836317
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168255
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837038
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167595
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167235
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836965
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name: PFK2

168603
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168219
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167823
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168543
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168087
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836485
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168567
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836137
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836869
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836905
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836557
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168303
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836893
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168591
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837050
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167223
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167175
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167523
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837001
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168195
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836293
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168003
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836617
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836641
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836977
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167535
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167439
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167811
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836329
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168267
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836581
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167247
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167583
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168579
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167331
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167895
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167991
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168099
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836149
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is: SBO:0000290
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size: 10000.0
spatial dimensions: 3.0
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type: Compartment

836857
product: 167211
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168555
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836497
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836881
type: Reaction
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name: UPGASE
is: R00289
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836569
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initial concentration: 0.5
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boundary condition: false

168315
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836341
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836917
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836653
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name: pep_mito

836281
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836629
initial concentration: 0.1
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in compartment: 836161
is: SBO:0000299
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type: Species

167271
is: SBO:0000011
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species: 836317
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836197
name: atp
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constant: false
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is: C00002
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substance units: 167043
boundary condition: false

167187
is: SBO:0000011
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167211
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species: 836413
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168291
is: SBO:0000011
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species: 836569
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837013
name: ALD
fast: false
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product: 167751
is: P05062
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reversible: true
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type: Reaction
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168327
is: SBO:0000011
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168483
is: SBO:0000015
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species: 836809
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167343
is: SBO:0000011
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species: 836245
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168111
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species: 836653
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167739
is: SBO:0000011
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species: 836473
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837122
is: R00344
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fast: false
product: 168231
is: P11498
reversible: false
is: SBO:0000014
reactant: 168183
name: PC
product: 168219
reactant: 168171
type: Reaction
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167079
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species: 836557
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167259
is: SBO:0000015
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species: 836365
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168279
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167931
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167751
is: SBO:0000011
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species: 836461
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836941
reversible: true
is: SBO:0000014
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product: 167487
type: Reaction
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name: NTKUTP
is: R00156
fast: false
product: 167475

836461
has only substance units: false
constant: false
substance units: 167043
is: SBO:0000299
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boundary condition: false
initial amount: NaN
is: C00111
initial concentration: 0.03
name: dhap

167847
is: SBO:0000011
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species: 836497
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836209
initial concentration: 0.8
boundary condition: false
substance units: 167043
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name: adp
initial amount: NaN
is: C00008
is: SBO:0000299
constant: false
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type: Species

167427
is: SBO:0000011
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species: 836209
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167667
is: SBO:0000011
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species: 836449
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837025
product: 167775
reactant: 167763
is: P60174
is: R01015
is: SBO:0000014
fast: false
reversible: true
name: TPI
type: Reaction

837074
product: 167943
reversible: true
is: P09104
is: R00658
type: Reaction
product: 167955
is: P13929
reactant: 167931
fast: false
name: EN
is: P06733
is: SBO:0000014

167379
is: SBO:0000015
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species: 836401
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836665
type: Species
is: C00024
substance units: 167043
boundary condition: false
name: acoa_mito
initial amount: NaN
constant: false
is: SBO:0000299
initial concentration: 0.04
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has only substance units: false

167151
is: SBO:0000015
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species: 836329
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168027
is: SBO:0000015
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species: 836533
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168171
is: SBO:0000015
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species: 836617
type: SpeciesReference

836353
constant: false
is: C00080
initial concentration: 5.0E-8
type: Species
has only substance units: false
name: h
in compartment: 836137
substance units: 167043
boundary condition: false
initial amount: NaN
is: SBO:0000299

168507
is: SBO:0000011
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species: 836749
type: SpeciesReference

836413
is: SBO:0000299
boundary condition: false
name: fru6p
initial amount: NaN
is: C00085
constant: false
type: Species
substance units: 167043
in compartment: 836137
has only substance units: false
initial concentration: 0.05

836377
is: SBO:0000299
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substance units: 167043
type: Species
initial concentration: 0.38
in compartment: 836137
name: udpglc
is: C00029
boundary condition: false
initial amount: NaN
constant: false

836713
name: adp_mito
is: SBO:0000299
initial amount: NaN
has only substance units: false
type: Species
is: C00008
boundary condition: false
in compartment: 836161
substance units: 167043
initial concentration: 0.8
constant: false

168495
is: SBO:0000011
stoichiometry: 1.0
species: 836641
type: SpeciesReference

837110
product: 168159
product: 168135
fast: false
name: PEPCK_mito
reversible: true
product: 168099
reactant: 168075
type: Reaction
is: Q16822
is: R00431
reactant: 168087
product: 168147
is: SBO:0000014
product: 168123
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168399
is: SBO:0000015
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species: 836725
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167355
is: SBO:0000011
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species: 836401
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836929
product: 167427
reversible: true
reactant: 167403
is: R00330
is: SBO:0000014
reactant: 167415
fast: false
type: Reaction
name: NTKGTP
product: 167439

168339
product: 168363
reactant: 168351
is: SBO:0000284
fast: false
reversible: true
name: PYRT
type: Reaction

168531
is: SBO:0000015
stoichiometry: 1.0
species: 836689
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836473
substance units: 167043
has only substance units: false
is: C00118
initial concentration: 0.1
initial amount: NaN
type: Species
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boundary condition: false
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is: SBO:0000299

167415
is: SBO:0000015
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species: 836269
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167835
is: SBO:0000011
stoichiometry: 1.0
species: 836353
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167727
is: SBO:0000015
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species: 836449
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836305
name: p
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type: Species
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substance units: 167043
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in compartment: 836137
is: SBO:0000299
boundary condition: false

167067
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

836953
product: 167523
reactant: 167511
reactant: 167499
is: R00127
is: SBO:0000014
fast: false
reversible: true
name: AK
type: Reaction

836605
boundary condition: false
initial amount: NaN
is: SBO:0000299
is: C00186
initial concentration: 1.2
substance units: 167043
constant: false
name: lac_blood
in compartment: 836149
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has only substance units: false

168015
is: SBO:0000015
stoichiometry: 1.0
species: 836257
type: SpeciesReference

836677
initial amount: NaN
name: gtp_mito
constant: false
is: SBO:0000299
type: Species
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in compartment: 836161
has only substance units: false
substance units: 167043
initial concentration: 0.29
boundary condition: false

167163
is: SBO:0000015
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species: 836425
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168183
is: SBO:0000015
stoichiometry: 1.0
species: 836629
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167367
is: SBO:0000015
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species: 836305
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837062
product: 167919
reactant: 167907
is: P18669
is: R01518
is: SBO:0000014
fast: false
reversible: true
name: PGAM
type: Reaction

167691
is: SBO:0000015
stoichiometry: 1.0
species: 836449
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167511
is: SBO:0000015
stoichiometry: 1.0
species: 836221
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836761
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constant: false
is: C00004
boundary condition: false
name: nadh_mito
substance units: 167043
has only substance units: false
type: Species
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initial concentration: 0.24
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836509
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type: Species
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constant: false
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initial concentration: 0.15
is: C00074
substance units: 167043
has only substance units: false

836389
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boundary condition: false
substance units: 167043
name: glc
in compartment: 836137
type: Species
initial concentration: 5.0
initial amount: NaN
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is: SBO:0000299
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836701
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initial amount: NaN
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type: Species
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initial concentration: 2.8
is: C00002
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substance units: 167043
constant: false
name: atp_mito

836365
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has only substance units: false
initial amount: NaN
is: SBO:0000299
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constant: false
substance units: 167043
boundary condition: false
is: C00103
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836401
substance units: 167043
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has only substance units: false
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type: Species
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boundary condition: false
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constant: false
name: glyglc

168519
is: SBO:0000015
stoichiometry: 1.0
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168435
is: SBO:0000011
stoichiometry: 1.0
species: 836761
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836425
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has only substance units: false
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substance units: 167043
constant: false
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836521
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is: C00631
substance units: 167043
type: Species
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initial amount: NaN
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836749
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836773
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boundary condition: false
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type: Species
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is: SBO:0000299
name: epinephrine_blood
substance units: 167043

167679
is: SBO:0000015
stoichiometry: 1.0
species: 836329
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167451
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stoichiometry: 1.0
species: 836197
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836833
is: SBO:0000014
reversible: false
product: 167139
reactant: 167103
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is: P35557
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type: Reaction
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is: R00299
name: GK

167775
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stoichiometry: 1.0
species: 836473
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167955
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168123
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167655
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168075
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167103
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167043
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type: SBMLUnitsDef

837134
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fast: false
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reactant: 168255
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168375
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168423
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167307
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species: 836329
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MODEL1204270001
species: 836689
reaction: 168339
species: 836533
species: 836617
length unit: length
species: 836317
species: 836737
species: 836461
species: 836425
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reaction: 837038
reaction: 836929
species: 836785
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species: 836521
reaction: 168303
time units: 291235
species: 836305
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reaction: 837074
species: 836569
reaction: 837158
species: 836545
species: 836281
species: 836329
reaction: 836965
species: 836245
compartment: 836137
is described by: http://identifiers.org/pubmed/22761565
area units: 061696
reaction: 836977
compartment: 836149
reaction: 837001
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species: 836665
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notes: Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism Kinetic Model of Human Hepatic Glucose Metabolism Authors Matthias Koenig, Sascha Bulik and Hermann-Georg Holzhuetter Corresponding Author Matthias Koenig matthias.koenig@charite.de Charite Berlin, Computational Systems Biochemistry, Germany Keywords hepatic glucose metabolism; kinetic model; glucose homeostasis; liver Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present, a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in excellent agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from hepatic glucose production under hypoglycemia to hepatic glucose utilization under hyperglycemia essential for glucose homeostasis. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. Compartments Id Name Dimension Constant SBO GO cyto cytosol 3 Y SBO:0000290 physical compartment GO:0005829 cytosol blood blood 3 Y SBO:0000290 physical compartment GO:0005615 extracellular space mito mitochondrion 3 Y S…
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