Microarray-sequencing of WT and Jam3-null leukemia-initiating cells (LICs)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE109311 | GEO | 2018/01/18
SECONDARY ACCESSION(S): PRJNA430404
REPOSITORIES: GEO
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Project description:Microarray-sequencing of WT and Jam3-null leukemia-initiating cells (LICs)
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Project description: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
SBO:0000290 physical compartment
GO:0005739 mitochondrion
mm
mitochondrial membrane
2
Y
SBO:0000290 physical compartment
GO:0031966 mitochondrial membrane
pm
plasma membrane
2
Y
SBO:0000290 physical compartment
GO:0005886 plasma membrane
Species
Id
Name
Compartment
Constant
Init [mM]
KEGG
CHEBI
UNIPROT
SBO
atp
ATP
cyto
Y
2.8
KEGG:C00002
CHEBI:15422
SBO:0000299 metabolite
adp
ADP
cyto
Y
0.8
KEGG:C00008
CHEBI:16761
SBO:0000299 metabolite
amp
AMP
cyto
Y
0.16
KEGG:C00020
CHEBI:16027
SBO:0000299 metabolite
utp
UTP
cyto
N
0.27
KEGG:C00075
CHEBI:15713
SBO:0000299 metabolite
udp
UDP
cyto
N
0.09
KEGG:C00015
CHEBI:17659
SBO:0000299 metabolite
gtp
GTP
cyto
N
0.29
KEGG:C00044
CHEBI:15996
SBO:0000299 metabolite
gdp
GDP
cyto
N
0.10
KEGG:C00035
CHEBI:17552
SBO:0000299 metabolite
nad
NAD+
cyto
Y
1.22
KEGG:C00003
CHEBI:15846
SBO:0000299 metabolite
nadh
NADH
cyto
Y
5.60E-004
KEGG:C00004
CHEBI:16908
SBO:0000299 metabolite
p
phosphate
cyto
Y
5
KEGG:C00009
SBO:0000299 metabolite
pp
pyrophosphate
cyto
N
0.008
KEGG:C00013
SBO:0000299 metabolite
h2o
H2O
cyto
Y
55000
KEGG:C00001
CHEBI:15377
SBO:0000299 metabolite
co2
CO2
cyto
Y
5
KEGG:C00011
CHEBI:16526
SBO:0000299 metabolite
h
H+
cyto
Y
5.00E-008
KEGG:C00080
CHEBI:24636
SBO:0000299 metabolite
glc1p
glucose-1-phosphate
cyto
N
0.012
KEGG:C00103
CHEBI:16077
SBO:0000299 metabolite
udpglc
UDP-glucose
cyto
N
0.38
KEGG:C00029
CHEBI:18066
SBO:0000299 metabolite
glc
glucose
cyto
N
5
KEGG:C00031
CHEBI:4167
SBO:0000299 metabolite
glyglc
glycogen
cyto
N
250
KEGG:C00182
CHEBI:28087
SBO:0000299 metabolite
fru6p
fructose-6-phosphate
cyto
N
0.05
KEGG:C00085
CHEBI:15946
SBO:0000299 metabolite
glc6p
glucose-6-phosphate
cyto
N
0.12
KEGG:C00092
CHEBI:4170
SBO:0000299 metabolite
fru26bp
fructose-2,6-bisphospate
cyto
N
0.004
KEGG:C00665
CHEBI:28602
SBO:0000299 metabolite
fru16bp
fructose-1,6-bisphospate
cyto
N
0.02
KEGG:C00354
CHEBI:16905
SBO:0000299 metabolite
dhap
dihydroxyacetone phosphate
cyto
N
0.03
KEGG:C00111
CHEBI:16108
SBO:0000299 metabolite
grap
glyceraldehyde 3-phosphate
cyto
N
0.1
KEGG:C00118
CHEBI:29052
SBO:0000299 metabolite
pg3
3-phosphoglycerate
cyto
N
0.27
KEGG:C00197
CHEBI:17794
SBO:0000299 metabolite
bpg13
1,3-bisphospho-glycerate
cyto
N
0.3
KEGG:C00236
CHEBI:16001
SBO:0000299 metabolite
pep
phosphoenolpyruvate
cyto
N
0.15
KEGG:C00074
CHEBI:44897
SBO:0000299 metabolite
pg2
2-phosphoglycerate
cyto
N
0.03
KEGG:C00631
CHEBI:17835
SBO:0000299 metabolite
oaa
oxaloacetate
cyto
N
0.01
KEGG:C00036
CHEBI:30744
SBO:0000299 metabolite
pyr
pyruvate
cyto
N
0.1
KEGG:C00022
CHEBI:32816
SBO:0000299 metabolite
glc_blood
glucose
blood
Y
5
KEGG:C00031
CHEBI:4167
SBO:0000299 metabolite
lac
lactate
cyto
N
0.5
KEGG:C00186
CHEBI:422
SBO:0000299 metabolite
p_mito
phosphate
mito
Y
5
KEGG:C00009
SBO:0000299 metabolite
oaa_mito
oxaloacetate
mito
N
0.01
KEGG:C00036
CHEBI:30744
SBO:0000299 metabolite
lac_blood
lactate
blood
Y
1.2
KEGG:C00186
CHEBI:422
SBO:0000299 metabolite
co2_mito
CO2
mito
Y
5
KEGG:C00011
CHEBI:16526
SBO:0000299 metabolite
pyr_mito
pyruvate
mito
N
0.1
KEGG:C00022
CHEBI:32816
SBO:0000299 metabolite
cit_mito
citrate
mito
Y
0.32
KEGG:C00158
CHEBI:30769
SBO:0000299 metabolite
pep_mito
pep
mito
N
0.15
KEGG:C00074
CHEBI:44897
SBO:0000299 metabolite
acoa_mito
acetyl-coenzyme A
mito
Y
0.04
KEGG:C00024
CHEBI:15351
SBO:0000299 metabolite
gtp_mito
GTP
mito
N
0.29
KEGG:C00044
CHEBI:15996
SBO:0000299 metabolite
gdp_mito
GDP
mito
N
0.10
KEGG:C00035
CHEBI:17552
SBO:0000299 metabolite
atp_mito
ATP
mito
Y
2.8
KEGG:C00002
CHEBI:15422
SBO:0000299 metabolite
adp_mito
ADP
mito
Y
0.8
KEGG:C00008
CHEBI:16761
SBO:0000299 metabolite
nad_mito
NAD+
mito
Y
0.98
KEGG:C00003
CHEBI:15846
SBO:0000299 metabolite
h_mito
H+
mito
Y
1.00E-008
KEGG:C00011
CHEBI:24636
SBO:0000299 metabolite
coa_mito
coenzymeA
mito
Y
0.055
KEGG:C00010
CHEBI:15346
SBO:0000299 metabolite
nadh_mito
NADH
mito
Y
0.24
KEGG:C00004
CHEBI:16908
SBO:0000299 metabolite
epinephrine_blood
epinephrine
blood
N
206.11
KEGG:C00547
CHEBI:18357
SBO:0000299 metabolite
glucagon_blood
glucagon
blood
N
4.36E-008
KEGG:C01501
UNIPROT:P01275
SBO:0000299 metabolite
insulin_blood
insulin
blood
N
7.61E-008
KEGG:C00723
UNIPROT:P01308
SBO:0000299 metabolite
h20_mito
H2O
mito
Y
55000
KEGG:C00080
CHEBI:15377
SBO:0000299 metabolite
Reactions
Id
Name
Compartment
Irreversible
Vmax [µmol/kg/min]
EC
KEGG
UNIPROT
SBO
GLUT2
GLUT2 glucose transporter (facilitated diffusion)
pm
N
420
UNIPROT:P11168
SBO:0000284 transporter
GK
Glucokinase, hexokinase IV
cyto
Y
25.2
EC:2.7.1.2
KEGG:R00299
UNIPROT:P35557
SBO:0000014 enzyme
G6PASE
Glucose-6-phosphatase
cyto
Y
18.9
EC:3.1.3.9
KEGG:R00303
UNIPROT:P35575
SBO:0000014 enzyme
GPI
Glucose-6-phosphate isomerase
cyto
N
420
EC:5.3.1.9
KEGG:R00771
UNIPROT:P06744
SBO:0000014 enzyme
G16PI
glucose-1-phosphate 1,6-phosphomutase
cyto
N
100
EC:5.4.2.2
KEGG:R00959
UNIPROT:P36871, UNIPROT:Q96G03
SBO:0000014 enzyme
UPGASE
UTP:Glucose-1-phosphate uridylyltransferase
cyto
N
80
EC:2.7.7.9
KEGG:R00289
UNIPROT:Q16851
SBO:0000014 enzyme
PPASE
Pyrophosphate phosphohydrolase
cyto
Y
2.4
EC:3.6.1.1
KEGG:R00004
UNIPROT:Q15181
SBO:0000014 enzyme
GS
Glycogen synthase
cyto
Y
13.2
UNIPROT:P54840
SBO:0000014 enzyme
GP
Glycogen phosphorylase
cyto
N
6.8
UNIPROT:P06737
SBO:0000014 enzyme
NTKGTP
Nucleosid diphosphate kinase (GTP)
cyto
N
0
EC:2.7.4.6
KEGG:R00330
SBO:0000014 enzyme
NTKUTP
Nucleosid diphosphate kinase (UTP)
cyto
N
2940
EC:2.7.4.6
KEGG:R00156
SBO:0000014 enzyme
AK
Adenylat kinase
cyto
N
0
EC:2.7.4.3
KEGG:R00127
SBO:0000014 enzyme
PFK2
Phosphofructo kinase 2
cyto
Y
0.0042
EC:2.7.1.105
KEGG:R02732
UNIPROT:P16118
SBO:0000014 enzyme
FBP2
Fructose-2,6-bisphosphatase
cyto
Y
0.126
EC:3.1.3.46
KEGG:R02731
UNIPROT:P16118
SBO:0000014 enzyme
PFK1
Phosphofructo kinase 1
cyto
Y
7.182
EC:2.7.1.11
KEGG:R00756
UNIPROT:P17858
SBO:0000014 enzyme
FBP1
Fructose-1,6-bisphosphatase
cyto
Y
4.326
EC:3.1.3.11
KEGG:R00762
UNIPROT:O00757, UNIPROT:P09467
SBO:0000014 enzyme
TPI
Triosephosphate isomerase
cyto
N
420
EC:5.3.1.1
KEGG:R01015
UNIPROT:P60174
SBO:0000014 enzyme
ALD
Aldolase
cyto
N
420
EC:4.1.2.13
KEGG:R01068
UNIPROT:P05062
SBO:0000014 enzyme
PGK
Phosphoglycerate kinase
cyto
N
420
EC:2.7.2.3
KEGG:R01512
UNIPROT:P00558
SBO:0000014 enzyme
GAPDH
Glyceraldehydephosphate dehydrogenase
cyto
N
420
EC:1.2.1.12
KEGG:R01061
UNIPROT:P04406
SBO:0000014 enzyme
EN
Enolase
cyto
N
35.994
EC:4.2.1.11
KEGG:R00658
UNIPROT:P06733, UNIPROT:P09104, UNIPROT:P13929
SBO:0000014 enzyme
PGAM
3-Phosphoglycerate mutase
cyto
N
420
EC:5.4.2.1
KEGG:R01518
UNIPROT:P18669
SBO:0000014 enzyme
PEPCK
Phosphoenolpyruvate carboxykinase
cyto
N
0
EC:4.1.1.32
KEGG:R00431
UNIPROT:P35558
SBO:0000014 enzyme
PK
Pyruvate kinase
cyto
Y
46.2
EC:2.7.1.40
KEGG:R00200
UNIPROT:P30613
SBO:0000014 enzyme
PC
Pyruvate Carboxylase
mito
Y
168
EC:6.4.1.1
KEGG:R00344
UNIPROT:P11498
SBO:0000014 enzyme
PEPCK_mito
Phosphoenolpyruvate carboxykinase
mito
N
546
EC:4.1.1.32
KEGG:R00431
UNIPROT:Q16822
SBO:0000014 enzyme
LACT
Lactate transporter
pm
N
5.418
SBO:0000284 transporter
LDH
Lactate dehydrogenase
cyto
N
12.6
EC:1.1.1.27
-KEGG:R00703
UNIPROT:P00338, UNIPROT:P07195, UNIPROT:P07864
SBO:0000014 enzyme
PEPT
PEP transporter
mm
N
33.6
SBO:0000284 transporter
PYRT
Pyruvate transporter
mm
N
42
SBO:0000284 transporter
CS
Citrate synthase
mito
N
4.2
EC:2.3.3.1
-KEGG:R00351
UNIPROT:O75390
SBO:0000014 enzyme
PDH
Pyruvate dehydrogenase
mito
Y
13.44
EC:1.2.4.1
KEGG:R00209
UNIPROT:P08559, UNIPROT:P11177, UNIPROT:P10515, UNIPROT:P09622, O00330
SBO:0000014 enzyme
ACOAFLX
Acetyl-CoA flux
mito
N
0
SBO:0000014 enzyme
VCITFLX
Citrate flux
mito
N
0
SBO:0000014 enzyme
NDK_mito
Nucleosid diphosphate kinase (GTP)
mito
N
420
EC:2.7.4.6
KEGG:R00330
SBO:0000014 enzyme
OAAFLX
Oxalacetate flux
mito
N
0
SBO:0000014 enzyme
2005-01-01 | MODEL1204270001 | BioModels