#xu

FIX: F_ffa M_alan PKb

#reactions
Jg10:
 {1.0}R2C2 + {2.0}cAMP = {1.0}R2_C_cAMP2 + {1.0}Cvar
  kgc1 * R2C2 * pow(cAMP, 2) - k_gc1 * R2_C_cAMP2 * Cvar
Jg11:
 {1.0}R2_C_cAMP2 + {2.0}cAMP = {1.0}R2_cAMP4 + {1.0}Cvar
  kgc2 * R2_C_cAMP2 * pow(cAMP, 2) - k_gc2 * R2_cAMP4 * Cvar
Jg3:
 $pool = {1.0}PKa
  kg3 * Cvar * (kt - PKa) / (kmg3 + (kt - PKa))
Jg4:
 {1.0}PKa = $pool
  kg4 * (PP1 + PP1_GPa) * PKa / (kmg4 + PKa)
Jg5:
 $pool = {1.0}GPa
  kg5 * PKa * (pt - GPa) / (kmg5s + (pt - GPa))
Jg6:
 {1.0}GPa = $pool
  kg6 * (PP1 + PP1_GPa) * GPa / (kmg6s + GPa)
Jg7:
 {1.0}GSa = $pool
  kg7 * (PKa + Cvar) * GSa / (kmg7s + GSa)
Jg8:
 $pool = {1.0}GSa
  kg8 * PP1 * (st - GSa) / (kmg8s + (st - GSa))
Jg9:
 {1.0}PP1 + {1.0}GPa = {1.0}PP1_GPa
  ka * PP1 * GPa - k_a * PP1_GPa
v_F1:
 {1.0}F_g6p = {1.0}F_acyl
  k_f1 * F_g6p * (1 + pow(B_ins, ep14) / (pow(k_Dins, ep14) + pow(B_ins, ep14)))
v_F3:
 {1.0}F_acyl = {1.0}F_TG
  k_f3 * F_acyl * (1 + pow(B_ins, ep15) / (pow(k_Dins, ep15) + pow(B_ins, ep15)))
v_F4:
 {1.0}F_TG = {1.0}F_ffa
  k_f4 * F_TG * pow(k_Dins, en12) / (pow(k_Dins, en12) + pow(B_ins, en12))
v_F5:
 {1.0}F_ffa = {1.0}F_acyl
  k_f5 * pow(F_ffa, 3)
v_Ggluc:
 {1.0}B_glucgn = $pool
  k1glucgn * pow(B_gluc, ng) / (pow(k_mGlgn, ng) + pow(B_gluc, ng))
v_Igluc:
 $pool = {1.0}B_ins
  k1ins * pow(B_gluc, ni) / (pow(k_mIns, ni) + pow(B_gluc, ni))
v_L10:
 {1.0}aK = {1.0}malate
  k_L10 * aK
v_L11f:
 {1.0}oa_m = {1.0}malate
  k_L11f * oa_m * (1 + pow(B_glucgn, ep5) / (pow(k_Dglucgn, ep5) + pow(B_glucgn, ep5)))
v_L11r:
 {1.0}malate = {1.0}oa_m
  k_L11r * malate
v_L12:
 {1.0}malate = {1.0}oa_c
  k_L12 * malate * pow(k_Dins, en4) / (pow(k_Dins, en4) + pow(B_ins, en4)) * (1 + pow(B_glucgn, ep6) / (pow(k_Dglucgn, ep6) + pow(B_glucgn, ep6)))
v_L13:
 {1.0}oa_c = {1.0}pep
  k_L13 * oa_c * (1 + pow(B_glucgn, ep7) / (pow(k_Dglucgn, ep7) + pow(B_glucgn, ep7))) * pow(k_Dins, en5) / (pow(k_Dins, en5) + pow(B_ins, en5))
v_L14:
 {1.0}citrate = {1.0}oa_c + {1.0}acet_c
  k_L14 * citrate * (1 + pow(B_ins, ep10) / (pow(k_Dins, ep10) + pow(B_ins, ep10))) * pow(k_Dglucgn, en7) / (pow(k_Dglucgn, en7) + pow(B_glucgn, en7))
v_L15:
 {1.0}acet_c = {1.0}malonyl
  k_L15 * acet_c * (1 + p1 * citrate / (k_p1 + citrate)) * k_i5 / (k_i5 + palmCoA)
v_L16:
 {1.0}acet_c + {7.0}malonyl = {1.0}palm
  k_L16 * acet_c * pow(malonyl, 7)
v_L17:
 {1.0}palm = {1.0}palmCoA
  k_L17 * palm * k_i1 / (k_i1 + malonyl)
v_L18:
 {1.0}palmCoA = {8.0}acet_m
  k_L18 * palmCoA * k_i2 / (k_i2 + malonyl)
v_L19:
 {2.0}acet_m = {1.0}ket
  k_L19 * pow(acet_m, 2) * (1 + pow(cAMP, ep11) / (pow(k_dcAMP, ep11) + pow(cAMP, ep11))) * pow(k_Dins, en8) / (pow(k_Dins, en8) + pow(B_ins, en8))
v_L1f:
 {1.0}gluc = {1.0}g6p
  k_L1f * gluc / (k_mL1f + gluc) * (1 + pow(B_ins, ep1) / (pow(k_Dins, ep1) + pow(B_ins, ep1)))
v_L1r:
 {1.0}g6p = {1.0}gluc
  k_L1r * g6p / (k_mL1r + g6p) * (1 + pow(B_glucgn, ep9) / (pow(k_Dglucgn, ep9) + pow(B_glucgn, ep9)))
v_L20:
 {1.0}alan = {1.0}pyr
  k_L20 * alan * pow(k_Dins2, en3) / (pow(k_Dins2, en3) + pow(B_ins, en3))
v_L21f:
 {1.0}pyr + {1.0}glutamate = {1.0}alan + {1.0}aK
  k_L21f * pyr / (k_mL21p + pyr) * glutamate / (k_mL21g + glutamate) * pow(k_Dins, en3) / (pow(k_Dins, en3) + pow(B_ins, en3))
v_L21r:
 {1.0}alan + {1.0}aK = {1.0}pyr + {1.0}glutamate
  k_L21r * alan / (k_mL21a + alan) * aK / (k_mL21k + aK) * acet_m * (pow(k_Dins, en3) / (pow(k_Dins, en3) + pow(B_ins, en3)))
v_L22:
 {1.0}glutamate = $pool
  k_L22 * glutamate
v_L2f:
 {1.0}g6p = {1.0}glycgn
  k_L2f * GSa * g6p / (k_mL2f + g6p)
v_L2r:
 {1.0}glycgn = {1.0}g6p
  k_L2r * GPa * glycgn / (k_mL2r + glycgn)
v_L3f:
 {1.0}g6p = {2.0}pep
  k_L3f * g6p / (k_mL3f + g6p) * (1 + pow(B_ins, ep2) / (pow(k_Dins, ep2) + pow(B_ins, ep2))) * pow(k_Dglucgn, en1) / (pow(k_Dglucgn, en1) + pow(B_glucgn, en1))
v_L3r:
 {2.0}pep = {1.0}g6p
  k_L3r * pep / (k_mL3r + pep) * (1 + pow(B_glucgn, ep8) / (pow(k_Dglucgn, ep8) + pow(B_glucgn, ep8))) * pow(k_Dins2, en6) / (pow(k_Dins2, en6) + pow(B_ins, en6))
v_L4:
 {1.0}pep = {1.0}pyr
  k_L4 * pep / (k_mL4 + pep) * (1 + pow(B_ins, ep3) / (pow(k_Dins, ep3) + pow(B_ins, ep3))) * pow(k_Dglucgn, en2) / (pow(k_Dglucgn, en2) + pow(B_glucgn, en2)) * k_i13 / (k_i13 + alan)
v_L5f:
 {1.0}pyr = {1.0}lac
  k_L5f * pyr / (k_mL5f + pyr)
v_L5r:
 {1.0}lac = {1.0}pyr
  k_L5r * lac / (k_mL5r + lac)
v_L6:
 {1.0}pyr = {1.0}oa_m
  k_L6 * pyr / (k_mL6 + pyr) * (1 + p2 * acet_m / (k_p2 + acet_m)) * (1 + pow(B_glucgn, ep4) / (pow(k_Dglucgn, ep4) + pow(B_glucgn, ep4)))
v_L7:
 {1.0}pyr = {1.0}acet_m
  k_L7 * pyr / (k_mL7 + pyr) * k_i8 / (k_i8 + acet_m)
v_L8:
 {1.0}oa_m + {1.0}acet_m = {1.0}citrate
  k_L8 * oa_m * acet_m * k_i4 / (k_i4 + palmCoA)
v_L9:
 {1.0}citrate = {1.0}aK
  k_L9 * citrate
v_S1f:
 {1.0}M_g6p = {1.0}M_glycgn
  k_s1f * M_g6p
v_S1r:
 {1.0}M_glycgn = {1.0}M_g6p
  k_s1r * M_glycgn
v_S2:
 {1.0}M_g6p = {2.0}M_pyr
  k_s2 * M_g6p
v_S3f:
 {1.0}M_pyr = {1.0}M_lac
  k_s3f * M_pyr
v_S3r:
 {1.0}M_lac = {1.0}M_pyr
  k_s3r * M_lac
v_S4f:
 {1.0}M_pyr = {1.0}M_alan
  k_s4f * M_pyr
v_S4r:
 {1.0}M_alan = {1.0}M_pyr
  k_s4r * M_alan * M_ket
v_c1cAMP:
 $pool = {1.0}cAMP
  kc1 * pow(B_glucgn, ng) / (pow(kcm1, ng) + pow(B_glucgn, ng))
v_c2cAMP:
 {1.0}cAMP = $pool
  kc2 * pow(B_ins, ni) / (pow(kcm2, ni) + pow(B_ins, ni)) * cAMP
v_d_Balan:
 {1.0}B_alan = $pool
  kd_Balan * B_alan
v_d_Bffa:
 {1.0}B_ffa = $pool
  kd_Bffa * B_ffa
v_d_Bgluc:
 {1.0}B_gluc = $pool
  kd_Bgluc * B_gluc
v_d_Bglucgn:
 {1.0}B_glucgn = $pool
  kd_Bglucgn * B_glucgn
v_d_Bins:
 {1.0}B_ins = $pool
  kd_Bins * B_ins
v_d_Bket:
 {1.0}B_ket = $pool
  kd_Bket * B_ket
v_d_Blac:
 {1.0}B_lac = $pool
  kd_Blac * B_lac
v_feed:
 $pool = {1.0}B_gluc
  piecewise(kf, lt(time, 20000), kresume, gt(time, tresume), 1 / (1 / (kf * (2 * pi)**0.5) * (2 * pi)**0.5) * exp(-((0.014 * (time - 20000))**2) / (2 * (1 / (kf * (2 * pi)**0.5))**2)))
v_glucgn:
 $pool = {1.0}B_glucgn
  k_glucgn
v_ins:
 $pool = {1.0}B_ins
  k_ins
v_s_dket:
 {1.0}M_ket = $pool
  ks_dket * M_ket
v_tF1:
 {1.0}B_gluc = {1.0}F_g6p
  k_tF1 * B_gluc * (1 + pow(B_ins, ep12) / (pow(k_Dins, ep12) + pow(B_ins, ep12)))
v_tF3:
 {1.0}F_ffa = {1.0}B_ffa
  k_tF3 * pow(F_ffa, 8) * pow(k_Dins2, en9) / (pow(k_Dins2, en9) + pow(B_ins, en9))
v_tL1:
 {1.0}B_gluc = {1.0}gluc
  k_tL1 * (B_gluc - gluc)
v_tL2:
 {1.0}B_lac = {1.0}lac
  k_tL2 * B_lac
v_tL3:
 {1.0}ket = {1.0}B_ket
  k_tL3 * ket
v_tL5:
 {1.0}B_ffa = {1.0}palm
  k_tL5 * B_ffa
v_tL6:
 {1.0}B_alan = {1.0}alan
  k_tL6 * B_alan * (pow(k_Dins2, en10) / (pow(k_Dins2, en10) + pow(B_ins, en10)))
v_tS1:
 {1.0}B_gluc = {1.0}M_g6p
  k_tS1 * B_gluc * (1 + pow(B_ins, ep13) / (pow(k_Dins, ep13) + pow(B_ins, ep13)))
v_tS2:
 {1.0}B_ket = {1.0}M_ket
  k_tS2 * B_ket
v_tS3:
 {1.0}M_lac = {1.0}B_lac
  k_tS3 * M_lac
v_tS4:
 {1.0}M_alan = {1.0}B_alan
  k_tS4 * M_alan * pow(k_Dins2, en11) / (pow(k_Dins2, en11) + pow(B_ins, en11))


#parameters
Gmax = 5e-08
Gmin = 3e-08
Imax = 1.3e-06
Imin = 7e-07
PP1t = 0.00025
c0 = 5.0
capkt = 0.00025
cmax = 0.0032
cmin = 2e-06
en1 = 10.0
en10 = 10.0
en11 = 10.0
en12 = 10.0
en2 = 10.0
en3 = 10.0
en4 = 10.0
en5 = 10.0
en6 = 10.0
en7 = 10.0
en8 = 10.0
en9 = 20.0
ep1 = 10.0
ep10 = 10.0
ep11 = 10.0
ep12 = 10.0
ep13 = 10.0
ep14 = 10.0
ep15 = 10.0
ep2 = 10.0
ep3 = 10.0
ep4 = 10.0
ep5 = 10.0
ep6 = 10.0
ep7 = 10.0
ep8 = 10.0
ep9 = 10.0
index = 5.0
k11 = 4.3e-05
k22 = 0.0007
k_Dglucgn = 4e-08
k_Dins = 1e-06
k_Dins2 = 7.5e-07
k_L10 = 0.1
k_L11f = 0.6
k_L11r = 0.01
k_L12 = 0.6
k_L13 = 0.5
k_L14 = 0.01
k_L15 = 0.01
k_L16 = 0.01
k_L17 = 0.01
k_L18 = 0.01
k_L19 = 0.01
k_L1f = 3.0
k_L1r = 4.0
k_L20 = 0.2
k_L21f = 0.001
k_L21r = 0.2
k_L22 = 0.01
k_L2f = 200.0
k_L2r = 20.0
k_L3f = 0.1
k_L3r = 0.3
k_L4 = 2.0
k_L5f = 0.0
k_L5r = 0.1
k_L6 = 1.0
k_L7 = 1.0
k_L8 = 0.1
k_L9 = 0.1
k_a = 60.0
k_dcAMP = 3.16227e-06
k_f1 = 0.1
k_f3 = 0.2
k_f4 = 0.1
k_f5 = 0.1
k_gc1 = 60000.0
k_gc2 = 60000.0
k_i1 = 0.1
k_i13 = 2.0
k_i2 = 1.0
k_i4 = 3.0
k_i5 = 1.0
k_i8 = 2.0
k_mGlgn = 8.0
k_mIns = 8.0
k_mL1f = 7.7
k_mL1r = 1.3
k_mL21a = 21.0
k_mL21g = 4.3
k_mL21k = 0.22
k_mL21p = 0.4
k_mL2f = 0.57
k_mL2r = 1.4
k_mL3f = 0.01
k_mL3r = 0.0034
k_mL4 = 0.18
k_mL5f = 0.03
k_mL5r = 0.8
k_mL6 = 0.22
k_mL7 = 0.0204
k_p1 = 0.5
k_p2 = 2.0
k_s1f = 0.0
k_s1r = 0.0
k_s2 = 0.02
k_s3f = 0.01
k_s3r = 0.01
k_s4f = 0.07
k_s4r = 0.0
k_tF1 = 0.01
k_tF3 = 0.008
k_tL1 = 100.0
k_tL2 = 0.1
k_tL3 = 0.1
k_tL5 = 0.1
k_tL6 = 1.0
k_tS1 = 0.01
k_tS2 = 1.0
k_tS3 = 0.01
k_tS4 = 3.0
kc1 = 1.0
kcm1 = 4e-08
kcm2 = 1e-06
kd_Balan = 0.015
kd_Bffa = 0.015
kd_Bgluc = 0.015
kd_Bglucgn = 0.015
kd_Bins = 0.015
kd_Bket = 0.015
kd_Blac = 0.015
kf = 0.5
kg2 = 0.5
kg3 = 1200.0
kg4 = 300.0
kg5 = 1200.0
kg6 = 300.0
kg7 = 1200.0
kg8 = 300.0
kgi = 10.0
kmg3 = 0.0004
kmg4 = 0.0011
kmg5 = 0.01
kmg6 = 0.005
kmg7 = 0.015
kmg8 = 0.00012
kresume = 0.6
ks_dket = 0.01
kt = 0.0025
ng = 10.0
ni = 10.0
p1 = 1.0
p2 = 1.0
pt = 0.07
s1 = 100.0
s2 = 0.001
st = 0.003
tresume = 20250.0
F_ffa = 2
M_alan = 0.4
PKb = 0.0025
blood = 1.0
fat = 1.0
glycogen_regulation = 1.0
liver = 1.0
muscle = 1.0


#initial values
B_alan = 0.1
B_ffa = 0.3
B_gluc = 4
B_glucgn = 0
B_ins = 0
B_ket = 0.08
B_lac = 0.2
Cvar = 0
F_TG = 0
F_acyl = 0
F_g6p = 0
GPa = 0.035
GSa = 0.0015
M_g6p = 8
M_glycgn = 100
M_ket = 0.1
M_lac = 0.2
M_pyr = 0.2
PKa = 0
PP1 = 0.00025
PP1_GPa = 0
R2C2 = 0.00025
R2_C_cAMP2 = 0
R2_cAMP4 = 0
aK = 1
acet_c = 6
acet_m = 7
alan = 0.1
cAMP = 0
citrate = 0.5
g6p = 0.2
gluc = 5
glutamate = 0.1
glycgn = 10
ket = 0.08
lac = 1
malate = 3
malonyl = 0.3
oa_c = 0.0004
oa_m = 0.0002
palm = 0.3
palmCoA = 0.3
pep = 0.001
pyr = 3


#assignment rules
!F k1ins = kd_Bins * (Imax - Imin)
!F kgc1 = k_gc1 / k11
!F kgc2 = k_gc2 / k22
!F kmg5s = kmg5 * (1 + s1 * g6p / kg2)
!F kmg6s = kmg6 / (1 + s2 * gluc / kgi)
!F kmg7s = kmg7 * (1 + s1 * g6p / kg2)
!F kmg8s = kmg8 / (1 + s1 * g6p / kg2)
!F kc2 = kc1 * pow(10, 5.5)
!F ka = k_a / kd
!F k_glucgn = kd_Bglucgn * Gmax
!F k1glucgn = kd_Bglucgn * (Gmax - Gmin)
!F kd = (cmax - cmin) * pow(c0, index) / (pow(c0, index) + pow(glycgn, index)) + cmin
!F k_ins = kd_Bins * Imin
!F GPaPlot = GPa/0.07
!F GSaPlot = GSa/0.003