#maheshvare1

FIX: cpep_ext glc_ext h h2o ins_ext lac_ext pyr_mito

#reactions
ATP_ADP_CHANGE:
 $pool = {1.0}atp
  cyto * NUCLEOTIDE_CHANGE_Vm * (atp_adp_ss - atp_adp)
ATPconsumption:
 {1.0}atp + {1.0}h2o = {1.0}adp + {1.0}h
  cyto * ATPconsumption_Vm * (atp / ATPconsumption_KMatp / (1 + atp / ATPconsumption_KMatp))
ATPformation:
 {1.0}adp + {1.0}h = {1.0}atp + {1.0}h2o
  cyto * ATPformation_Vm * (adp * phos / (ATPformation_KMadp * ATPformation_KMphos) / ((1 + adp / ATPformation_KMadp) * (1 + phos / ATPformation_KMphos)))
ENO:
 {1.0}pg2 = {1.0}pep + {1.0}h2o
  cyto * ENO_Vm * 1 / ENO_KMpg2 * ((pg2 - pep / ENO_Keq) / (1 + pg2 / ENO_KMpg2 + 1 + pep / ENO_KMpep - 1))
FBA:
 {1.0}fbp = {1.0}dhap + {1.0}grap
  cyto * FBA_Vm * 1 / FBA_KMfbp * ((fbp - dhap * grap / FBA_Keq) / (1 + fbp / FBA_KMfbp + (1 + dhap / FBA_KMdhap) * (1 + grap / FBA_KMgrap) - 1))
FBP:
 {1.0}fbp + {1.0}h2o = {1.0}f6p
  cyto * FBP_Vm * (fbp / FBP_KMfbp / (1 + fbp / FBP_KMfbp))
FBP26:
 {1.0}f26bp + {1.0}h2o = {1.0}f6p
  cyto * FBP26_Vm * (f26bp / FBP26_KMf26bp / (1 + f26bp / FBP26_KMf26bp))
GAPD:
 {1.0}grap = {1.0}bpg13 + {1.0}h
  cyto * GAPD_Vm * 1 / (GAPD_KMgrap * GAPD_KMphos * GAPD_KMnad) * ((grap * phos * nad - bpg13 * nadh / GAPD_Keq) / ((1 + grap / GAPD_KMgrap) * (1 + phos / GAPD_KMphos) * (1 + nad / GAPD_KMnad) + (1 + bpg13 / GAPD_KMbpg13) * (1 + nadh / GAPD_KMnadh) - 1))
GLCt1r:
 {1.0}glc_ext = {1.0}glc
  cyto * GLCt1r_Vm * 1 / GLCt1r_KMglc_ext * ((glc_ext - glc / GLCt1r_Keq) / (1 + glc_ext / GLCt1r_KMglc_ext + 1 + glc / GLCt1r_KMglc - 1))
HEX1:
 {1.0}glc + {1.0}atp = {1.0}g6p + {1.0}adp + {1.0}h
  cyto * HEX1_Vm * 1 / (HEX1_KMglc * HEX1_KMatp) * ((glc * atp - g6p * adp / HEX1_Keq) / ((1 + glc / HEX1_KMglc) * (1 + atp / HEX1_KMatp) + (1 + g6p / HEX1_KMg6p) * (1 + adp / HEX1_KMadp) - 1))
IRS:
 $pool = {1.0}ins_ext + {1.0}cpep_ext
  cyto * (IRS_ss + IRS_fp)
LDH_L:
 {1.0}pyr + {1.0}h = {1.0}lac
  cyto * LDH_L_Vm * 1 / (LDH_L_KMpyr * LDH_L_KMnadh) * ((pyr * nadh - lac * nad / LDH_L_Keq) / ((1 + pyr / LDH_L_KMpyr) * (1 + nadh / LDH_L_KMnadh) + (1 + lac / LDH_L_KMlac) * (1 + nad / LDH_L_KMnad) - 1))
L_LACt2r:
 {1.0}lac = {1.0}lac_ext
  cyto * L_LACt2r_Vm * (lac / L_LACt2r_KMlac / (1 + lac / L_LACt2r_KMlac))
PFK:
 {1.0}f6p + {1.0}atp = {1.0}adp + {1.0}fbp + {1.0}h
  cyto * PFK_Vm * (f6p * atp / (PFK_KMf6p * PFK_KMatp) / ((1 + f6p / PFK_KMf6p) * (1 + atp / PFK_KMatp)))
PFK26:
 {1.0}atp + {1.0}f6p = {1.0}adp + {1.0}f26bp + {1.0}h
  cyto * PFK26_Vm * (atp * f6p / (PFK26_KMatp * PFK26_KMf6p) / ((1 + atp / PFK26_KMatp) * (1 + f6p / PFK26_KMf6p)))
PGI:
 {1.0}g6p = {1.0}f6p
  cyto * PGI_Vm * 1 / PGI_KMg6p * ((g6p - f6p / PGI_Keq) / (1 + g6p / PGI_KMg6p + 1 + f6p / PGI_KMf6p - 1))
PGK:
 {1.0}adp + {1.0}bpg13 = {1.0}atp + {1.0}pg3
  cyto * PGK_Vm * 1 / (PGK_KMadp * PGK_KMbpg13) * ((adp * bpg13 - atp * pg3 / PGK_Keq) / ((1 + adp / PGK_KMadp) * (1 + bpg13 / PGK_KMbpg13) + (1 + atp / PGK_KMatp) * (1 + pg3 / PGK_KMpg3) - 1))
PGM:
 {1.0}pg3 = {1.0}pg2
  cyto * PGM_Vm * 1 / PGM_KMpg3 * ((pg3 - pg2 / PGM_Keq) / (1 + pg3 / PGM_KMpg3 + 1 + pg2 / PGM_KMpg2 - 1))
PYK:
 {1.0}pep + {1.0}adp + {1.0}h = {1.0}pyr + {1.0}atp
  cyto * PYK_Vm * 1 / (PYK_KMpep * PYK_KMadp) * ((pep * adp - pyr * atp / PYK_Keq) / ((1 + pep / PYK_KMpep) * (1 + adp / PYK_KMadp) + (1 + pyr / PYK_KMpyr) * (1 + atp / PYK_KMatp) - 1))
PYRt2r:
 {1.0}pyr = {1.0}pyr_mito
  cyto * PYRt2r_Vm * (pyr / PYRt2r_KMpyr / (1 + pyr / PYRt2r_KMpyr))
TPI:
 {1.0}dhap = {1.0}grap
  cyto * TPI_Vm * 1 / TPI_KMdhap * ((dhap - grap / TPI_Keq) / (1 + dhap / TPI_KMdhap + 1 + grap / TPI_KMgrap - 1))


#parameters
ATPconsumption_KMatp = 2.0
ATPconsumption_Vm = 5.58245
ATPformation_KMadp = 5.6
ATPformation_KMphos = 3.4
ATPformation_Vm = 42.6819
ENO_KMpep = 0.089
ENO_KMpg2 = 0.3
ENO_Keq = 4.38534496525434
ENO_Vm = 191.263
FBA_KMdhap = 0.38
FBA_KMfbp = 0.027
FBA_KMgrap = 0.32
FBA_Keq = 0.000133163971260293
FBA_Vm = 500.562
FBP26_KMf26bp = 0.013
FBP26_Vm = 8.05946
FBP_KMfbp = 0.1
FBP_Vm = 0.01
GAPD_KMbpg13 = 0.018
GAPD_KMgrap = 0.07
GAPD_KMnad = 0.75
GAPD_KMnadh = 0.012
GAPD_KMphos = 3.4
GAPD_Keq = 0.497383227406177
GAPD_Vm = 4950.28
GLCt1r_KMglc = 17.0
GLCt1r_KMglc_ext = 17.0
GLCt1r_Keq = 1.0
GLCt1r_Vm = 1000.0
HEX1_KMadp = 0.63
HEX1_KMatp = 0.63
HEX1_KMg6p = 19.9
HEX1_KMglc = 5.0
HEX1_Keq = 2255.52682196071
HEX1_Vm = 2.71005
IRSfp_Kdatp_dt = 0.0003
IRSfp_Vm = 0.05
IRSss_Katp_ratio = 5.13347666690148
IRSss_Vm = 0.02
IRSss_hillatp_ratio = 7.10527645078065
LDH_L_KMlac = 3.0
LDH_L_KMnad = 0.211
LDH_L_KMnadh = 0.0107
LDH_L_KMpyr = 0.398
LDH_L_Keq = 100.0
LDH_L_Vm = 7.26844
L_LACt2r_KMlac = 0.8
L_LACt2r_Vm = 5.21331
NUCLEOTIDE_CHANGE_Vm = 0.2
PFK26_KMatp = 0.328
PFK26_KMf6p = 0.017
PFK26_Vm = 4.19328
PFK_KMatp = 0.063
PFK_KMf6p = 0.35
PFK_Vm = 7.48024
PGI_KMf6p = 0.12
PGI_KMg6p = 0.35
PGI_Keq = 0.364659218171184
PGI_Vm = 4525.64
PGK_KMadp = 0.126
PGK_KMatp = 0.24
PGK_KMbpg13 = 0.042
PGK_KMpg3 = 0.27
PGK_Keq = 1931.283
PGK_Vm = 4912.9
PGM_KMpg2 = 0.139
PGM_KMpg3 = 0.22
PGM_Keq = 0.174472843901766
PGM_Vm = 5000.0
PYK_KMadp = 0.22
PYK_KMatp = 0.86
PYK_KMpep = 0.18
PYK_KMpyr = 3.0
PYK_Keq = 20593.3056361955
PYK_Vm = 7.44078
PYRt2r_KMpyr = 0.15
PYRt2r_Vm = 0.0575902
TPI_KMdhap = 0.62
TPI_KMgrap = 0.55
TPI_Keq = 0.113860326083997
TPI_Vm = 4572.25
f_scale = 1.0
presim_duration = 60.0
presim_glc_ext = 3.0
sim_glc_ext = 3.0
cpep_ext = 0.0
glc_ext = 2.8
h = 1.0
h2o = 1.0
ins_ext = 6e-08
lac_ext = 1.0
pyr_mito = 1.0
cell = 0.001321
mm = 1.0
pm = 1.0


#initial values
adp = 1.199
atp = 3.921
bpg13 = 0.018
dhap = 0.011
f26bp = 0.002
f6p = 0.008
fbp = 0.019
g6p = 0.113
glc = 2.571
grap = 0.003
lac = 1.083
pep = 0.477
pg2 = 0.14
pg3 = 0.669
pyr = 0.392


#assignment rules
!F ext = 1000.0 * cell
!F cyto = 0.95 * cell
!F mito = 0.05 * cell
!F atp_adp = atp + adp
!F atp_ratio = atp / (adp + 1e-8)
!F nadh_nad = nadh + nad
!F nadh_ratio = nadh / (nad + 1e-8)
!F fbp_grap = fbp + grap
!F fbp_dhap_grap = fbp + dhap + grap
!F fbp_dhap = fbp + dhap
!F lac_pyr_ratio = lac / pyr
!F phos = piecewise(10.1746465657385, lt(glc_ext, 2.4), 10.1746465657385 + -0.184822580052604 * (glc_ext - 2.4), and(geq(glc_ext, 2.4), lt(glc_ext, 4.0)), 9.87893043765431 + -0.184822580052604 * (glc_ext - 4.0), and(geq(glc_ext, 4.0), lt(glc_ext, 8.6)), 9.02874656941233 + -0.184822580052604 * (glc_ext - 8.6), and(geq(glc_ext, 8.6), lt(glc_ext, 14.5)), 7.93829334710197 + -0.184822580052604 * (glc_ext - 14.5), and(geq(glc_ext, 14.5), lt(glc_ext, 16.0)), 7.66105947702306, geq(glc_ext, 16.0), 0.0)
!F nad = 0.3 * (pow(glc_ext, 1.39) / (pow(glc_ext, 1.39) + pow(5.32, 1.39))) + 0.59
!F nadh = 0.23 * (pow(glc_ext, 1.53) / (pow(glc_ext, 1.53) + pow(9.13, 1.53))) + 0.13
!F datp_dt = ATPformation - ATPconsumption + PGK + PYK - PFK26 - HEX1 - PFK + ATP_ADP_CHANGE
!F IRS_per_vol = IRS / cell
!F atp_adp_ss = 1.87 * (pow(glc_ext, 2.03) / (pow(glc_ext, 2.03) + pow(4.01, 2.03))) + 4.66
!F IRS_ss = IRSss_Vm * (pow(atp / adp, IRSss_hillatp_ratio) / (pow(atp / adp, IRSss_hillatp_ratio) + pow(IRSss_Katp_ratio, IRSss_hillatp_ratio)))
!F IRS_fp = piecewise(IRSfp_Vm * datp_dt / (datp_dt + IRSfp_Kdatp_dt), gt(datp_dt, 0.0), 0.0)