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Information on EC 6.4.1.1 - pyruvate carboxylase and Organism(s) Rattus norvegicus and UniProt Accession P52873
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6.4.1.1 pyruvate carboxylaseIUBMB Comments
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
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Word Map
- 6.4.1.1
- phosphoenolpyruvate
-
gluconeogenesis
-
carboxykinase
- biotin
- oxaloacetate
- acetyl-coa
-
tricarboxylic
-
gluconeogenic
-
anaplerotic
- malate
- citrate
- tca
- co2
-
malic
- pepck
- carboxylases
- astrocyte
- glucose-6-phosphatase
-
biotin-dependent
- acidosis
- propionyl-coa
-
citric
-
krebs
- glutamicum
-
bark
- pine
-
biotin-containing
-
13c-labeled
-
propionyl
-
isotopomer
-
maritime
-
1-13cglucose
- avidin
- hyperammonemia
-
fructose-1,6-diphosphatase
- carboxyltransferase
-
pyrogenic
-
4.1.1.32
-
1,6-bisphosphatase
- holocarboxylase
- transcarboxylase
- biotinidase
-
pyrolytic
- leigh
-
ureagenesis
- medicine
-
glucogenic
- biotechnology
- penicillinase
-
13c-enriched
- pinaster
- synthesis
- 3-methylcrotonyl-coa
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
pyruvate carboxylase, pyc, pcase, hppyc1p, pyc1p, pyruvate carboxylase 1, ehpyc1, pyruvic carboxylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Carboxylase, pyruvate
-
-
-
-
PCB
-
-
-
-
Pyruvic carboxylase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
pyruvate:carbon-dioxide ligase (ADP-forming)
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
CAS REGISTRY NUMBER
COMMENTARY
9014-19-1
-
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
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
pyruvate carboxylase, and thereby anaplerosis, is crucial for an appropriate rise in the ATP:ADP ratio in response to fuel metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the enzyme is involved in mitochondrial metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
ATP in form of MgATP2-
-
-
?
additional information
?
-
beta-cells possess compensatory systems that are activated in response to suppression of pyruvate carboxylase nzyme levels. The compensatory events include allosteric activation of pyruvate carboxylase due to increased levels of acetyl-CoA and enhanced conversion of isocitrate to 2-oxoglutarate and downstream metabolites via the cytosolic, NADP-dependent isocitrate dehydrogenase
-
-
?
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase rats
-
-
?
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
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
pyruvate carboxylase, and thereby anaplerosis, is crucial for an appropriate rise in the ATP:ADP ratio in response to fuel metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the enzyme is involved in mitochondrial metabolism
-
-
?
additional information
?
-
beta-cells possess compensatory systems that are activated in response to suppression of pyruvate carboxylase nzyme levels. The compensatory events include allosteric activation of pyruvate carboxylase due to increased levels of acetyl-CoA and enhanced conversion of isocitrate to 2-oxoglutarate and downstream metabolites via the cytosolic, NADP-dependent isocitrate dehydrogenase
-
-
?
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase rats
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
acetyl-CoA
-
in absence of acetyl-CoA the maximal rate of oxaloacetate synthesis is 21% of that observed in the presence of saturating concentrations of the activator
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9.3
-
7.0: about 65% of maximal activity, 9.3: about 35% of maximal activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
enzyme activity is preserved in the islets of obese animals, but it is reduced in the islets of animal models of type 2 diabetes
additional information
-
tissue-specific expression, production of specific forms of PC mRNA are linked to certain physiological states, i.e. development, gluconeogenesis and lipogenesis
beta-cells possess compensatory systems that are activated in response to suppression of pyruvate carboxylase nzyme levels. The compensatory events include allosteric activation of pyruvate carboxylase due to increased levels of acetyl-CoA and enhanced conversion of isocitrate to 2-oxoglutarate and downstream metabolites via the cytosolic, NADP-dependent isocitrate dehydrogenase
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). PYC_RAT
1178
0
129777
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
additional information
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
suppression by stable expression of siRNA causes impaired anaplerosis and insulin secretion in insulinoma cells, knockout in INS-1 832/13 cells, cell lines U6 and CHS, and in INS-1 832/13-derived cell lines PCX3, PC1971, PC1973, PC3064, and PC118. Insulin release in response to pyruvate alone, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid plus glutamine, or methyl succinate plus beta-hydroxybutyrate is also decreased in the PC knockdown cells, phenotype, overview
additional information
-
overexpression of v-MAFA in INS1 cells causes a 5fold increase of pyruvate carboxylase mRNA
additional information
-
stable overexpression of the enzyme in INS-1 cells leads to significantly upregulated insulin secretion and cell proliferation, while enzyme downregulation by siRNA expression reduces insulin secretion and cell proliferation, phenotypes, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dilution results in irreversible inactivation, which can be partially avoided by addition of acetyl-CoA. Glycerol stabilizes
-
inactivated reversibly and converted to protomers by incubation at 0°C in the presence of high concentrations of Cl- salts of monovalent cations. MgCl2 or sucrose prevent inactivation
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression analysis of the enzyme in diverse wild-type and knockout insulinoma cell lines, overview
DNA and amino acid sequence determination and analysis, genetic structure, key cognate transcription factors regulating tissue-specific expression. Five species of enzyme mRNAs have been reported, each having the same coding sequence but differing in their 5'-untranslated regions. These mRNA variants are the product of alternative splicing of two primary transcripts initiated from two alternative promoters, the proximal and the distal promoters. Neither of these promoters contains a TATA box but both possess multiple GC boxes. Production of specific forms of PC mRNA are linked to certain physiological states, i.e. development, gluconeogenesis and lipogenesis. Two pancreatic isletspecific transcription factors, i.e. pancreatic duodenal homeobox-1or PDX1, and v-MAFA, are involved in transcriptional regulation of the enzyme in INS1 cells. Identification of a putative cAMP-responsive element in the proximal promoter of the rat PC gene, transcriptional regulation, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of pyruvate carboxylase is be increased 2-5fold at the onset of obesity in Zucker fatty rats
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ahmad, F.; Ahmad, P.M.; Mendez, A.
Rat liver pyruvate carboxylase. Purification, detection and quantification of apo and holo forms by immuno-blotting and by an enzyme-linked immunosorbent assay
Biochem. J.
236
527-533
1986
Homo sapiens, Mammalia, Rattus norvegicus
Libor, S.M.; Sundaram, T.K.; Scrutton, M.C.
Pyruvate carboxylase from a thermophilic Bacillus
Biochem. J.
169
543-558
1978
Bacillus sp. (in: Bacteria), Saccharomyces cerevisiae, Gallus gallus, Rattus norvegicus
Rowan, A.N.; Newsholme, E.A.; Scrutton, M.C.
Partial purification and some properties of pyruvate carboxylase from the flight muscle of the locust Schistocerca gregaria
Biochim. Biophys. Acta
522
270-275
1978
Schistocerca gregaria, Rattus norvegicus, Tenebrio molitor
Barden, R.E.; Taylor, B.L.; Isohashi, F.; Frey, W.H.; Zander, G.; Lee, J.C.; Utter, M.F.
Structural properties of pyruvate carboxylase from chicken liver and other sources
Proc. Natl. Acad. Sci. USA
72
4308-4312
1975
Bos taurus, Saccharomyces cerevisiae, Gallus gallus, Homo sapiens, Meleagris gallopavo, Pseudomonas citronellolis, Rattus norvegicus, Sus scrofa
Mahan, D.E.; Mushahwar, I.K.; Koeppe, R.E.
Purification and properties of rat brain pyruvate carboxylase
Biochem. J.
145
25-35
1975
Rattus norvegicus
Nakashima, K.; Rudolph, F.B.; Wakabayashi, T.; Lardy, H.A.
Rat liver pyruvate carboxylase. V. Reversible dissociation by chloride salts of monovalent cations
J. Biol. Chem.
250
331-336
1975
Rattus norvegicus
Scrutton, M.C.; White, M.D.
Pyruvate carboxylase from rat liver: catalytic properties in the absence, and at low concentrations, of acetyl-CoA
Biochem. Biophys. Res. Commun.
48
85-93
1972
Rattus norvegicus
Thampy, K.G.; Huang, W.Y.; Wakil, S.J.
A rapid purification method for rat liver pyruvate carboxylase and amino acid sequence analyses of NH2-terminal and biotin peptide
Arch. Biochem. Biophys.
266
270-276
1988
Rattus norvegicus
Griffith, A.D.; Cyr, D.M.; Egan, S.G.; Tremblay, G.C.
Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate
Arch. Biochem. Biophys.
269
201-207
1989
Rattus norvegicus
Salto, R.; Lahoz, J.M.; del Mar Sola, M.; Oliver, J.; Vargas, A.M.
Purification and characterization of pyruvate carboxylase from rat-kidney cortex
Biochem. Arch.
6
385-395
1990
Rattus norvegicus
-
Liu, Y.Q.; Jetton, T.L.; Leahy, J.L.
beta-Cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats
J. Biol. Chem.
277
39163-39168
2002
Rattus norvegicus
Fransson, U.; Rosengren, A.H.; Schuit, F.C.; Renstroem, E.; Mulder, H.
Anaplerosis via pyruvate carboxylase is required for the fuel-induced rise in the ATP:ADP ratio in rat pancreatic islets
Diabetologia
49
1578-1586
2006
Rattus norvegicus
Jensen, M.V.; Joseph, J.W.; Ilkayeva, O.; Burgess, S.; Lu, D.; Ronnebaum, S.M.; Odegaard, M.; Becker, T.C.; Sherry, A.D.; Newgard, C.B.
Compensatory responses to pyruvate carboxylase suppression in islet beta-cells. Preservation of glucose-stimulated insulin secretion
J. Biol. Chem.
281
22342-22351
2006
Rattus norvegicus (P52873)
Jitrapakdee, S.; St Maurice, M.; Rayment, I.; Cleland, W.W.; Wallace, J.C.; Attwood, P.V.
Structure, mechanism and regulation of pyruvate carboxylase
Biochem. J.
413
369-387
2008
Aquifex aeolicus, Geobacillus thermodenitrificans, Bos taurus, Saccharomyces cerevisiae, Ogataea angusta, Homo sapiens, Methanobacterium sp., Methanococcus sp., Methanosarcina sp., Staphylococcus aureus, Mus musculus, Komagataella pastoris, Pseudomonas sp., Rattus norvegicus, Rhizobium etli
Xu, J.; Han, J.; Long, Y.S.; Epstein, P.N.; Liu, Y.Q.
The role of pyruvate carboxylase in insulin secretion and proliferation in rat pancreatic beta cells
Diabetologia
51
2022-2030
2008
Rattus norvegicus
Hasan, N.M.; Longacre, M.J.; Stoker, S.W.; Boonsaen, T.; Jitrapakdee, S.; Kendrick, M.A.; Wallace, J.C.; MacDonald, M.J.
Impaired anaplerosis and insulin secretion in insulinoma cells caused by small interfering RNA-mediated suppression of pyruvate carboxylase
J. Biol. Chem.
283
28048-28059
2008
Rattus norvegicus (P52873)
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