// Created by libAntimony v2.8.0 function function_4_b_glu_loss_1(b_glu) 0.1*b_glu; end function function_1(v) v; end function function_4_VmHCOOHc_1(c_coo, cytosol, k_in_coo, k_out_coo, m_coo, mito) (k_in_coo*m_coo*mito)/3 - k_out_coo*c_coo*cytosol; end function function_4_b_cys_cystine_conv_1(b_cys) 0.25*b_cys; end function function_4_b_gsg_decomp_1(b_gsg) 67.5*b_gsg; end function function_4_b_cys_loss_1(b_cys) 0.1*b_cys; end function function_4_b_gsh_decomp_1(b_gsh) 90*b_gsh; end function function_4_V_GDC_1(K_gly_GDC, K_thf_GDC, Vm_GDC, m_gly, m_thf) (Vm_GDC*m_thf*m_gly)/((K_thf_GDC + m_thf)*(K_gly_GDC + m_gly)); end function function_4_b_gsg_loss_1(b_gsg) 7.5*b_gsg; end function function_4_VmNE_1(HCHO, k1_mNE, k2_mNE, m_2cf, m_thf, mito) mito*(k1_mNE*m_thf*HCHO - k2_mNE*m_2cf); end function function_4_b_gsh_loss_1(b_gsh) 0.7*b_gsh; end function function_4_b_gly_loss_1(b_gly) 0.1*b_gly; end function function_4_VmFTD_1(K_10f_FTD, Vm_mFTD, m_10f) (Vm_mFTD*m_10f)/(K_10f_FTD + m_10f); end function MM_twosubst(Vmax, Km1, Km2, S1, S2) (Vmax*S1*S2)/((Km1 + S1)*(Km2 + S2)); end function MM(Vmax, Km, S) (Vmax*S)/(Km + S); end function function_4_V_c_gshLb_1(K_gshLb, V_gshLb, c_gsh, cytosol, h_gshLb) (cytosol*V_gshLb*c_gsh^h_gshLb)/(K_gshLb^h_gshLb + c_gsh^h_gshLb); end function function_4_V_MS_1(H2O2, K_5mf_MS, K_hcy_MS, Ki_MS, Vm_MS, c_5mf, hcy, ssH2O2) (MM_twosubst(Vm_MS, K_5mf_MS, K_hcy_MS, c_5mf, hcy)*(ssH2O2 + Ki_MS))/(H2O2 + Ki_MS); end function function_4_V_DHFR_1(K_NADPH_DHFR, K_dhf_DHFR, NADPH, Vm_DHFR, c_dhf) (Vm_DHFR*c_dhf*NADPH)/((K_dhf_DHFR + c_dhf)*(K_NADPH_DHFR + NADPH)); end function function_4_VcFTD_1(K_10f_FTD, Vm_cFTD, c_10f) (Vm_cFTD*c_10f)/(K_10f_FTD + c_10f); end function function_4_V_PGT_1(GAR, K_10f_PGT, K_GAR_PGT, Vm_PGT, c_10f) (Vm_PGT*c_10f*GAR)/((K_10f_PGT + c_10f)*(K_GAR_PGT + GAR)); end function function_4_VcFTS_1(K_coo_cFTS, K_thf_cFTS, Vm_cFTS, c_coo, c_thf) (Vm_cFTS*c_thf*c_coo)/((K_thf_cFTS + c_thf)*(K_coo_cFTS + c_coo)); end function function_4_VcSHMT_1(K_2cf_SHMT, K_gly_SHMT, K_ser_SHMT, K_thf_SHMT, Vf_cSHMT, Vr_cSHMT, c_2cf, c_gly, c_ser, c_thf) MM_twosubst(Vf_cSHMT, K_thf_SHMT, K_ser_SHMT, c_thf, c_ser) - MM_twosubst(Vr_cSHMT, K_gly_SHMT, K_2cf_SHMT, c_gly, c_2cf); end function function_4_VcNE_1(HCHO, c_2cf, c_thf, cytosol, k1_cNE, k2_cNE) cytosol*(k1_cNE*c_thf*HCHO - k2_cNE*c_2cf); end function function_4_V_TS_1(DUMP, K_2cf_TS, K_DUMP_TS, Vm_TS, c_2cf) (Vm_TS*DUMP*c_2cf)/((K_DUMP_TS + DUMP)*(K_2cf_TS + c_2cf)); end function function_4_V_MTHFR_1(K_2cf_MTHFR, K_NADPH_MTHFR, NADPH, Vm_MTHFR, c_2cf, sah, sam) (MM_twosubst(Vm_MTHFR, K_2cf_MTHFR, K_NADPH_MTHFR, c_2cf, NADPH)*72)/((10 + sam) - sah); end function function_4_VcMTD_1(K_1cf_MTD, K_2cf_MTD, Vf_cMTD, Vr_cMTD, c_1cf, c_2cf) MM(Vf_cMTD, K_2cf_MTD, c_2cf) - MM(Vr_cMTD, K_1cf_MTD, c_1cf); end function function_4_VcMTCH_1(K_10f_MTCH, K_1cf_MTCH, Vf_cMTCH, Vr_MTCH, c_10f, c_1cf) MM(Vf_cMTCH, K_1cf_MTCH, c_1cf) - MM(Vr_MTCH, K_10f_MTCH, c_10f); end function function_4_V_ART_1(K_10f_ART, K_aic_ART, Vm_ART, aic, c_10f) (Vm_ART*c_10f*aic)/((K_10f_ART + c_10f)*(K_aic_ART + aic)); end function function_4_V_BHMT_1(BET, H2O2, K_bet_BHMT, K_hcy_BHMT, Ki_BHMT, Vm_BHMT, cytosol, hcy, sah, sam, ssH2O2) cytosol*exp(-0.0021*(sam + sah))*exp(0.0021*102.6)*MM_twosubst(Vm_BHMT, K_hcy_BHMT, K_bet_BHMT, hcy, BET)*((ssH2O2 + Ki_BHMT)/(H2O2 + Ki_BHMT)); end function function_4_V_MATI_1(Ki_MAT1, Km_MAT1, Vm_MAT1, c_gsg, met, sam) Vm_MAT1*(met/(Km_MAT1 + met))*(0.23 + 0.8*exp(-0.0026*sam))*((Ki_MAT1 + 66.71)/(Ki_MAT1 + c_gsg)); end function function_4_V_MATIII_1(Ka_MAT3, Ki_MAT3, Km_MAT3, Vm_MAT3, c_gsg, met, sam) Vm_MAT3*(met^1.21/(Km_MAT3 + met^1.21))*(1 + (7.2*sam^2)/(Ka_MAT3^2 + sam^2))*((Ki_MAT3 + 66.71)/(Ki_MAT3 + c_gsg)); end function function_4_V_GNMT_1(K_gly_GNMT, K_sam_GNMT, Ki_GNMT, Vm_GNMT, c_5mf, c_gly, cytosol, sah, sam) cytosol*MM_twosubst(Vm_GNMT, K_sam_GNMT, K_gly_GNMT, sam, c_gly)*(1/(1 + sah/Ki_GNMT))*(4.8/(0.35 + c_5mf)); end function function_4_V_DNMT_1(Ki_DNMT, Km_DNMT, Vm_DNMT, sah, sam) Vm_DNMT*(sam/(Km_DNMT*(1 + sah/Ki_DNMT) + sam)); end function function_4_V_SAHH_1(K_hcy_SAHH, K_sah_SAHH, Vf_SAHH, Vr_SAHH, hcy, sah) MM(Vf_SAHH, K_sah_SAHH, sah) - MM(Vr_SAHH, K_hcy_SAHH, hcy); end function function_4_gluconeogenesis_ser_1(c_ser) 1.2*c_ser; end function function_4_V_CBS_1(H2O2, K_hcy_CBS, K_ser_CBS, Ka_CBS, Vm_CBS, c_ser, hcy, sah, sam, ssH2O2) MM_twosubst(Vm_CBS, K_hcy_CBS, K_ser_CBS, hcy, c_ser)*(((30/102.59)^2 + 1)/((30/(sam + sah))^2 + 1))*((H2O2 + Ka_CBS)/(ssH2O2 + Ka_CBS)); end function function_4_V_CTGL_1(K_cyt_CTGL, Vm_CTGL, cyt) (Vm_CTGL*cyt)/(K_cyt_CTGL + cyt); end function function_4_V_GCS_1(H2O2, K_cys_GCS, K_glu_GCS, Ka_GCS, Ke_GCS, Ki_GCS, Kp_GCS, Vm_GCS, c_cys, c_glu, c_gsh, glc, ssH2O2) (Vm_GCS*(c_cys*c_glu - glc/Ke_GCS))/(K_cys_GCS*K_glu_GCS + c_glu*K_cys_GCS + c_cys*(K_glu_GCS*(1 + c_gsh/Ki_GCS) + c_glu) + glc/Kp_GCS + c_gsh/Ki_GCS)*((H2O2 + Ka_GCS)/(ssH2O2 + Ka_GCS)); end function function_4_V_GS_1(K_glc_GS, K_gly_GS, Ke_GS, Kp_GS, Vm_GS, c_gly, c_gsh, glc) (Vm_GS*(c_gly*glc - c_gsh/Ke_GS))/(K_gly_GS*K_glc_GS + glc*K_gly_GS + c_gly*(K_glc_GS + glc) + c_gsh/Kp_GS); end function function_4_c_glu_usage_1(c_glu) 0.07*c_glu; end function function_4_cys_usage_1(c_cys) (0.35*c_cys^2)/200; end function function_4_V_GPX_1(H2O2, K_H2O2_GPX, K_gsh_GPX, Vm_GPX, c_gsh) Vm_GPX*(c_gsh/(K_gsh_GPX + c_gsh))^2*(H2O2/(K_H2O2_GPX + H2O2)); end function function_4_V_GR_1(K_NADPH_GR, K_gsg_GR, NADPH, Vm_GR, c_gsg) (Vm_GR*c_gsg*NADPH)/((K_gsg_GR + c_gsg)*(K_NADPH_GR + NADPH)); end function function_4_c_gsh_degr_1(c_gsh) 0.002*c_gsh; end function function_4_c_gsg_degr_1(c_gsg) 0.1*c_gsg; end function function_4_V_ODC_1(Kipodc, Kmodc, parameter_1, species_2, species_7) (parameter_1*species_7)/(Kmodc*(1 + species_2/Kipodc) + species_7); end function function_4_V_SAMDC_1(Kapsamdc, Kiasamdc, Kissamdc, Kmsamdc, parameter_3, sam, species_1, species_2, species_3) (parameter_3/(1 + species_3/Kissamdc)*sam)/(Kmsamdc*(1 + Kapsamdc/species_2 + species_1/Kiasamdc) + sam); end function function_4_V_SSAT_S_1(C, Kmaccoassat, Kmcoassat, Kmdssat, Kmsssat, parameter_2, species_3, species_4, species_8, species_9) (1/C*parameter_2*species_3*species_8)/(Kmsssat*(1 + species_4/Kmdssat)*Kmaccoassat*(1 + species_9/Kmcoassat) + Kmaccoassat*(1 + species_9/Kmcoassat)*species_3 + Kmsssat*(1 + species_4/Kmdssat)*species_8 + species_3*species_8); end function function_4_V_SSAT_D_1(Kmaccoassat, Kmcoassat, Kmdssat, Kmsssat, parameter_2, species_3, species_4, species_8, species_9) (parameter_2*species_4*species_8)/(Kmdssat*(1 + species_3/Kmsssat)*Kmaccoassat*(1 + species_9/Kmcoassat) + Kmaccoassat*(1 + species_9/Kmcoassat)*species_4 + Kmdssat*(1 + species_3/Kmsssat)*species_8 + species_4*species_8); end function function_4_V_PAO_AS_1(Kmadpao, Kmaspao, Kmdpao, Kmspao, Vmpao, species_3, species_4, species_5, species_6) (Vmpao*species_5)/(Kmaspao*(1 + species_6/Kmadpao + species_5/Kmaspao + species_4/Kmdpao + species_3/Kmspao)); end function function_4_V_PAO_AD_1(Kmadpao, Kmaspao, Kmdpao, Kmspao, Vmpao, species_3, species_4, species_5, species_6) (Vmpao*species_6)/(Kmadpao*(1 + species_6/Kmadpao + species_5/Kmaspao + species_4/Kmdpao + species_3/Kmspao)); end function function_4_V_SPDS_1(KaSpds, Kiaspds, Kidspds, Kpspds, Vmspds, species_1, species_2, species_4) (Vmspds*species_1*species_2)/(Kiaspds*Kpspds*(1 + species_4/Kidspds) + Kpspds*species_1 + KaSpds*(1 + species_4/Kidspds)*species_2 + species_1*species_2); end function function_4_V_SPMS_1(Kaspms, Kdspms, Kiaspms, Kisspms, Vmspms, species_1, species_3, species_4) (Vmspms*species_1*species_4)/(Kiaspms*Kdspms*(1 + species_3/Kisspms) + Kdspms*species_1 + Kaspms*(1 + species_3/Kisspms)*species_4 + species_1*species_4); end function function_4_V_MATII(Ki, Km, met, parameter_19, sam) parameter_19/(1 + ((Km*(1 + sam/Ki))/met)^0.76); end function function_4_V_SDH_1(K_src_SDH, K_thf_SDH, Vm_SDH, m_thf, mito, src) mito*MM_twosubst(Vm_SDH, K_thf_SDH, K_src_SDH, m_thf, src); end function function_4_V_b_GLU_c_1(K_bglutc, V_bglutc, b_glu, c_glu, cytosol, k_out_glu) cytosol*(MM(V_bglutc, K_bglutc, b_glu) - k_out_glu*c_glu); end function function_4_VmGLYc_1(K_cgly, K_mgly, V_cgly, V_mgly, c_gly, cytosol, m_gly, mito) MM(V_mgly, K_mgly, m_gly)*mito*(1/3) - MM(V_cgly, K_cgly, c_gly)*cytosol; end function function_4_V_b_SER_c_1(K_bserc, V_bserc, b_ser, c_ser, cytosol, k_out_ser) cytosol*(MM(V_bserc, K_bserc, b_ser) - k_out_ser*c_ser); end function function_4_VmSHMT_1(K_2cf_SHMT, K_gly_SHMT, K_ser_SHMT, K_thf_SHMT, Vf_mSHMT, Vr_mSHMT, m_2cf, m_gly, m_ser, m_thf) MM_twosubst(Vf_mSHMT, K_thf_SHMT, K_ser_SHMT, m_thf, m_ser) - MM_twosubst(Vr_mSHMT, K_gly_SHMT, K_2cf_SHMT, m_gly, m_2cf); end function function_4_V_c_gshHb_1(K_gshHb, V_gshHb, c_gsh, cytosol) cytosol*MM(V_gshHb, K_gshHb, c_gsh); end function function_4_V_b_MET_c_1(K_bmetc, V_bmetc, b_met, cytosol, k_out_met, met) cytosol*(MM(V_bmetc, K_bmetc, b_met) - k_out_met*met); end function function_4_V_b_GLY_c_1(K_bglyc, V_bglyc, b_gly, c_gly, cytosol, k_out_gly) cytosol*(MM(V_bglyc, K_bglyc, b_gly) - k_out_gly*c_gly); end function function_4_VmFTS_1(K_10f_mFTS, K_coo_mFTS, K_thf_mFTS, Vf_mFTS, Vr_mFTS, m_10f, m_coo, m_thf) MM_twosubst(Vf_mFTS, K_thf_mFTS, K_coo_mFTS, m_thf, m_coo) - MM(Vr_mFTS, K_10f_mFTS, m_10f); end function function_4_VmMTD_1(K_1cf_MTD, K_2cf_MTD, Vf_mMTD, Vr_MTD, m_1cf, m_2cf) MM(Vf_mMTD, K_2cf_MTD, m_2cf) - MM(Vr_MTD, K_1cf_MTD, m_1cf); end function function_4_V_DMGD_1(K_dmg_DMGD, K_thf_DMGD, Vm_DMGD, dmg, m_thf, mito) mito*MM_twosubst(Vm_DMGD, K_thf_DMGD, K_dmg_DMGD, m_thf, dmg); end function function_4_VmMTCH_1(K_10f_MTCH, K_1cf_MTCH, Vf_mMTCH, Vr_MTCH, m_10f, m_1cf) MM(Vf_mMTCH, K_1cf_MTCH, m_1cf) - MM(Vr_MTCH, K_10f_MTCH, m_10f); end function function_4_V_b_CYS_c_1(K_bcysc, V_bcysc, b_cys, cytosol) cytosol*MM(V_bcysc, K_bcysc, b_cys); end function function_4_V_c_gsgLb_1(K_gsgLb, V_gsgLb, c_gsg, cytosol) cytosol*MM(V_gsgLb, K_gsgLb, c_gsg); end function function_4_VmSERc_1(K_cser, K_mser, V_cser, V_mser, c_ser, cytosol, m_ser, mito) ((MM(V_mser, K_mser, m_ser)*mito)/3 - MM(V_cser, K_cser, c_ser))*cytosol; end function function_4_V_c_gsgHb_1(K_gsgHb, V_gsgHb, c_gsg, cytosol) cytosol*MM(V_gsgHb, K_gsgHb, c_gsg); end model *MODEL1305060001() // Compartments and Species: compartment blood, cytosol, mito, cell; species $b_met in blood, $b_ser in blood, b_gly in blood, b_glu in blood; species b_cys in blood, b_gsg in blood, b_gsh in blood, $GAR in cytosol; species $NADPH in cytosol, $BET in cytosol, $DUMP in cytosol, $H2O2 in cytosol; species c_thf in cytosol, $Fol in cell, c_5mf in cytosol, c_2cf in cytosol; species c_1cf in cytosol, c_10f in cytosol, c_dhf in cytosol, aic in cytosol; species c_glu in cytosol, c_cys in cytosol, glc in cytosol, c_gly in cytosol; species c_gsg in cytosol, c_gsh in cytosol, cyt in cytosol, hcy in cytosol; species c_ser in cytosol, sah in cytosol, sam in cytosol, met in cytosol; species c_coo in cytosol, species_1 in cytosol, species_2 in cytosol, species_3 in cytosol; species species_4 in cytosol, species_5 in cytosol, species_6 in cytosol; species $species_7 in cytosol, species_8 in cytosol, species_9 in cytosol; species $CO in mito, m_thf in mito, m_2cf in mito, m_1cf in mito, m_10f in mito; species m_ser in mito, m_gly in mito, m_coo in mito, $HCHO in cell, src in cell; species dmg in cell; // Assignment Rules: b_met := aa_input*b_met_basal; aa_input := piecewise(breakfast, 7 <= daytime && daytime <= 10, piecewise(lunch, 12 <= daytime && daytime <= 15, piecewise(dinner, 18 <= daytime && daytime <= 21, fasting))); b_ser := aa_input*b_ser_basal; tot_cfol := c_5mf + c_2cf + c_1cf + c_10f + c_dhf + c_thf; tot_mfol := m_thf + m_2cf + m_1cf + m_10f; V_oCys_b := aa_input*V_oCys_b_basal; V_oGly_b := aa_input*V_oGly_b_basal; V_oGlu_b := aa_input*V_oGlu_b_basal; daytime := time - 24*floor(time/24); parameter_14 := parameter_16; parameter_15 := 3*parameter_16; parameter_17 := species_3 + species_4; parameter_18 := 100*(parameter_16/0.24); // Rate Rules: parameter_1' = 60*(65.06/sam)*parameter_7*(1/(1 + parameter_5*(species_4 + species_3))) - parameter_6*parameter_4*parameter_1; parameter_4' = 1*parameter_13*(1 - 1/(1 + parameter_5*0.01*(species_4 + species_3))) - parameter_12*parameter_4; parameter_2' = 60*parameter_9*(1 - 1/(1 + parameter_5*(species_4 + species_3))) - parameter_8*(1/(1 + parameter_5*(species_4 + species_3)))*parameter_2; parameter_3' = 60*(65.06/sam)*parameter_11*(1/(1 + parameter_5*(species_4 + species_3))) - parameter_10*parameter_3; // Reactions: b_gsh_decomp: b_gsh -> b_cys + b_gly + b_glu; blood*function_4_b_gsh_decomp_1(b_gsh); b_gsg_decomp: b_gsg -> 2b_cys + 2b_gly + 2b_glu; blood*function_4_b_gsg_decomp_1(b_gsg); b_cys_cystine_conv: b_cys -> ; blood*function_4_b_cys_cystine_conv_1(b_cys); b_cys_loss: b_cys -> ; blood*function_4_b_cys_loss_1(b_cys); b_glu_loss: b_glu -> ; blood*function_4_b_glu_loss_1(b_glu); b_gly_loss: b_gly -> ; blood*function_4_b_gly_loss_1(b_gly); b_gsh_loss: b_gsh -> ; blood*function_4_b_gsh_loss_1(b_gsh); b_gsg_loss: b_gsg -> ; blood*function_4_b_gsg_loss_1(b_gsg); b_cys_import: -> b_cys; blood*function_1(V_oCys_b); b_gly_import: -> b_gly; blood*function_1(V_oGly_b); b_glu_import: -> b_glu; blood*function_1(V_oGlu_b); V_c_gshHb: c_gsh -> b_gsh; function_4_V_c_gshHb_1(K_gshHb, V_gshHb, c_gsh, cytosol); V_c_gshLb: c_gsh -> b_gsh; function_4_V_c_gshLb_1(K_gshLb, V_gshLb, c_gsh, cytosol, h_gshLb); V_c_gsgHb: c_gsg -> b_gsg; function_4_V_c_gsgHb_1(K_gsgHb, V_gsgHb, c_gsg, cytosol); V_c_gsgLb: c_gsg -> b_gsg; function_4_V_c_gsgLb_1(K_gsgLb, V_gsgLb, c_gsg, cytosol); V_b_CYS_c: b_cys -> c_cys; function_4_V_b_CYS_c_1(K_bcysc, V_bcysc, b_cys, cytosol); V_b_GLU_c: b_glu -> c_glu; function_4_V_b_GLU_c_1(K_bglutc, V_bglutc, b_glu, c_glu, cytosol, k_out_glu); V_b_GLY_c: b_gly -> c_gly; function_4_V_b_GLY_c_1(K_bglyc, V_bglyc, b_gly, c_gly, cytosol, k_out_gly); V_b_SER_c: $b_ser -> c_ser; function_4_V_b_SER_c_1(K_bserc, V_bserc, b_ser, c_ser, cytosol, k_out_ser); V_b_MET_c: $b_met -> met; function_4_V_b_MET_c_1(K_bmetc, V_bmetc, b_met, cytosol, k_out_met, met); VmFTD: m_10f -> m_thf; mito*function_4_VmFTD_1(K_10f_FTD, Vm_mFTD, m_10f); VmSHMT: m_thf + m_ser -> m_gly + m_2cf; mito*function_4_VmSHMT_1(K_2cf_SHMT, K_gly_SHMT, K_ser_SHMT, K_thf_SHMT, Vf_mSHMT, Vr_mSHMT, m_2cf, m_gly, m_ser, m_thf); VmFTS: m_thf + m_coo -> m_10f; mito*function_4_VmFTS_1(K_10f_mFTS, K_coo_mFTS, K_thf_mFTS, Vf_mFTS, Vr_mFTS, m_10f, m_coo, m_thf); VmNE: m_thf + $HCHO -> m_2cf; function_4_VmNE_1(HCHO, k1_mNE, k2_mNE, m_2cf, m_thf, mito); V_GDC: m_thf + m_gly -> m_2cf + $CO; mito*function_4_V_GDC_1(K_gly_GDC, K_thf_GDC, Vm_GDC, m_gly, m_thf); V_SDH: m_thf + src -> m_2cf + m_gly; function_4_V_SDH_1(K_src_SDH, K_thf_SDH, Vm_SDH, m_thf, mito, src); V_DMGD: m_thf + dmg -> m_2cf + src; function_4_V_DMGD_1(K_dmg_DMGD, K_thf_DMGD, Vm_DMGD, dmg, m_thf, mito); VmMTD: m_2cf -> m_1cf; mito*function_4_VmMTD_1(K_1cf_MTD, K_2cf_MTD, Vf_mMTD, Vr_MTD, m_1cf, m_2cf); VmMTCH: m_1cf -> m_10f; mito*function_4_VmMTCH_1(K_10f_MTCH, K_1cf_MTCH, Vf_mMTCH, Vr_MTCH, m_10f, m_1cf); VmSERc: 3m_ser -> c_ser; function_4_VmSERc_1(K_cser, K_mser, V_cser, V_mser, c_ser, cytosol, m_ser, mito); VmHCOOHc: 3m_coo -> c_coo; function_4_VmHCOOHc_1(c_coo, cytosol, k_in_coo, k_out_coo, m_coo, mito); VmGLYc: 3m_gly -> c_gly; function_4_VmGLYc_1(K_cgly, K_mgly, V_cgly, V_mgly, c_gly, cytosol, m_gly, mito); V_MS: c_5mf + hcy -> c_thf + met; cytosol*function_4_V_MS_1(H2O2, K_5mf_MS, K_hcy_MS, Ki_MS, Vm_MS, c_5mf, hcy, ssH2O2); V_DHFR: c_dhf + $NADPH -> c_thf; cytosol*function_4_V_DHFR_1(K_NADPH_DHFR, K_dhf_DHFR, NADPH, Vm_DHFR, c_dhf); VcFTD: c_10f -> c_thf; cytosol*function_4_VcFTD_1(K_10f_FTD, Vm_cFTD, c_10f); V_PGT: c_10f + $GAR -> aic + c_thf; cytosol*function_4_V_PGT_1(GAR, K_10f_PGT, K_GAR_PGT, Vm_PGT, c_10f); VcFTS: c_thf + c_coo -> c_10f; cytosol*function_4_VcFTS_1(K_coo_cFTS, K_thf_cFTS, Vm_cFTS, c_coo, c_thf); VcSHMT: c_ser + c_thf -> c_gly + c_2cf; cytosol*function_4_VcSHMT_1(K_2cf_SHMT, K_gly_SHMT, K_ser_SHMT, K_thf_SHMT, Vf_cSHMT, Vr_cSHMT, c_2cf, c_gly, c_ser, c_thf); VcNE: c_thf + $HCHO -> c_2cf; function_4_VcNE_1(HCHO, c_2cf, c_thf, cytosol, k1_cNE, k2_cNE); V_TS: $DUMP + c_2cf -> c_dhf; cytosol*function_4_V_TS_1(DUMP, K_2cf_TS, K_DUMP_TS, Vm_TS, c_2cf); V_MTHFR: c_2cf + $NADPH -> c_5mf; cytosol*function_4_V_MTHFR_1(K_2cf_MTHFR, K_NADPH_MTHFR, NADPH, Vm_MTHFR, c_2cf, sah, sam); VcMTD: c_2cf -> c_1cf + $NADPH; cytosol*function_4_VcMTD_1(K_1cf_MTD, K_2cf_MTD, Vf_cMTD, Vr_cMTD, c_1cf, c_2cf); VcMTCH: c_1cf -> c_10f; cytosol*function_4_VcMTCH_1(K_10f_MTCH, K_1cf_MTCH, Vf_cMTCH, Vr_MTCH, c_10f, c_1cf); V_ART: c_10f + aic -> c_thf; cytosol*function_4_V_ART_1(K_10f_ART, K_aic_ART, Vm_ART, aic, c_10f); V_BHMT: hcy + $BET -> met + dmg; function_4_V_BHMT_1(BET, H2O2, K_bet_BHMT, K_hcy_BHMT, Ki_BHMT, Vm_BHMT, cytosol, hcy, sah, sam, ssH2O2); V_MATI: met -> sam; cytosol*function_4_V_MATI_1(Ki_MAT1, Km_MAT1, Vm_MAT1, c_gsg, met, sam); V_MATIII: met -> sam; cytosol*function_4_V_MATIII_1(Ka_MAT3, Ki_MAT3, Km_MAT3, Vm_MAT3, c_gsg, met, sam); V_GNMT: sam + c_gly -> sah + src; function_4_V_GNMT_1(K_gly_GNMT, K_sam_GNMT, Ki_GNMT, Vm_GNMT, c_5mf, c_gly, cytosol, sah, sam); V_DNMT: sam -> sah; cytosol*function_4_V_DNMT_1(Ki_DNMT, Km_DNMT, Vm_DNMT, sah, sam); V_SAHH: sah -> hcy; cytosol*function_4_V_SAHH_1(K_hcy_SAHH, K_sah_SAHH, Vf_SAHH, Vr_SAHH, hcy, sah); gluconeogenesis_ser: c_ser -> ; cytosol*function_4_gluconeogenesis_ser_1(c_ser); V_CBS: hcy + c_ser -> cyt; cytosol*function_4_V_CBS_1(H2O2, K_hcy_CBS, K_ser_CBS, Ka_CBS, Vm_CBS, c_ser, hcy, sah, sam, ssH2O2); V_CTGL: cyt -> c_cys; cytosol*function_4_V_CTGL_1(K_cyt_CTGL, Vm_CTGL, cyt); V_GCS: c_cys + c_glu -> glc; cytosol*function_4_V_GCS_1(H2O2, K_cys_GCS, K_glu_GCS, Ka_GCS, Ke_GCS, Ki_GCS, Kp_GCS, Vm_GCS, c_cys, c_glu, c_gsh, glc, ssH2O2); cys_usage: c_cys -> ; cytosol*function_4_cys_usage_1(c_cys); c_glu_usage: c_glu -> ; cytosol*function_4_c_glu_usage_1(c_glu); V_GS: glc + c_gly -> c_gsh; cytosol*function_4_V_GS_1(K_glc_GS, K_gly_GS, Ke_GS, Kp_GS, Vm_GS, c_gly, c_gsh, glc); V_GPX: 2c_gsh + $H2O2 -> c_gsg; cytosol*function_4_V_GPX_1(H2O2, K_H2O2_GPX, K_gsh_GPX, Vm_GPX, c_gsh); V_GR: c_gsg + $NADPH -> 2c_gsh; cytosol*function_4_V_GR_1(K_NADPH_GR, K_gsg_GR, NADPH, Vm_GR, c_gsg); c_gsh_degr: c_gsh -> ; cytosol*function_4_c_gsh_degr_1(c_gsh); c_gsg_degr: c_gsg -> ; cytosol*function_4_c_gsg_degr_1(c_gsg); reaction_1: $species_7 -> species_2; cytosol*function_4_V_ODC_1(reaction_1_Kipodc, reaction_1_Kmodc, parameter_1, species_2, species_7); reaction_2: sam -> species_1; cytosol*function_4_V_SAMDC_1(reaction_2_Kapsamdc, reaction_2_Kiasamdc, reaction_2_Kissamdc, reaction_2_Kmsamdc, parameter_3, sam, species_1, species_2, species_3); reaction_3: species_3 + species_8 -> species_5 + species_9; cytosol*function_4_V_SSAT_S_1(reaction_3_C, reaction_3_Kmaccoassat, reaction_3_Kmcoassat, reaction_3_Kmdssat, reaction_3_Kmsssat, parameter_2, species_3, species_4, species_8, species_9); reaction_4: species_4 + species_8 -> species_6 + species_9; cytosol*function_4_V_SSAT_D_1(reaction_4_Kmaccoassat, reaction_4_Kmcoassat, reaction_4_Kmdssat, reaction_4_Kmsssat, parameter_2, species_3, species_4, species_8, species_9); reaction_5: species_6 -> species_2; cytosol*function_4_V_PAO_AD_1(reaction_5_Kmadpao, reaction_5_Kmaspao, reaction_5_Kmdpao, reaction_5_Kmspao, reaction_5_Vmpao, species_3, species_4, species_5, species_6); reaction_6: species_5 -> species_4; cytosol*function_4_V_PAO_AS_1(reaction_6_Kmadpao, reaction_6_Kmaspao, reaction_6_Kmdpao, reaction_6_Kmspao, reaction_6_Vmpao, species_3, species_4, species_5, species_6); reaction_7: species_1 + species_2 -> species_4; cytosol*function_4_V_SPDS_1(reaction_7_KaSpds, reaction_7_Kiaspds, reaction_7_Kidspds, reaction_7_Kpspds, reaction_7_Vmspds, species_1, species_2, species_4); reaction_8: species_1 + species_4 -> species_3; cytosol*function_4_V_SPMS_1(reaction_8_Kaspms, reaction_8_Kdspms, reaction_8_Kiaspms, reaction_8_Kisspms, reaction_8_Vmspms, species_1, species_3, species_4); reaction_9: species_8 => species_9; cytosol*parameter_15*species_8; reaction_10: species_9 => species_8; cytosol*parameter_14*species_9; reaction_11: species_2 => ; cytosol*reaction_11_k1*species_2; reaction_12: species_6 => ; cytosol*reaction_12_k1*species_6; reaction_13: met -> sam; cytosol*function_4_V_MATII(reaction_13_Ki, reaction_13_Km, met, parameter_19, sam); // Species initializations: b_gly = 218.733171504338; b_glu = 60.4651616225031; b_cys = 183.099466381356; b_gsg = 0.472632922783833; b_gsh = 12.5470655822207; GAR = 10; NADPH = 50; BET = 50; DUMP = 20; H2O2 = 0.015; c_thf = Fol/((2*3)/4) - (c_5mf + c_2cf + c_1cf + c_10f + c_dhf); Fol = 20.1; c_5mf = 5.36079859230553; c_2cf = 0.463962655701761; c_1cf = 0.259497676806752; c_10f = 3.25539505319571; c_dhf = 0.0352527196984464; aic = 0.944676738309717; c_glu = 3236.78229408139; c_cys = 179.792196767939; glc = 9.60706615144005; c_gly = 927.56013101536; c_gsg = 59.8062682413464; c_gsh = 6272.51492720171; cyt = 32.3047581589977; hcy = 1.02425194863179; c_ser = 571.225285800751; sah = 15.5626693211634; sam = 65.0613824844853; met = 50.6006924474774; c_coo = 13.9758110645557; species_1 = 0.011178638638793; species_2 = 98.2036296721139; species_3 = 61.3595114874529; species_4 = 79.5917525310194; species_5 = 0.0272742537826481; species_6 = 0.903751442137693; species_7 = 300; species_8 = 38.833390762794; species_9 = 160.666609237206; CO = 0; m_thf = Fol/((2*1)/4) - (m_2cf + m_1cf + m_10f); m_2cf = 1.66729681864136; m_1cf = 1.55022131198345; m_10f = 15.9931179032642; m_ser = 2150.05782513217; m_gly = 2043.470284255; m_coo = 58.3710073680041; HCHO = 500; src = 8.25411023033989; dmg = 0.677559463168903; // Compartment initializations: blood = 1; cytosol = 1; mito = 1; cell = 1; // Variable initializations: b_met_basal = 30; b_ser_basal = 150; V_oCys_b_basal = 70; V_oGly_b_basal = 630; V_oGlu_b_basal = 273; V_gshHb = 150; K_gshHb = 150; V_gshLb = 1100; h_gshLb = 3; K_gshLb = 3000; V_gsgHb = 40; K_gsgHb = 1250; V_gsgLb = 4025; K_gsgLb = 7100; V_bcysc = 14950; K_bcysc = 2100; V_bglutc = 28000; K_bglutc = 300; k_out_glu = 1; V_bglyc = 4600; K_bglyc = 150; k_out_gly = 1; V_bserc = 2700; K_bserc = 150; k_out_ser = 1; V_bmetc = 913.4; K_bmetc = 150; k_out_met = 1; Vm_mFTD = 1050; K_10f_FTD = 20; Vf_mSHMT = 11440; K_thf_SHMT = 50; K_ser_SHMT = 600; Vr_mSHMT = 30000000; K_gly_SHMT = 10000; K_2cf_SHMT = 3200; Vf_mFTS = 2000; K_thf_mFTS = 3; K_coo_mFTS = 43; Vr_mFTS = 6300; K_10f_mFTS = 22; k1_mNE = 0.03; k2_mNE = 20; Vm_GDC = 15000; K_thf_GDC = 50; K_gly_GDC = 3400; Vm_SDH = 15000; K_thf_SDH = 50; K_src_SDH = 320; Vm_DMGD = 15000; K_thf_DMGD = 50; K_dmg_DMGD = 50; Vf_mMTD = 180000; K_2cf_MTD = 2; Vr_MTD = 594000; K_1cf_MTD = 10; Vf_mMTCH = 790000; K_1cf_MTCH = 250; Vr_MTCH = 20000; K_10f_MTCH = 100; V_mser = 10000; K_mser = 5700; V_cser = 10000; K_cser = 5700; k_in_coo = 100; k_out_coo = 100; V_mgly = 10000; K_mgly = 5700; V_cgly = 10000; K_cgly = 5700; Vm_MS = 500; K_5mf_MS = 25; K_hcy_MS = 1; ssH2O2 = 0.01; Ki_MS = 0.01; Vm_DHFR = 2000; K_dhf_DHFR = 0.5; K_NADPH_DHFR = 4; Vm_cFTD = 500; Vm_PGT = 24300; K_10f_PGT = 4.9; K_GAR_PGT = 520; Vm_cFTS = 3900; K_thf_cFTS = 3; K_coo_cFTS = 43; Vf_cSHMT = 5200; Vr_cSHMT = 15000000; k1_cNE = 0.03; k2_cNE = 22; Vm_TS = 5000; K_DUMP_TS = 6.3; K_2cf_TS = 14; Vm_MTHFR = 5300; K_2cf_MTHFR = 50; K_NADPH_MTHFR = 16; Vf_cMTD = 80000; Vr_cMTD = 600000; Vf_cMTCH = 500000; Vm_ART = 55000; K_10f_ART = 5.9; K_aic_ART = 100; Vm_BHMT = 2160; K_hcy_BHMT = 12; K_bet_BHMT = 100; Ki_BHMT = 0.01; Vm_MAT1 = 0; Km_MAT1 = 41; Ki_MAT1 = 2140; Vm_MAT3 = 0; Km_MAT3 = 300; Ka_MAT3 = 360; Ki_MAT3 = 4030; Vm_GNMT = 260; K_sam_GNMT = 63; K_gly_GNMT = 130; Ki_GNMT = 18; Vm_DNMT = 180; Km_DNMT = 1.4; Ki_DNMT = 1.4; Vf_SAHH = 320; K_sah_SAHH = 6.5; Vr_SAHH = 4530; K_hcy_SAHH = 150; Vm_CBS = 420000; K_hcy_CBS = 1000; K_ser_CBS = 2000; Ka_CBS = 0.035; Vm_CTGL = 1500; K_cyt_CTGL = 500; Vm_GCS = 3600; Ke_GCS = 5597; K_cys_GCS = 100; K_glu_GCS = 1900; Ki_GCS = 8200; Kp_GCS = 300; Ka_GCS = 0.01; Vm_GS = 5400; Ke_GS = 5600; K_gly_GS = 300; K_glc_GS = 22; Kp_GS = 30; Vm_GPX = 4500; K_gsh_GPX = 1330; K_H2O2_GPX = 0.09; Vm_GR = 892.5; K_gsg_GR = 107; K_NADPH_GR = 10.4; dinner = 1; lunch = 1; breakfast = 1; fasting = 1; k_out_cys = 1; parameter_1 = 72.2557178994351; parameter_7 = 300; parameter_5 = 1; parameter_6 = 3; parameter_4 = 0.58497831332261; parameter_2 = 42.2853792055417; parameter_9 = 0.06; parameter_8 = 12; parameter_3 = 21.1340139923629; parameter_11 = 60; parameter_10 = 1.2; parameter_13 = 0.02; parameter_12 = 0.02; parameter_16 = 0.24; parameter_19 = 220; reaction_1_Kipodc = 1300; reaction_1_Kmodc = 60; reaction_2_Kapsamdc = 0.5; reaction_2_Kiasamdc = 2.5; reaction_2_Kissamdc = 500; reaction_2_Kmsamdc = 50; reaction_3_C = 4.44; reaction_3_Kmaccoassat = 1.5; reaction_3_Kmcoassat = 40; reaction_3_Kmdssat = 130; reaction_3_Kmsssat = 35; reaction_4_Kmaccoassat = 1.5; reaction_4_Kmcoassat = 40; reaction_4_Kmdssat = 130; reaction_4_Kmsssat = 35; reaction_5_Kmadpao = 14; reaction_5_Kmaspao = 0.6; reaction_5_Kmdpao = 50; reaction_5_Kmspao = 15; reaction_5_Vmpao = 621; reaction_6_Kmadpao = 14; reaction_6_Kmaspao = 0.6; reaction_6_Kmdpao = 50; reaction_6_Kmspao = 15; reaction_6_Vmpao = 621; reaction_7_KaSpds = 0.3; reaction_7_Kiaspds = 0.8; reaction_7_Kidspds = 100; reaction_7_Kpspds = 40; reaction_7_Vmspds = 657; reaction_8_Kaspms = 0.1; reaction_8_Kdspms = 60; reaction_8_Kiaspms = 0.06; reaction_8_Kisspms = 25; reaction_8_Vmspms = 193.8; reaction_11_k1 = 0.6; reaction_12_k1 = 0.6; reaction_13_Ki = 50; reaction_13_Km = 4; // Other declarations: var aa_input, tot_cfol, tot_mfol, V_oCys_b, V_oGly_b, V_oGlu_b, daytime; var parameter_1, parameter_4, parameter_2, parameter_3, parameter_14, parameter_15; var parameter_17, parameter_18; const blood, cytosol, mito, cell, b_met_basal, b_ser_basal, V_oCys_b_basal; const V_oGly_b_basal, V_oGlu_b_basal, V_gshHb, K_gshHb, V_gshLb, h_gshLb; const K_gshLb, V_gsgHb, K_gsgHb, V_gsgLb, K_gsgLb, V_bcysc, K_bcysc, V_bglutc; const K_bglutc, k_out_glu, V_bglyc, K_bglyc, k_out_gly, V_bserc, K_bserc; const k_out_ser, V_bmetc, K_bmetc, k_out_met, Vm_mFTD, K_10f_FTD, Vf_mSHMT; const K_thf_SHMT, K_ser_SHMT, Vr_mSHMT, K_gly_SHMT, K_2cf_SHMT, Vf_mFTS; const K_thf_mFTS, K_coo_mFTS, Vr_mFTS, K_10f_mFTS, k1_mNE, k2_mNE, Vm_GDC; const K_thf_GDC, K_gly_GDC, Vm_SDH, K_thf_SDH, K_src_SDH, Vm_DMGD, K_thf_DMGD; const K_dmg_DMGD, Vf_mMTD, K_2cf_MTD, Vr_MTD, K_1cf_MTD, Vf_mMTCH, K_1cf_MTCH; const Vr_MTCH, K_10f_MTCH, V_mser, K_mser, V_cser, K_cser, k_in_coo, k_out_coo; const V_mgly, K_mgly, V_cgly, K_cgly, Vm_MS, K_5mf_MS, K_hcy_MS, ssH2O2; const Ki_MS, Vm_DHFR, K_dhf_DHFR, K_NADPH_DHFR, Vm_cFTD, Vm_PGT, K_10f_PGT; const K_GAR_PGT, Vm_cFTS, K_thf_cFTS, K_coo_cFTS, Vf_cSHMT, Vr_cSHMT, k1_cNE; const k2_cNE, Vm_TS, K_DUMP_TS, K_2cf_TS, Vm_MTHFR, K_2cf_MTHFR, K_NADPH_MTHFR; const Vf_cMTD, Vr_cMTD, Vf_cMTCH, Vm_ART, K_10f_ART, K_aic_ART, Vm_BHMT; const K_hcy_BHMT, K_bet_BHMT, Ki_BHMT, Vm_MAT1, Km_MAT1, Ki_MAT1, Vm_MAT3; const Km_MAT3, Ka_MAT3, Ki_MAT3, Vm_GNMT, K_sam_GNMT, K_gly_GNMT, Ki_GNMT; const Vm_DNMT, Km_DNMT, Ki_DNMT, Vf_SAHH, K_sah_SAHH, Vr_SAHH, K_hcy_SAHH; const Vm_CBS, K_hcy_CBS, K_ser_CBS, Ka_CBS, Vm_CTGL, K_cyt_CTGL, Vm_GCS; const Ke_GCS, K_cys_GCS, K_glu_GCS, Ki_GCS, Kp_GCS, Ka_GCS, Vm_GS, Ke_GS; const K_gly_GS, K_glc_GS, Kp_GS, Vm_GPX, K_gsh_GPX, K_H2O2_GPX, Vm_GR, K_gsg_GR; const K_NADPH_GR, dinner, lunch, breakfast, fasting, k_out_cys, parameter_7; const parameter_5, parameter_6, parameter_9, parameter_8, parameter_11; const parameter_10, parameter_13, parameter_12, parameter_16, parameter_19; // Unit definitions: unit time_unit = 3600 second; unit substance = 1e-6 mole; // Display Names: mito is "mitochondrion"; b_met is "b_Methionine"; aa_input is "Aminoacid_input"; b_ser is "b_Serine"; b_gly is "b_Glycine"; b_glu is "b_Glutamate"; b_cys is "b_Cysteine"; b_gsg is "b_GSSG"; b_gsh is "b_GSH"; BET is "Betaine"; DUMP is "dUMP"; c_thf is "c_THF"; Fol is "Folate"; c_5mf is "c_5-methyl-THF"; c_2cf is "c_5-10-methylene-THF"; c_1cf is "c_5-10-methenyl-THF"; c_10f is "c_10-formyl-THF"; c_dhf is "c_DHF"; aic is "AICAR"; c_glu is "c_Glutamate"; c_cys is "c_Cysteine"; glc is "Glutamyl-Cysteine"; c_gly is "c_Glycine"; c_gsg is "c_GSSG"; c_gsh is "c_GSH"; cyt is "Cystathionine"; hcy is "Homocysteine"; c_ser is "c_Serine"; sah is "SAH"; sam is "SAM"; met is "c_Methionine"; c_coo is "c_Formate"; species_1 is "dcSAM"; species_2 is "Putrescine"; species_3 is "Spermine"; species_4 is "Spermidine"; species_5 is "Acetylspermine"; species_6 is "Acetylspermidine"; species_7 is "Ornithine"; species_8 is "Acetyl-CoA"; species_9 is "CoA"; CO is "CO2"; m_thf is "m_THF"; m_2cf is "m_5-10-methylene-THF"; m_1cf is "m_5-10-methenyl-THF"; m_10f is "m_10-formyl-THF"; m_ser is "m_Serine"; m_gly is "m_Glycine"; m_coo is "m_Formate"; HCHO is "Formaldehyde"; src is "Sarcosine"; dmg is "Dimethylglycine"; parameter_1 is "Vm_ODC"; parameter_7 is "Ks_ODC"; parameter_5 is "Ke_POL"; parameter_6 is "Kd_ODC"; parameter_4 is "ANTZ"; parameter_2 is "Vm_SSAT"; parameter_9 is "Ks_SSAT"; parameter_8 is "Kd_SSAT"; parameter_3 is "Vm_SAMDC"; parameter_11 is "Ks_SAMDC"; parameter_10 is "Kd_SAMDC"; parameter_13 is "Ks_ANTZ"; parameter_12 is "Kd_ANTZ"; parameter_14 is "K_accoa"; parameter_16 is "R"; parameter_15 is "K_coa"; parameter_17 is "S+D"; parameter_18 is "R_percent"; parameter_19 is "Vm_MATII"; reaction_1 is "V_ODC"; reaction_2 is "V_SAMDC"; reaction_3 is "V_SSAT_S"; reaction_4 is "V_SSAT_D"; reaction_5 is "V_PAO_AD"; reaction_6 is "V_PAO_AS"; reaction_7 is "V_SPDS"; reaction_8 is "V_SPMS"; reaction_9 is "V_COA"; reaction_10 is "V_ACCOA"; reaction_11 is "V_PUT_efflux"; reaction_12 is "V_AD_efflux"; reaction_13 is "V_MATII"; end