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Information on EC 4.1.1.32 - phosphoenolpyruvate carboxykinase (GTP) and Organism(s) Homo sapiens and UniProt Accession P35558
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4.1.1.32 phosphoenolpyruvate carboxykinase (GTP)IUBMB Comments
ITP can act as phosphate donor.
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Word Map
- 4.1.1.32
- biliary
- cirrhosis
-
gluconeogenesis
- autoantigens
- autoimmune
-
gluconeogenic
- autoantibody
- epitope
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lipoylated
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antimitochondrial
- camp
- glucocorticoid
- bile
-
immunodominant
- malate
-
malic
-
autoreactive
- cholangitis
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intrahepatic
-
lipoic
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autoepitope
-
glyceroneogenesis
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dibutyryl
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6.4.1.1
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anaplerotic
-
3-mercaptopicolinic
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2.7.1.40
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bt2camp
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pbc-specific
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fto-2b
- oxalacetate
- 2-oxo-acid
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ama-positive
- dihydrolipoamide
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self-tolerance
- drug development
- synthesis
- pharmacology
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
pdc-e2, pepck-c, pep carboxykinase, p-enolpyruvate carboxykinase, phosphoenolpyruvate carboxykinase (gtp), pepck-m, pep-carboxykinase, phosphopyruvate carboxylase, phosphopyruvate carboxykinase, gtp:oxaloacetate carboxy-lyase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
carboxykinase, phosphopyruvate (guanosine triphosphate)
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-
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oxaloacetate kinase (decarboxylating, GDP)
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-
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P-enolpyruvate carboxykinase
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PEP carboxykinase
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-
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PEP carboxylase
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PEPCK
PEPCK-C
phosphoenolpyruvate carboxykinase
Phosphoenolpyruvate carboxylase
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phosphoenolpyruvate carboxylase (GTP)
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phosphoenolpyruvic carboxykinase
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phosphoenolpyruvic carboxykinase (GTP)
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phosphoenolpyruvic carboxykinase (inosine triphosphate)
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Phosphoenolpyruvic carboxylase
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-
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phosphoenolpyruvic carboxylase (GTP)
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-
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phosphoenolpyruvic carboxylase (inosine triphosphate)
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-
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phosphopyruvate carboxykinase
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-
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phosphopyruvate carboxylase
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phosphopyruvate carboxylase (GTP)
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-
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PEPCK
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phosphoenolpyruvate carboxykinase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylation
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-
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decarboxylation
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-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -
SYSTEMATIC NAME
IUBMB Comments
GTP:oxaloacetate carboxy-lyase (adding GTP; phosphoenolpyruvate-forming)
ITP can act as phosphate donor.
CAS REGISTRY NUMBER
COMMENTARY
9013-08-5
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
GTP-dependent, enzyme and GTP-binding site structure
phosphoenolpyruvate binds as a 1:1 complex with Na+, structure of the phosphoenolpyruvate-binding site
r
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
catalyzes the rate-limiting step in gluconeogenesis
-
?
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
catalyzes the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle
-
?
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
key enzyme of gluconeogenesis, involved in lipid homeostasis
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
catalyzes the rate-limiting step in gluconeogenesis
-
?
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
catalyzes the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle
-
?
GTP + oxaloacetate
GDP + phosphoenolpyruvate + CO2
-
key enzyme of gluconeogenesis, involved in lipid homeostasis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
the IC50 values for Mn2+ are 0.009 mM for Mg2+ concentration 2 mM, wild-type, Vmax = 31 micromol/min/mg, 0.607 mM for Mg2+ concentration 2 mM, Y235F mutant, Vmax = 4 micromol/min/mg, 0.073 mM for Mg2+ concentration 2 mM, Y235A mutant, Vmax = 19 micromol/min/mg, 0.058 mM for Mg2+ concentration 2 mM, Y235S mutant, Vmax = 13 micromol/min/mg, 0.0008 mM for wild-type, Vmax = 29 micromol/min/mg, 0.0007 mM for Y235F mutant, Vmax = 31 micromol/min/mg, 0.0004 mM for Y235A mutant, Vmax = 2 micromol/min/mg, 0.0007 mM for Y235S mutant, Vmax = 2 micromol/min/mg, 0.009 mM for wild-type, Mg2+ concentration 5 mM, Vmax = 31 micromol/min/mg, 0.562 mM for Y235F mutant, Mg2+ concentration 5 mM, Vmax = 4 micromol/min/mg, 0.064 mM for Y235A mutant, Mg2+ concentration 5 mM, Vmax = 18 micromol/min/mg, 0.048 mM for Y235S mutant, Mg2+ concentration 5 mM, Vmax = 13 micromol/min/mg, 0.009 mM for wild-type, Mg2+ concentration 7.5 mM, Vmax = 31 micromol/min/mg, 0.521 mM for Y235F mutant, Mg2+ concentration 7.5 mM, Vmax = 4 micromol/min/mg, 0.057 mM for Y235A mutant, Mg2+ concentration 7.5 mM, Vmax = 18 micromol/min/mg, 0.043 mM for Y235S mutant, Mg2+ concentration 7.5 mM, Vmax = 13 micromol/min/mg
Mn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-allyl-3-butyl-8-methylxanthine
-
weak, competitive inhibitor with respect to GTP, IC50: 0.225 mM in the decarboxylation direction, modifications at N-1 and C-8 improve the inhibitory activity by more than 100fold
3-Mercaptopicolinic acid
-
reversible, non-competitive inhibitor, IC50: in the 0.02 mM range
additional information
-
study of several modified 3-alkyl-1,8-dibenzylxanthines as competitive inhibitors with respect to GTP, IC50-values
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
all-trans-retinoic acid is a transcriptional inducer of the PEPCK-C gene. 9-cis-retinoic acid and all-trans-retinoic acid stimulate PEPCK-C expression in 3T3-442A adipocytes
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additional information
-
all-trans-retinoic acid is a transcriptional inducer of the PEPCK-C gene. 9-cis-retinoic acid and all-trans-retinoic acid stimulate PEPCK-C expression in 3T3-442A adipocytes
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additional information
-
PEPCK mRNA expression in the subcutaneous adipose tissues is associated with body mass index and plasma triacylglycerol and total cholesterol levels, but is not correlated with insulin resistance index
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20.6
GDP
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in 100 mM HEPES-NaOH, pH 8, 3.6 mM L-malate, 10 mM dithiothreitol, 2 mM MgCl2, 0.2 mM MnCl2, at 37°C
0.023
GTP
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in 100 mM HEPES-NaOH, pH 7.2, 100 mM KHCO3, 10 mM dithiothreitol, 2 mM MgCl2, 0.2 mM MnCl2, at 37°C
0.004
oxaloacetate
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in 100 mM HEPES-NaOH, pH 7.2, 100 mM KHCO3, 10 mM dithiothreitol, 2 mM MgCl2, 0.2 mM MnCl2, at 37°C
0.45
phosphoenolpyruvate
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in 100 mM HEPES-NaOH, pH 8, 3.6 mM L-malate, 10 mM dithiothreitol, 2 mM MgCl2, 0.2 mM MnCl2, at 37°C
0.034
GDP
Mg2+ concentration 2 mM, Y235A mutant. Vmax = 15 micromol/min/mg
0.034
GDP
Mg2+ concentration 7.5 mM, Y235A mutant. Vmax = 15 micromol/min/mg
0.035
GDP
Mg2+ concentration 5 mM, Y235A mutant. Vmax = 15 micromol/min/mg
0.04
GDP
Mg2+ concentration 5 mM, Y235S mutant. Vmax = 10 micromol/min/mg
0.041
GDP
Mg2+ concentration 7.5 mM, wild-type. Vmax = 35 micromol/min/mg
0.044
GDP
Mg2+ concentration 2 mM, Y235S mutant. Vmax = 11 micromol/min/mg
0.047
GDP
Mg2+ concentration 2 mM, Y235F mutant. Vmax = 3 micromol/min/mg
0.053
GDP
Mg2+ concentration 7.5 mM, Y235S mutant. Vmax = 11 micromol/min/mg
0.067
GDP
Mg2+ concentration 7.5 mM, Y235F mutant. Vmax = 3 micromol/min/mg
0.036
phosphoenolpyruvate
Mn2+ concentration 1.5 mM, Mg2+ concentration 2 mM, Y235F mutant. Vmax = 3 micromol/min/mg
0.217
phosphoenolpyruvate
Mn2+ concentration 1.5 mM, Mg2+ concentration 2 mM, wild-type. Vmax = 31 micromol/min/mg
0.919
phosphoenolpyruvate
Mn2+ concentration 1.5 mM, Mg2+ concentration 2 mM, Y235A mutant. Vmax = 20 micromol/min/mg
1.256
phosphoenolpyruvate
Mn2+ concentration 1.5 mM, Mg2+ concentration 2 mM, Y235S mutant. Vmax = 15 micromol/min/mg
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.225
1-allyl-3-butyl-8-methylxanthine
Homo sapiens
-
weak, competitive inhibitor with respect to GTP, IC50: 0.225 mM in the decarboxylation direction, modifications at N-1 and C-8 improve the inhibitory activity by more than 100fold
0.02
3-Mercaptopicolinic acid
Homo sapiens
-
reversible, non-competitive inhibitor, IC50: in the 0.02 mM range
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
women, aged 45.7 +/- 4.4 years and have body mass index of 30.3 +/- 1.4 kg m-2
UniProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PCKGC_HUMAN
622
0
69195
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme alone and in complexes with the non-hydrolyzable GTP analog beta,gamma-methylene GTP, and with phosphoenolpyruvate, hanging-drop vapor-diffusion method, X-ray analysis
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA Superflow agarose column chromatography and Ekapture-agarose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
activation of SIRT1 by resveratrol represses transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) by deacetylating hepatic nuclear factor 4alpha. Isonicotinamide decreases the level of mRNA for PEPCK-C with an IC50 of 2.3 mM
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pharmacology
synthesis
heterlogous expression in the Escherichia coli dcuD mutant improves hydrogen and ethanol synthesis when grown in a glycerol-based medium. Hydrogen and ethanol specific productions and glycerol consumption increase by 2.46, 1.73 and 1.95 times, respectively, upon the expression
medicine
-
inhibitors of PEPCK may be useful in the treatment of type II diabetes
pharmacology
-
development of a PEPCK inhibitor may lead to a new therapeutic strategy for the treatment of type II diabetes
pharmacology
-
orally active compounds reversibly inhibiting PEPCK improve glucose homeostasis in type 2 diabetics
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ting, C.N.; Burgess, D.L.; Chamberlain, J.S.; Keith, T.P.; Falls, K.; Meisler, M.H.
Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20
Genomics
16
698-706
1993
Homo sapiens
Foley, L.H.; Wang, P.; Dunten, P.; Ramsey, G.; Gubler, M.L.; Wertheimer, S.J.
Modified 3-alkyl-1,8-dibenzylxanthines as GTP-competitive inhibitors of phosphoenolpyruvate carboxykinase
Bioorg. Med. Chem. Lett.
13
3607-3610
2003
Homo sapiens
Dunten, P.; Belunis, C.; Crowther, R.; Hollfelder, K.; Kammlott, U.; Levin, W.; Michel, H.; Ramsey, G.B.; Swain, A.; Weber, D.; Wertheimer, S.J.
Crystal structure of human cytosolic phosphoenolpyruvate carboxykinase reveals a new GTP-binding site
J. Mol. Biol.
316
257-264
2002
Homo sapiens
Cadoudal, T.; Leroyer, S.; Reis, A.F.; Tordjman, J.; Durant, S.; Fouque, F.; Collinet, M.; Quette, J.; Chauvet, G.; Beale, E.; Velho, G.; Antoine, B.; Benelli, C.; Forest, C.
Proposed involvement of adipocyte glyceroneogenesis and phosphoenolpyruvate carboxykinase in the metabolic syndrome
Biochimie
87
27-32
2005
Homo sapiens
Case, C.L.; Mukhopadhyay, B.
Kinetic characterization of recombinant human cytosolic phosphoenolpyruvate carboxykinase with and without a His10-tag
Biochim. Biophys. Acta
1770
1576-1584
2007
Homo sapiens
Beale, E.G.; Harvey, B.J.; Forest, C.
PCK1 and PCK2 as candidate diabetes and obesity genes
Cell Biochem. Biophys.
48
89-95
2007
Homo sapiens, Mus musculus
Dharmarajan, L.; Case, C.L.; Dunten, P.; Mukhopadhyay, B.
Tyr235 of human cytosolic phosphoenolpyruvate carboxykinase influences catalysis through an anion-quadrupole interaction with phosphoenolpyruvate carboxylate
FEBS J.
275
5810-5819
2008
Homo sapiens (P35558)
Cadoudal, T.; Glorian, M.; Massias, A.; Fouque, F.; Forest, C.; Benelli, C.
Retinoids upregulate phosphoenolpyruvate carboxykinase and glyceroneogenesis in human and rodent adipocytes
J. Nutr.
138
1004-1009
2008
Rattus norvegicus, Homo sapiens (P35558), Homo sapiens
Chang, T.J.; Lee, W.J.; Chang, H.M.; Lee, K.C.; Chuang, L.M.
Expression of subcutaneous adipose tissue phosphoenolpyruvate carboxykinase correlates with body mass index in nondiabetic women
Metab. Clin. Exp.
57
367-372
2008
Homo sapiens
Yang, J.; Kong, X.; Martins-Santos, M.E.; Aleman, G.; Chaco, E.; Liu, G.E.; Wu, S.Y.; Samols, D.; Hakimi, P.; Chiang, C.M.; Hanson, R.W.
Activation of SIRT1 by resveratrol represses transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) by deacetylating hepatic nuclear factor 4alpha
J. Biol. Chem.
284
27042-27053
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Valle, A.; Cabrera, G.; Cantero, D.; Bolivar, J.
Heterologous expression of the human phosphoenol pyruvate carboxykinase (hPEPCK-M) improves hydrogen and ethanol synthesis in the Escherichia coli dcuD mutant when grown in a glycerol-based medium
New Biotechnol.
35
1-12
2017
Homo sapiens (Q16822), Homo sapiens
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