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MODEL1204270001 - Koenig2012_HepaticGlucoseMetabolism

 

The following model is part of the non-curated branch of BioModels Database. While the syntax of the model has been verified, its semantics remains unchecked. Any annotation present in the models is not a product of BioModels' annotators. We are doing our best to incorporate this model into the curated branch as soon as possible. In the meantime, we display only limited metadata here. For further information about the model, please download the SBML file.


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Reference Publication
Publication ID: 22761565
König M, Bulik S, Holzhütter HG.
Quantifying the contribution of the liver to glucose homeostasis: a detailed kinetic model of human hepatic glucose metabolism.
PLoS Comput. Biol. 2012; 8(6): e1002577
Institute of Biochemistry, University Medicine Charité Berlin, Berlin, Germany. matthias.koenig@charite.de  [more]
Model
Original Model: MODEL1204270001.origin
Submitter: Matthias König
Submission Date: 27 Apr 2012 11:56:59 UTC
Last Modification Date: 04 Dec 2012 18:42:35 UTC
Creation Date: 10 May 2012 17:30:30 UTC
Encoders:
bqbiol:isVersionOf Gene Ontology glucose homeostasis
Human Disease Ontology diabetes mellitus
bqbiol:hasTaxon Taxonomy Homo sapiens
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 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

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