms\[LetterSpace]rate\[LetterSpace]equation[Gluout, Gluin[t], GLUT\[LetterSpace]Vmf, GLUT\[LetterSpace]f1, GLUT\[LetterSpace]Keq, GLUT\[LetterSpace]Kgluout, GLUT\[LetterSpace]Kgluin, GLUT\[LetterSpace]f2, GLUT\[LetterSpace]Keq1, GLUT\[LetterSpace]Kgluout1, GLUT\[LetterSpace]Kgluin1], Glycogen\[LetterSpace]degradation -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[Glycogen\[LetterSpace]degradation\[LetterSpace]v], Glycogen\[LetterSpace]synthesis -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[Glycogen\[LetterSpace]synthesis\[LetterSpace]v], HK -> compartment*HK\[LetterSpace]isoforms\[LetterSpace]rate\[LetterSpace]equation[Gluin[t], ATP[t], G6P[t], ADP[t], HK\[LetterSpace]Vm, HK\[LetterSpace]f1, HK\[LetterSpace]Ka, HK\[LetterSpace]Kb, HK\[LetterSpace]Keq, HK\[LetterSpace]Kp, HK\[LetterSpace]Kq, HK\[LetterSpace]f2, HK\[LetterSpace]Ka2], HPI -> compartment*HPI\[LetterSpace]rate\[LetterSpace]equation[G6P[t], F6P[t], Ery4P, FBP[t], \[LetterSpace]6PG, HPI\[LetterSpace]Vmf, HPI\[LetterSpace]Kg6p, HPI\[LetterSpace]Vmr, HPI\[LetterSpace]Kf6p, HPI\[LetterSpace]Kery4p, HPI\[LetterSpace]Kfbp, HPI\[LetterSpace]Kpg], LDH -> compartment*Random\[LetterSpace]Bi\[LetterSpace]Bi\[LetterSpace]reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[NADH[t], Pyr[t], Lacin[t], NAD[t], LDH\[LetterSpace]Vmf, LDH\[LetterSpace]alfa, LDH\[LetterSpace]Ka, LDH\[LetterSpace]Kb, LDH\[LetterSpace]Vmr, LDH\[LetterSpace]beta, LDH\[LetterSpace]Kp, LDH\[LetterSpace]Kq], MCT1 -> compartment*MCT1\[LetterSpace]0[Lacin[t], Lacout, MCT1\[LetterSpace]Vmf, MCT1\[LetterSpace]Keq, MCT1\[LetterSpace]Klacin, MCT1\[LetterSpace]Klacout], MPM -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[MPM\[LetterSpace]v], OxPhos -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[OxPhos\[LetterSpace]v], PFK1 -> compartment*PFK\[LetterSpace]1\[LetterSpace]rate\[LetterSpace]equation[F6P[t], ATP[t], FBP[t], ADP[t], F26BP, Cit, PFK1\[LetterSpace]Vm, PFK1\[LetterSpace]Katp, PFK1\[LetterSpace]beta, PFK1\[LetterSpace]alfa, PFK1\[LetterSpace]Kf26bp, PFK1\[LetterSpace]Kf6p, PFK1\[LetterSpace]L, PFK1\[LetterSpace]Kcit, PFK1\[LetterSpace]Kiatp, PFK1\[LetterSpace]Kadp, PFK1\[LetterSpace]Kfbp, PFK1\[LetterSpace]Keq], PGAM -> compartment*Reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[\[LetterSpace]3PG[t], \[LetterSpace]2PG[t], PGAM\[LetterSpace]Kms, PGAM\[LetterSpace]Kmp, PGAM\[LetterSpace]Vf, PGAM\[LetterSpace]Vr], PGK -> compartment*Random\[LetterSpace]Bi\[LetterSpace]Bi\[LetterSpace]reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[\[LetterSpace]13BPG[t], ADP[t], \[LetterSpace]3PG[t], ATP[t], PGK\[LetterSpace]Vmf, PGK\[LetterSpace]alfa, PGK\[LetterSpace]Ka, PGK\[LetterSpace]Kb, PGK\[LetterSpace]Vmr, PGK\[LetterSpace]beta, PGK\[LetterSpace]Kp, PGK\[LetterSpace]Kq], PPP -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[PPP\[LetterSpace]v], PYK -> compartment*PYK\[LetterSpace]kinetics[PEP[t], ADP[t], Pyr[t], ATP[t], PYK\[LetterSpace]Vmax, PYK\[LetterSpace]Kpep, PYK\[LetterSpace]Kadp, PYK\[LetterSpace]Keq, PYK\[LetterSpace]Kpyr, PYK\[LetterSpace]Katp], TK -> compartment*Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[TK\[LetterSpace]v], TPI -> compartment*Reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[DHAP[t], G3P[t], TPI\[LetterSpace]Kms, TPI\[LetterSpace]Kmp, TPI\[LetterSpace]Vf, TPI\[LetterSpace]Vr] }; parameters = { Cit -> 1.7, Ery4P -> 0.23, F26BP -> 0.0033, Gluout -> 5.0, Lacout -> 1.2, Pi -> 4.0, Xy5P -> 0.016, \[LetterSpace]6PG -> 0.48, glycogen -> 17.4, GLUT\[LetterSpace]Vmf -> 0.028, GLUT\[LetterSpace]f1 -> 0.1, GLUT\[LetterSpace]Keq -> 1.0, GLUT\[LetterSpace]Kgluout -> 1.8, GLUT\[LetterSpace]Kgluin -> 10.0, GLUT\[LetterSpace]f2 -> 0.9, GLUT\[LetterSpace]Keq1 -> 1.0, GLUT\[LetterSpace]Kgluout1 -> 9.3, GLUT\[LetterSpace]Kgluin1 -> 10.0, HK\[LetterSpace]Vm -> 0.041, HK\[LetterSpace]f1 -> 0.01, HK\[LetterSpace]Ka -> 0.03, HK\[LetterSpace]Kb -> 1.1, HK\[LetterSpace]Keq -> 651.0, HK\[LetterSpace]Kp -> 0.02, HK\[LetterSpace]Kq -> 3.5, HK\[LetterSpace]f2 -> 0.99, HK\[LetterSpace]Ka2 -> 0.3, HPI\[LetterSpace]Vmf -> 0.28, HPI\[LetterSpace]Kg6p -> 0.4, HPI\[LetterSpace]Vmr -> 0.63, HPI\[LetterSpace]Kf6p -> 0.05, HPI\[LetterSpace]Kery4p -> 0.001, HPI\[LetterSpace]Kfbp -> 0.06, HPI\[LetterSpace]Kpg -> 0.015, PFK1\[LetterSpace]Vm -> 0.022, PFK1\[LetterSpace]Katp -> 0.0292, PFK1\[LetterSpace]beta -> 1.18, PFK1\[LetterSpace]alfa -> 0.75, PFK1\[LetterSpace]Kf26bp -> 0.00099, PFK1\[LetterSpace]Kf6p -> 1.1, PFK1\[LetterSpace]L -> 6.6, PFK1\[LetterSpace]Kcit -> 6.7, PFK1\[LetterSpace]Kiatp -> 1.1, PFK1\[LetterSpace]Kadp -> 5.0, PFK1\[LetterSpace]Kfbp -> 5.0, PFK1\[LetterSpace]Keq -> 247.0, ALDO\[LetterSpace]Vmf -> 0.08, ALDO\[LetterSpace]Kfbp -> 0.009, ALDO\[LetterSpace]Vmr -> 0.063, ALDO\[LetterSpace]Kdhap -> 0.08, ALDO\[LetterSpace]Kg3p -> 0.16, TPI\[LetterSpace]Kms -> 1.6, TPI\[LetterSpace]Kmp -> 0.51, TPI\[LetterSpace]Vf -> 3.4, TPI\[LetterSpace]Vr -> 28.0, GAPDH\[LetterSpace]Vmf -> 0.331, GAPDH\[LetterSpace]Knad -> 0.09, GAPDH\[LetterSpace]Kg3p -> 0.19, GAPDH\[LetterSpace]Kp -> 11.0, GAPDH\[LetterSpace]Vmr -> 0.413, GAPDH\[LetterSpace]Kdpg -> 0.022, GAPDH\[LetterSpace]Knadh -> 0.01, PGK\[LetterSpace]Vmf -> 8.7, PGK\[LetterSpace]alfa -> 1.0, PGK\[LetterSpace]Ka -> 0.079, PGK\[LetterSpace]Kb -> 0.04, PGK\[LetterSpace]Vmr -> 2.5, PGK\[LetterSpace]beta -> 1.0, PGK\[LetterSpace]Kp -> 0.13, PGK\[LetterSpace]Kq -> 0.27, PGAM\[LetterSpace]Kms -> 0.19, PGAM\[LetterSpace]Kmp -> 0.12, PGAM\[LetterSpace]Vf -> 0.94, PGAM\[LetterSpace]Vr -> 0.36, ENO\[LetterSpace]Kms -> 0.038, ENO\[LetterSpace]Kmp -> 0.06, ENO\[LetterSpace]Vf -> 0.34, ENO\[LetterSpace]Vr -> 0.38, PYK\[LetterSpace]Vmax -> 0.087, PYK\[LetterSpace]Kpep -> 0.05, PYK\[LetterSpace]Kadp -> 0.4, PYK\[LetterSpace]Keq -> 195172.4, PYK\[LetterSpace]Kpyr -> 10.0, PYK\[LetterSpace]Katp -> 0.86, LDH\[LetterSpace]Vmf -> 0.468, LDH\[LetterSpace]alfa -> 1.0, LDH\[LetterSpace]Ka -> 0.002, LDH\[LetterSpace]Kb -> 0.3, LDH\[LetterSpace]Vmr -> 0.074, LDH\[LetterSpace]beta -> 1.0, LDH\[LetterSpace]Kp -> 4.7, LDH\[LetterSpace]Kq -> 0.07, Glycogen\[LetterSpace]degradation\[LetterSpace]v -> 0.0045, ATPases\[LetterSpace]k1 -> 0.00322, AK\[LetterSpace]k1 -> 1.0, AK\[LetterSpace]k2 -> 2.26, DHases\[LetterSpace]k1 -> 250.0, DHases\[LetterSpace]k2 -> 1.0, PPP\[LetterSpace]v -> 9.5*^-05, Glycogen\[LetterSpace]synthesis\[LetterSpace]v -> 0.001, MPM\[LetterSpace]v -> 0.0001, TK\[LetterSpace]v -> 9.5*^-05, MCT1\[LetterSpace]Vmf -> 0.03, MCT1\[LetterSpace]Keq -> 1.0, MCT1\[LetterSpace]Klacin -> 8.5, MCT1\[LetterSpace]Klacout -> 0.5, OxPhos\[LetterSpace]v -> 0.01875, compartment -> 1.0 }; assignments = { MCT1\[LetterSpace]0[Lacin_,Lacout_,Vmf_,Keq_,Klacin_,Klacout_] -> ((Lacin - Lacout/Keq)*Vmf)/(Lacin + Klacin*(1 + Lacout/Klacout)), GLUT\[LetterSpace]isoforms\[LetterSpace]rate\[LetterSpace]equation[Gluout_,Gluin_,Vmf_,f1_,Keq_,Kgluout_,Kgluin_,f2_,Keq1_,Kgluout1_,Kgluin1_] -> ((f1*(Gluout - Gluin/Keq))/(Gluout + (1 + Gluin/Kgluin)*Kgluout) + (f2*(Gluout - Gluin/Keq1))/(Gluout + (1 + Gluin/Kgluin1)*Kgluout1))*Vmf, Random\[LetterSpace]Bi\[LetterSpace]Bi\[LetterSpace]reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[A_,B_,P_,Q_,Vmf_,alfa_,Ka_,Kb_,Vmr_,beta_,Kp_,Kq_] -> ((A*B*Vmf)/(alfa*Ka*Kb) - (P*Q*Vmr)/(beta*Kp*Kq))/(1 + A/Ka + B/Kb + (A*B)/(alfa*Ka*Kb) + P/Kp + Q/Kq + (P*Q)/(beta*Kp*Kq)), Constant\[LetterSpace]flux\[LetterSpace]\[LetterSpace]irreversible[v_] -> v, Reversible\[LetterSpace]Michaelis\[LetterSpace]Menten[substrate_,product_,Kms_,Kmp_,Vf_,Vr_] -> ((substrate*Vf)/Kms - (product*Vr)/Kmp)/(1 + product/Kmp + substrate/Kms), PYK\[LetterSpace]kinetics[A_,B_,P_,Q_,Vmax_,Kpep_,Kadp_,Keq_,Kpyr_,Katp_] -> (((A*B)/(Kadp*Kpep) - (P*Q)/(Kadp*Keq*Kpep))*Vmax)/((1 + A/Kpep + P/Kpyr)*(1 + B/Kadp + Q/Katp)), HPI\[LetterSpace]rate\[LetterSpace]equation[G6P_,F6P_,ERY4P_,FBP_,PG_,Vmf_,Kg6p_,Vmr_,Kf6p_,Kery4p_,Kfbp_,Kpg_] -> ((G6P*Vmf)/Kg6p - (F6P*Vmr)/Kf6p)/(1 + ERY4P/Kery4p + F6P/Kf6p + FBP/Kfbp + G6P/Kg6p + PG/Kpg), GAPDH\[LetterSpace]0[NAD_,G3P_,P_,DPG_,NADH_,Vmf_,Knad_,Kg3p_,Kp_,Vmr_,Kdpg_,Knadh_] -> ((G3P*NAD*P*Vmf)/(Kg3p*Knad*Kp) - (DPG*NADH*Vmr)/(Kdpg*Knadh))/(1 + NAD/Knad + (G3P*NAD)/(Kg3p*Knad) + NADH/Knadh + (DPG*NADH)/(Kdpg*Knadh) + (G3P*NAD*P)/(Kg3p*Knad*Kp)), PFK\[LetterSpace]1\[LetterSpace]rate\[LetterSpace]equation[ATP_,F6P_,ADP_,FBP_,F26BP_,CIT_,Vm_,Katp_,beta_,alfa_,Kf26bp_,Kf6p_,L_,Kcit_,Kiatp_,Kadp_,Kfbp_,Keq_] -> (ATP*(1 + (beta*F26BP)/(alfa*Kf26bp))*(-((ADP*FBP)/(Kadp*Keq*(1 + ADP/Kadp + FBP/Kfbp + (ADP*FBP)/(Kadp*Kfbp))*Kfbp)) + (F6P*(1 + F26BP/(alfa*Kf26bp))*(1 + (F6P*(1 + F26BP/(alfa*Kf26bp)))/((1 + F26BP/Kf26bp)*Kf6p))^3)/((1 + F26BP/Kf26bp)*Kf6p*((1 + (F6P*(1 + F26BP/(alfa*Kf26bp)))/((1 + F26BP/Kf26bp)*Kf6p))^4 + ((1 + CIT/Kcit)^4*(1 + ATP/Kiatp)^4*L)/(1 + F26BP/Kf26bp)^4)))*Vm)/((1 + ATP/Katp)*Katp*(1 + F26BP/(alfa*Kf26bp))), ALDO\[LetterSpace]rate\[LetterSpace]equation[FBP_,DHAP_,G3P_,Vmf_,Kfbp_,Vmr_,Kdhap_,Kg3p_] -> ((FBP*Vmf)/Kfbp - (DHAP*G3P*Vmr)/(Kdhap*Kg3p))/(1 + DHAP/Kdhap + FBP/Kfbp + G3P/Kg3p + (DHAP*G3P)/(Kdhap*Kg3p)), HK\[LetterSpace]isoforms\[LetterSpace]rate\[LetterSpace]equation[A_,B_,P_,Q_,Vm_,f1_,Ka_,Kb_,Keq_,Kp_,Kq_,f2_,Ka2_] -> ((f1*(A*B - (P*Q)/Keq))/(Ka*Kb*(1 + A/Ka + B/Kb + (A*B)/(Ka*Kb) + P/Kp + (B*P)/(Kb*Kp) + Q/Kq + (A*Q)/(Ka*Kq) + (P*Q)/(Kp*Kq))) + (f2*(A*B - (P*Q)/Keq))/(Ka2*Kb*(1 + A/Ka2 + B/Kb + (A*B)/(Ka2*Kb) + P/Kp + (B*P)/(Kb*Kp) + Q/Kq + (A*Q)/(Ka2*Kq) + (P*Q)/(Kp*Kq))))*Vm }; events = { }; speciesAnnotations = { }; reactionAnnotations = { }; units = { {"time" -> "", "metabolite" -> "", "extent" -> ""} }; (* Time evolution *) odes = { ADP'[t] == 1.0*HK +1.0*PFK1 +1.0*ATPases +2.0*AK +1.0*Glycogen\[LetterSpace]synthesis -1.0*PGK -1.0*PYK -13.0*MPM -1.0*OxPhos, AMP'[t] == -1.0*AK, ATP'[t] == 1.0*PGK +1.0*PYK +13.0*MPM +1.0*OxPhos -1.0*HK -1.0*PFK1 -1.0*ATPases -1.0*AK -1.0*Glycogen\[LetterSpace]synthesis, DHAP'[t] == 1.0*ALDO -1.0*TPI, F6P'[t] == 1.0*HPI +1.0*TK -1.0*PFK1, FBP'[t] == 1.0*PFK1 -1.0*ALDO, G3P'[t] == 1.0*ALDO +1.0*TPI +1.0*TK -1.0*GAPDH, G6P'[t] == 1.0*HK +1.0*Glycogen\[LetterSpace]degradation -1.0*HPI -1.0*PPP -1.0*Glycogen\[LetterSpace]synthesis, Gluin'[t] == 1.0*GLUT -1.0*HK, Lacin'[t] == 1.0*LDH -1.0*MCT1, NAD'[t] == 1.0*LDH +1.0*DHases -1.0*GAPDH, NADH'[t] == 1.0*GAPDH -1.0*LDH -1.0*DHases, PEP'[t] == 1.0*ENO -1.0*PYK, Pyr'[t] == 1.0*PYK -1.0*LDH -1.0*MPM, \[LetterSpace]13BPG'[t] == 1.0*GAPDH -1.0*PGK, \[LetterSpace]2PG'[t] == 1.0*PGAM -1.0*ENO, \[LetterSpace]3PG'[t] == 1.0*PGK -1.0*PGAM }; timeCourse = NDSolve[Join[odes, initialValues]//.rateEquations//.assignments//.parameters, variables, {t, 0, 100}]; (* Steady-state solution initialized with result of time evolution *) findRootEquations = odes /.D[_[t],t]->0; findRootVariables = Partition[Flatten[{#, #/.timeCourse/.t->100} &/@variables],2]; steadyStateVariables = FindRoot[findRootEquations//.rateEquations//.assignments//.parameters, findRootVariables, MaxIterations->100] fluxes = #//.assignments//.parameters/.steadyStateVariables&/@rateEquations (* Plot the time evolution of the variables *) plotTable=Table[Plot[variables[[i]]/.parameters/.timeCourse,{t,0,100},PlotLegends->variables[[i]],PlotRange->Full],{i,Length[variables]}]