/* * A systems biology pipeline for biochemical networks, and its * application to yeast glycolysis * * Model Status * * This CellML model runs in OpenCell and COR to reproduce the * results of the original model. The CellML translation was based * on the original SBML code supplied by the model authors. The * units have been checked and they are consistent. * * Model Structure * * ABSTRACT: * * model diagram * * [[Image file: malys_2010.png]] * * Schematic diagram of the glycolysis pathway described by the * model. * * The original paper reference is cited below: * * A systems biology pipeline for biochemical networks, and its * application to yeast glycolysis, Naglis Malys, Hanan Messiha, * Kathleen Carroll, Warwick Dunn, Farid Khan, Neil W. Hayes, Pinar * Pir, Evangelos Simeonidis, Kieran Smallbone, Irena Spasic, Neil * Swainston, Daniel Jameson, Alice Villeger, Dieter Weichart, * Cate Winder, Jill Wishart, David S. Broomhead, Simon J. Gaskell, * Douglas B. Kell, John E.G. McCarthy, Stephen G. Oliver, Norman * Paton, Hans V. Westerhoff and Pedro Mendes, 2010, */ import nsrunit; unit conversion on; unit mM=1 meter^(-3)*mole^1; unit mM_per_second=1 meter^(-3)*second^(-1)*mole^1; unit mmol_per_second=.001 second^(-1)*mole^1; unit per_mM_per_second=1 meter^3*second^(-1)*mole^(-1); unit per_mM_squared_per_second=1 meter^6*second^(-1)*mole^(-2); unit per_mmol=1E3 mole^(-1); unit per_second=1 second^(-1); unit item=1.6605388 mole^(-24); math main { realDomain time second; time.min=0; extern time.max; extern time.delta; real cell_volume litre; cell_volume=2.155e-14; real Kacald_adh mM; Kacald_adh=1.11; real Kadp_hxk mM; Kadp_hxk=0.23; real Katp_pyk mM; Katp_pyk=1.5; real Kbpg_tdh mM; Kbpg_tdh=0.909; real kcat_adh per_second; kcat_adh=112.3; real Keq_adh dimensionless; Keq_adh=6.9e-5; real Keq_gpm dimensionless; Keq_gpm=0.19; real Keq_hxk dimensionless; Keq_hxk=2000; real Keq_tdh dimensionless; Keq_tdh=0.005334; real Ketoh_adh mM; Ketoh_adh=17; real Kg6p_hxk mM; Kg6p_hxk=30; real Kiacald_adh mM; Kiacald_adh=1.1; real Kietoh_adh mM; Kietoh_adh=90; real Kinad_adh mM; Kinad_adh=0.92; real Kinadh_adh mM; Kinadh_adh=0.031; real Knad_adh mM; Knad_adh=0.17; real Knad_tdh mM; Knad_tdh=0.09; real Knadh_adh mM; Knadh_adh=0.11; real Knadh_tdh mM; Knadh_tdh=0.06; real Kp2g_gpm mM; Kp2g_gpm=0.08; real N_A per_mmol; N_A=6.02214179e20; real percentage_cell_wall dimensionless; percentage_cell_wall=21.8; real percentage_cytoplasm dimensionless; percentage_cytoplasm=47.5; real c_1 litre; c_1=1.023625e-14; real x_01(time) mM; when(time=time.min) x_01=0.329796102; real x_02(time) mM; when(time=time.min) x_02=0.005534; real x_03(time) mM; when(time=time.min) x_03=0.1781; real x_04(time) mM; when(time=time.min) x_04=1.138794213; real x_05(time) mM; when(time=time.min) x_05=0.655861111; real x_06(time) mM; when(time=time.min) x_06=4.394577666; real x_08(time) mM; when(time=time.min) x_08=2.045611826; real x_09(time) mM; when(time=time.min) x_09=0.02; real x_10(time) mM; when(time=time.min) x_10=0.114998749; real x_11(time) mM; when(time=time.min) x_11=2.728563911; real x_12(time) mM; when(time=time.min) x_12=0.484555315; real x_13(time) mM; when(time=time.min) x_13=0.047547092; real x_14(time) mM; when(time=time.min) x_14=1.072770104; real x_15(time) mM; when(time=time.min) x_15=108.3801159; real x_16(time) mM; when(time=time.min) x_16=0.081078255; real x_17(time) mM; when(time=time.min) x_17=36.32137097; real x_18(time) mM; when(time=time.min) x_18=0.133832653; real x_21(time) mM; when(time=time.min) x_21=1.503; real x_22(time) mM; when(time=time.min) x_22=0.08671; real x_23(time) mM; when(time=time.min) x_23=1; real x_24(time) mM; when(time=time.min) x_24=0.223865529; real x_25(time) mM; when(time=time.min) x_25=1.604207403; real x_29(time) mM; when(time=time.min) x_29=0.985981656; real x_30(time) mM; when(time=time.min) x_30=0; real x_31(time) mM; when(time=time.min) x_31=0.050093968; real x_32(time) mM; when(time=time.min) x_32=0.020212786; real x_33(time) mM; when(time=time.min) x_33=0.456977678; real x_36(time) mM; when(time=time.min) x_36=0.535655056; real x_45(time) mM; when(time=time.min) x_45=0.010026905; real x_46(time) mM; when(time=time.min) x_46=0.022824551; real x_47(time) mM; when(time=time.min) x_47=0.014453927; real x_48(time) mM; when(time=time.min) x_48=0.005698838; real x_49(time) mM; when(time=time.min) x_49=2.597164579; real x_50(time) mM; when(time=time.min) x_50=0.027610082; real x_51(time) mM; when(time=time.min) x_51=0.76828054; real x_55(time) mM; when(time=time.min) x_55=1.103267726; real x_57(time) mM; when(time=time.min) x_57=0.111300101; real x_60(time) mM; when(time=time.min) x_60=0.223216643; real x_62(time) mM; when(time=time.min) x_62=0.966352867; real x_63(time) mM; when(time=time.min) x_63=0.537277269; real x_64(time) mM; when(time=time.min) x_64=0.770064975; real x_66(time) mM; when(time=time.min) x_66=0; real x_68(time) mM; when(time=time.min) x_68=0.027610082; real x_69(time) mM; when(time=time.min) x_69=0; real x_72(time) mM; when(time=time.min) x_72=0.079456041; real x_74(time) mM; when(time=time.min) x_74=0.004407555; real x_77(time) mM; when(time=time.min) x_77=0.027610082; real r_01(time) mmol_per_second; real r_02(time) mmol_per_second; real r_03(time) mmol_per_second; real r_04(time) mmol_per_second; real r_05 mmol_per_second; real r_06(time) mmol_per_second; real r_07(time) mmol_per_second; real r_08 mmol_per_second; real r_09(time) mmol_per_second; real r_10(time) mmol_per_second; real r_11(time) mmol_per_second; real r_12(time) mmol_per_second; real r_13(time) mmol_per_second; real r_14(time) mmol_per_second; real r_15(time) mmol_per_second; real r_16(time) mmol_per_second; real r_17(time) mmol_per_second; real r_18(time) mmol_per_second; real r_19(time) mmol_per_second; real r_20(time) mmol_per_second; real r_21(time) mmol_per_second; real r_22(time) mmol_per_second; real r_23(time) mmol_per_second; real r_24(time) mmol_per_second; real r_25(time) mmol_per_second; real r_26(time) mmol_per_second; real r_27(time) mmol_per_second; real r_28 mmol_per_second; real r_29 mmol_per_second; real r_30(time) mmol_per_second; real r_31(time) mmol_per_second; real extracellular.size litre; extracellular.size=1; real x_26(time) mM; when(time=time.min) x_26=51.11; real plasma_membrane.size litre; plasma_membrane.size=4.6979e-15; real r_01.k per_mM_per_second; r_01.k=1.667; real r_01.Keq dimensionless; r_01.Keq=0.45; real Kacald mM; Kacald=0.4622; real r_06.k per_second; r_06.k=0.4011; real r_07.k per_second; r_07.k=0.319; real r_09.kcat per_second; r_09.kcat=26.5; real Kp2g mM; Kp2g=0.066; real r_09.Keq dimensionless; r_09.Keq=6.7; real r_09.Kpep mM; r_09.Kpep=0.5; real r_10.k per_second; r_10.k=0.01384; real r_11.kcat per_second; r_11.kcat=4.139; real r_11.Kf16bp mM; r_11.Kf16bp=0.4507; real r_11.Kdhap mM; r_11.Kdhap=2; real r_11.Kgap mM; r_11.Kgap=2.4; real r_11.Kigap mM; r_11.Kigap=10; real r_11.Keq mM; r_11.Keq=0.069; real r_12.Vmax mM_per_second; r_12.Vmax=3.774; real r_12.Kglc mM; r_12.Kglc=1.192; real Ki dimensionless; Ki=0.91; real r_13.kcat per_second; r_13.kcat=487.4; real Kg6p mM; Kg6p=1.03; real r_13.Kf6p mM; r_13.Kf6p=0.307; real r_13.Keq dimensionless; r_13.Keq=0.29; real r_14.kcat per_second; r_14.kcat=19.12; real r_14.Kgap mM; r_14.Kgap=0.495; real r_15.kcat per_second; r_15.kcat=18.16; real r_15.Kgap mM; r_15.Kgap=0.423; real r_15.Kbpg mM; r_15.Kbpg=0.909; real r_16.kcat per_second; r_16.kcat=15.58; real r_16.Kgap mM; r_16.Kgap=0.21; real r_17.Vmax mM_per_second; r_17.Vmax=13.54; real r_17.Kg3p mM; r_17.Kg3p=3.5; real Kphi mM; Kphi=1; real r_18.Vmax mM_per_second; r_18.Vmax=5.282; real Knadh mM; Knadh=0.023; real r_18.Kdhap mM; r_18.Kdhap=0.54; real Knad mM; Knad=0.93; real r_18.Kg3p mM; r_18.Kg3p=1.2; real r_18.Kf16bp mM; r_18.Kf16bp=4.8; real r_18.Katp mM; r_18.Katp=0.73; real r_18.Kadp mM; r_18.Kadp=2; real r_18.Keq dimensionless; r_18.Keq=10000; real r_19.kcat per_second; r_19.kcat=10.2; real r_19.Kglc mM; r_19.Kglc=0.15; real r_19.Katp mM; r_19.Katp=0.293; real r_20.kcat per_second; r_20.kcat=0.0721; real r_20.Kglc mM; r_20.Kglc=0.0106; real r_20.Katp mM; r_20.Katp=0.865; real r_21.kcat per_second; r_21.kcat=63.1; real r_21.Kglc mM; r_21.Kglc=0.2; real r_21.Katp mM; r_21.Katp=0.195; real r_22.k per_second; r_22.k=3.025; real r_23.kcat per_second; r_23.kcat=117; real gR dimensionless; gR=5.12; real r_23.Kf6p mM; r_23.Kf6p=0.438; real r_23.Katp mM; r_23.Katp=0.008; real L0 dimensionless; L0=0.66; real Ciatp dimensionless; Ciatp=100; real Kiatp mM; Kiatp=0.65; real Camp dimensionless; Camp=0.0845; real Kamp mM; Kamp=0.0995; real Cf26 dimensionless; Cf26=0.0174; real Kf26 mM; Kf26=6.824e-5; real Cf16 dimensionless; Cf16=0.397; real Kf16 mM; Kf16=0.111; real Catp dimensionless; Catp=3; real r_24.kcat per_second; r_24.kcat=58.85; real r_24.Kbpg mM; r_24.Kbpg=0.003; real r_24.Kadp mM; r_24.Kadp=1.99; real r_24.Kp3g mM; r_24.Kp3g=4.58; real r_24.Katp mM; r_24.Katp=3.536; real r_24.Keq dimensionless; r_24.Keq=3200; real nHadp dimensionless; nHadp=2; real r_25.kcat per_second; r_25.kcat=66.61; real r_25.Kp3g mM; r_25.Kp3g=0.681; real r_26.kcat per_second; r_26.kcat=1.776; real r_26.Kpyr mM; r_26.Kpyr=11.44; real r_27.kcat per_second; r_27.kcat=12.07; real r_27.Kpyr mM; r_27.Kpyr=8.331; real r_30.kcat per_second; r_30.kcat=20.13; real r_30.Kpep mM; r_30.Kpep=0.281; real r_30.Kadp mM; r_30.Kadp=0.243; real Keq_pyk dimensionless; Keq_pyk=6500; real Kpyr_pyk mM; Kpyr_pyk=0.6517; real r_31.Keq dimensionless; r_31.Keq=0.0772; real r_31.kcat per_second; r_31.kcat=556.7; real r_31.Kdhap mM; r_31.Kdhap=6.454; real r_31.Kgap mM; r_31.Kgap=5.25; real r_31.Kigap mM; r_31.Kigap=35.1; // // // x_01:time=((r_24-r_25)/c_1); x_02:time=((r_14+r_15+r_16-r_24)/c_1); x_03:time=((r_05+r_26+r_27+r_28-r_02-r_03-r_04)/c_1); x_04:time=((2*r_01+r_06+r_19+r_20+r_21+r_23-r_24-r_29-r_30)/c_1); x_05:time=((-1)*r_01/c_1); x_06:time=((r_24+r_29+r_30-r_01-r_06-r_19-r_20-r_21-r_23)/c_1); x_08:time=((r_23-r_11)/c_1); x_09:time=(0 mM_per_second); x_10:time=((r_13-r_23)/c_1); x_11:time=((r_12-r_19-r_20-r_21)/c_1); x_12:time=((r_19+r_20+r_21-r_13)/c_1); x_13:time=((r_25-r_08-r_09)/c_1); x_14:time=((r_11-r_18-r_31)/c_1); x_15:time=((r_02+r_03+r_04-r_05-r_10)/c_1); x_16:time=((r_11+r_31-r_14-r_15-r_16)/c_1); x_17:time=(0 mM_per_second); x_18:time=((r_18-r_17)/c_1); x_21:time=((r_02+r_03+r_04+r_18+r_22-r_05-r_14-r_15-r_16)/c_1); x_22:time=((r_05+r_14+r_15+r_16-r_02-r_03-r_04-r_18-r_22)/c_1); x_23:time=(0 mM_per_second); x_24:time=((r_08+r_09-r_29-r_30)/c_1); x_25:time=((r_29+r_30-r_07-r_26-r_27-r_28)/c_1); x_29:time=(0 mM_per_second); x_30:time=(0 mM_per_second); x_31:time=(0 mM_per_second); x_32:time=(0 mM_per_second); x_33:time=(0 mM_per_second); x_36:time=(0 mM_per_second); x_45:time=(0 mM_per_second); x_46:time=(0 mM_per_second); x_47:time=(0 mM_per_second); x_48:time=(0 mM_per_second); x_49:time=(0 mM_per_second); x_50:time=(0 mM_per_second); x_51:time=(0 mM_per_second); x_55:time=(0 mM_per_second); x_57:time=(0 mM_per_second); x_60:time=(0 mM_per_second); x_62:time=(0 mM_per_second); x_63:time=(0 mM_per_second); x_64:time=(0 mM_per_second); x_66:time=(0 mM_per_second); x_68:time=(0 mM_per_second); x_69:time=(0 mM_per_second); x_72:time=(0 mM_per_second); x_74:time=(0 mM_per_second); x_77:time=(0 mM_per_second); // x_26:time=(0 mM_per_second); // // r_01=(c_1*r_01.k*(x_06*x_05-x_04*x_04/r_01.Keq)); // r_02=(c_1*((-1)*x_47)*kcat_adh*(x_15*x_21/(Ketoh_adh*Kinad_adh)-x_03*x_22/(Ketoh_adh*Kinad_adh*Keq_adh))/(1+x_21/Kinad_adh+x_15*Knad_adh/(Kinad_adh*Ketoh_adh)+x_03*Knadh_adh/(Kinadh_adh*Kacald_adh)+x_22/Kinadh_adh+x_15*x_21/(Kinad_adh*Ketoh_adh)+x_21*x_03*Knadh_adh/(Kinad_adh*Kinadh_adh*Kacald_adh)+x_15*x_22*Knad_adh/(Kinad_adh*Kinadh_adh*Ketoh_adh)+x_03*x_22/(Kacald_adh*Kinadh_adh)+x_15*x_21*x_03/(Kinad_adh*Kiacald_adh*Ketoh_adh)+x_15*x_03*x_22/(Kietoh_adh*Kinadh_adh*Kacald_adh))); // r_03=(c_1*((-1)*x_30)*kcat_adh*(x_15*x_21/(Ketoh_adh*Kinad_adh)-x_03*x_22/(Ketoh_adh*Kinad_adh*Keq_adh))/(1+x_21/Kinad_adh+x_15*Knad_adh/(Kinad_adh*Ketoh_adh)+x_03*Knadh_adh/(Kinadh_adh*Kacald_adh)+x_22/Kinadh_adh+x_15*x_21/(Kinad_adh*Ketoh_adh)+x_21*x_03*Knadh_adh/(Kinad_adh*Kinadh_adh*Kacald_adh)+x_15*x_22*Knad_adh/(Kinad_adh*Kinadh_adh*Ketoh_adh)+x_03*x_22/(Kacald_adh*Kinadh_adh)+x_15*x_21*x_03/(Kinad_adh*Kiacald_adh*Ketoh_adh)+x_15*x_03*x_22/(Kietoh_adh*Kinadh_adh*Kacald_adh))); // r_04=(c_1*((-1)*x_72)*kcat_adh*(x_15*x_21/(Ketoh_adh*Kinad_adh)-x_03*x_22/(Ketoh_adh*Kinad_adh*Keq_adh))/(1+x_21/Kinad_adh+x_15*Knad_adh/(Kinad_adh*Ketoh_adh)+x_03*Knadh_adh/(Kinadh_adh*Kacald)+x_22/Kinadh_adh+x_15*x_21/(Kinad_adh*Ketoh_adh)+x_21*x_03*Knadh_adh/(Kinad_adh*Kinadh_adh*Kacald)+x_15*x_22*Knad_adh/(Kinad_adh*Kinadh_adh*Ketoh_adh)+x_03*x_22/(Kacald*Kinadh_adh)+x_15*x_21*x_03/(Kinad_adh*Kiacald_adh*Ketoh_adh)+x_15*x_03*x_22/(Kietoh_adh*Kinadh_adh*Kacald))); // r_05=(0 mmol_per_second); // r_06=(c_1*r_06.k*x_06); // r_07=(c_1*r_07.k*x_25); // r_08=(0 mmol_per_second); // r_09=(c_1*x_51*r_09.kcat*(x_13/Kp2g-x_24/(Kp2g*r_09.Keq))/(1+x_13/Kp2g+x_24/r_09.Kpep)); // r_10=(c_1*r_10.k*x_15); // r_11=(c_1*x_62*r_11.kcat*(x_08/r_11.Kf16bp-x_14*x_16/(r_11.Kf16bp*r_11.Keq))/(1+x_08/r_11.Kf16bp+x_14/r_11.Kdhap+x_16/r_11.Kgap+x_08*x_16/(r_11.Kf16bp*r_11.Kigap)+x_14*x_16/(r_11.Kdhap*r_11.Kgap))); // r_12=(c_1*r_12.Vmax*(x_26-x_11)/r_12.Kglc/(1+x_26/r_12.Kglc+x_11/r_12.Kglc+Ki*x_26/r_12.Kglc*x_11/r_12.Kglc)); // r_13=(c_1*x_31*r_13.kcat*(x_12/Kg6p-x_10/(Kg6p*r_13.Keq))/(1+x_12/Kg6p+x_10/r_13.Kf6p)); // r_14=(c_1*x_57*r_14.kcat*(x_16*x_21/(r_14.Kgap*Knad_tdh)-x_02*x_22/(r_14.Kgap*Knad_tdh*Keq_tdh))/((1+x_16/r_14.Kgap+x_02/Kbpg_tdh)*(1+x_21/Knad_tdh+x_22/Knadh_tdh))); // r_15=(c_1*x_49*r_15.kcat*(x_16*x_21/(r_15.Kgap*Knad_tdh)-x_02*x_22/(r_15.Kgap*Knad_tdh*Keq_tdh))/((1+x_16/r_15.Kgap+x_02/r_15.Kbpg)*(1+x_21/Knad_tdh+x_22/Knadh_tdh))); // r_16=(c_1*x_60*r_16.kcat*(x_16*x_21/(r_16.Kgap*Knad_tdh)-x_02*x_22/(r_16.Kgap*Knad_tdh*Keq_tdh))/((1+x_16/r_16.Kgap+x_02/Kbpg_tdh)*(1+x_21/Knad_tdh+x_22/Knadh_tdh))); // r_17=(c_1*r_17.Vmax*x_18/r_17.Kg3p/((1+x_18/r_17.Kg3p)*(1+x_23/Kphi))); // r_18=(c_1*r_18.Vmax/(Knadh*r_18.Kdhap)*(x_22*x_14-x_21*x_18/r_18.Keq)/((1+x_08/r_18.Kf16bp+x_06/r_18.Katp+x_04/r_18.Kadp)*(1+x_22/Knadh+x_21/Knad)*(1+x_14/r_18.Kdhap+x_18/r_18.Kg3p))); // r_19=(c_1*x_45*r_19.kcat*(x_11*x_06/(r_19.Kglc*r_19.Katp)-x_12*x_04/(r_19.Kglc*r_19.Katp*Keq_hxk))/((1+x_11/r_19.Kglc+x_12/Kg6p_hxk)*(1+x_06/r_19.Katp+x_04/Kadp_hxk))); // r_20=(c_1*x_32*r_20.kcat*(x_11*x_06/(r_20.Kglc*r_20.Katp)-x_12*x_04/(r_20.Kglc*r_20.Katp*Keq_hxk))/((1+x_11/r_20.Kglc+x_12/Kg6p_hxk)*(1+x_06/r_20.Katp+x_04/Kadp_hxk))); // r_21=(c_1*x_46*r_21.kcat*(x_11*x_06/(r_21.Kglc*r_21.Katp)-x_12*x_04/(r_21.Kglc*r_21.Katp*Keq_hxk))/((1+x_11/r_21.Kglc+x_12/Kg6p_hxk)*(1+x_06/r_21.Katp+x_04/Kadp_hxk))); // r_22=(c_1*r_22.k*x_22); // r_23=(c_1*x_77*r_23.kcat*gR*x_10/r_23.Kf6p*x_06/r_23.Katp*(1+x_10/r_23.Kf6p+x_06/r_23.Katp+gR*x_10/r_23.Kf6p*x_06/r_23.Katp)/((1+x_10/r_23.Kf6p+x_06/r_23.Katp+gR*x_10/r_23.Kf6p*x_06/r_23.Katp)^2+L0*((1+Ciatp*x_06/Kiatp)/(1+x_06/Kiatp))^2*((1+Camp*x_05/Kamp)/(1+x_05/Kamp))^2*((1+Cf26*x_09/Kf26+Cf16*x_08/Kf16)/(1+x_09/Kf26+x_08/Kf16))^2*(1+Catp*x_06/r_23.Katp)^2)); // r_24=(c_1*x_33*r_24.kcat*(x_04/r_24.Kadp)^(nHadp-1)*(x_02*x_04/(r_24.Kbpg*r_24.Kadp)-x_01*x_06/(r_24.Kbpg*r_24.Kadp*r_24.Keq))/((1+x_02/r_24.Kbpg+x_01/r_24.Kp3g)*(1+(x_04/r_24.Kadp)^nHadp+x_06/r_24.Katp))); // r_25=(c_1*x_63*r_25.kcat*(x_01/r_25.Kp3g-x_13/(r_25.Kp3g*Keq_gpm))/(1+x_01/r_25.Kp3g+x_13/Kp2g_gpm)); // r_26=(c_1*x_66*r_26.kcat*x_25/r_26.Kpyr/(1+x_25/r_26.Kpyr)); // r_27=(c_1*x_64*r_27.kcat*x_25/r_27.Kpyr/(1+x_25/r_27.Kpyr)); // r_28=(0 mmol_per_second); // r_29=(0 mmol_per_second); // r_30=(c_1*x_29*r_30.kcat*(x_24*x_04/(r_30.Kpep*r_30.Kadp)-x_25*x_06/(r_30.Kpep*r_30.Kadp*Keq_pyk))/((1+x_24/r_30.Kpep+x_25/Kpyr_pyk)*(1+x_04/r_30.Kadp+x_06/Katp_pyk))); // r_31=(c_1*x_36*r_31.kcat/r_31.Kdhap*(x_14-x_16/r_31.Keq)/(1+x_14/r_31.Kdhap+x_16/r_31.Kgap*(1+(x_16/r_31.Kigap)^4))); }