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Information on EC 6.4.1.1 - pyruvate carboxylase and Organism(s) Homo sapiens

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IUBMB Comments
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
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This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
pyruvate carboxylase, pyc, pcase, hppyc1p, pyruvate carboxylase 1, pyc1p, pyruvic carboxylase, ehpyc1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Carboxylase, pyruvate
-
-
-
-
PCB
-
-
-
-
Pyruvic carboxylase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxylation
-
-
-
-
cleavage of C-N-linkage
hydrolysis of peptide bond
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 hide
9014-19-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
pyruvate carboxylase deficiency in humans causes severe acidosis
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme deficiency is a rare autosomal recessive disease
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
pyruvate carboxylase deficiency in humans causes severe acidosis
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
additional information
?
-
-
enzyme deficiency is a rare autosomal recessive disease
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
biotin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
the carboxytransferase domain contains a tightly bound Mn2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-aspartate
-
allosteric inhibitor
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
biotin
-
-
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
additional information
-
starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22 - 0.25
ATP
1.75 - 3.2
HCO3-
0.08 - 0.23
pyruvate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43.8
-
nondiabetic subjects
47.8
-
type 2 diabetic patients
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
pyruvate decarboxylase deficiency type A is characterised by hypoglycemia accompanied by mild to moderate lactic acidemia and sometimes elevated ketone body levels. Type B, having no detectable pyruvate carboxylase protein in any tissues, is the most severe form which leads to death generally within three months from lactic academia accompanied by hyperammonemia, citrullinemia and hyperlysinemia. Type C has a benign phenotype associated with episodes of lactic acidemia and no psychomotor disorders
physiological function
-
pyruvate carboxylase (PC) is required for glutamine-independent growth of tumor cells. PC-mediated, glucose-dependent anaplerosis allows cells to achieve glutamine independence. PC is required for cell growth during glutamine deprivation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PYC_HUMAN
1178
0
129634
Swiss-Prot
Mitochondrion (Reliability: 2)
A0A024R5C5_HUMAN
1178
0
129634
TrEMBL
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
SDS-PAGE
127370
-
x * 127370, calculation from nucleotide sequence
130000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
-
-
tetramer
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
C-terminal region, and wild-type and F1077A mutant enzymes, microseeding, room temprarture, sitting drop method using a reservoir solution containing 0.8% w/v PEG 3350 and 90 mM MnCl for the wild-type and 15% w/v PEG 3350 and 200 mM ammonium tartrate for the mutant, X-ray diffraction structure determination and analysis at 2.8 A resolution
modeling of three-dimensional structure
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A610T
F1077A
mutant cyrstal structure, overview
M743I
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
R451C
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant enzyme shows markedly decreased acetyl-CoA-dependent activation
V145A
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminal region from Escherichia coli strain BL21(DE3)
recombinant enzyme and enzyme from liver
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, genetic structure, key cognate transcription factors regulating tissue-specific expression, transcriptional regulation, overview
-
expressed in 293T cells
expressed in L-929 cells
-
expression in type B pyruvate decarboxylase deficient skin fibroblasts
-
expression of the C-terminal region, excluding the mitochondrial targeting sequence, in Escherichia coli strain BL21(DE3)
FLAG-tagged human pyruvate carboxylase is introduced into a dihydrofolate-deficient CHO cell line DG44. Through the expression of the human pyruvate carboxylase enzyme, lactate formation in CHO cell culture can be efficiently reduced. This effect of expression of the human pyruvate carboxylase is observed not only in adherent batch culture using the serum-containing medium but in the serum-free suspension fed-batch culture as well, demonstrating its potential use to extend the culture longevity of CHO cell culture, which often shows a significant accumulation of lactate
genetic structure, expression analysis, genotyping of genetic variants
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
FLAG-tagged human pyruvate carboxylase is introduced into a dihydrofolate-deficient CHO cell line DG44. Through the expression of the human pyruvate carboxylase enzyme, lactate formation in CHO cell culture can be efficiently reduced. This effect of expression of the human pyruvate carboxylase is observed not only in adherent batch culture using the serum-containing medium but in the serum-free suspension fed-batch culture as well, demonstrating its potential use to extend the culture longevity of CHO cell culture, which often shows a significant accumulation of lactate
medicine
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
MacKay, N.; Rigat, B.; Douglas, C.; Chen, H.S.; Robinson, B.H.
cDNA cloning of human kidney pyruvate carboxylase
Biochem. Biophys. Res. Commun.
29
1009-1014
1994
Homo sapiens
Manually annotated by BRENDA team
Wexler, I.D.; Du, Y.; Lisgaris, M.V.; Mandal, S.K.; Freytag, S.O.; Yang, B.S.; Liu, T.C.; Kwon, M.; Patel, M.S.; Kerr, D.S.
Primary amino acid sequence and structure of human pyruvate carboxylase
Biochim. Biophys. Acta
1227
46-52
1994
Homo sapiens
Manually annotated by BRENDA team
Chandler, C.S.; Ballard, F.J.
Distribution and degradation of biotin-containing carboxylases in human cell lines
Biochem. J.
232
385-393
1985
Homo sapiens
Manually annotated by BRENDA team
Jitrapakdee, S.; Walker, M.E.; Wallace, J.C.
Functional expression, purification, and characterization of recombinant human pyruvate carboxylase
Biochem. Biophys. Res. Commun.
266
512-517
1999
Homo sapiens (P11498), Homo sapiens
Manually annotated by BRENDA team
Jitrapakdee, S.; Wallace, J.C.
Structure, function and regulation of pyruvate carboxylase
Biochem. J.
340
1-16
1999
Geobacillus stearothermophilus, Saccharomyces cerevisiae, Mammalia, Methanothermobacter thermautotrophicus, Rhizobium etli, Homo sapiens (P11498)
-
Manually annotated by BRENDA team
Carbone, M.A.; Robinson, B.H.
Expression and characterization of a human pyruvate carboxylase variant by retroviral gene transfer
Biochem. J.
370
275-282
2003
Homo sapiens
Manually annotated by BRENDA team
Kim, Y.H.; Kim, S.S.
Bcl-2 inhibits tumor necrosis factor-alpha-mediated increase of glycolytic enzyme activities and enhances pyruvate carboxylase activity
Mol. Cells
16
67-73
2003
Homo sapiens
Manually annotated by BRENDA team
Baez-Saldana, A.; Zendejas-Ruiz, I.; Revilla-Monsalve, C.; Islas-Andrade, S.; Cardenas, A.; Rojas-Ochoa, A.; Vilches, A.; Fernandez-Mejia, C.
Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects
Am. J. Clin. Nutr.
79
238-243
2004
Homo sapiens
Manually annotated by BRENDA team
Vlasova, T.I.; Stratton, S.L.; Wells, A.M.; Mock, N.I.; Mock, D.M.
Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood
J. Nutr.
135
42-47
2005
Homo sapiens
Manually annotated by BRENDA team
Kim, S.H.; Lee, G.M.
Functional expression of human pyruvate carboxylase for reduced lactic acid formation of Chinese hamster ovary cells (DG44)
Appl. Microbiol. Biotechnol.
76
659-665
2007
Homo sapiens (P11498), Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Wang, D.; Yang, H.; De Braganca, K.C.; Lu, J.; Yu Shih, L.; Briones, P.; Lang, T.; De Vivo, D.C.
The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival
Mol. Genet. Metab.
95
31-38
2008
Homo sapiens
Manually annotated by BRENDA team
Xiang, S.; Tong, L.
Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction
Nat. Struct. Mol. Biol.
15
295-302
2008
Staphylococcus aureus (A0A0H3JRU9), Staphylococcus aureus, Homo sapiens (P11498), Homo sapiens
Manually annotated by BRENDA team
Monnot, S.; Serre, V.; Chadefaux-Vekemans, B.; Aupetit, J.; Romano, S.; De Lonlay, P.; Rival, J.M.; Munnich, A.; Steffann, J.; Bonnefont, J.P.
Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency
Hum. Mutat.
30
734-740
2009
Homo sapiens
Manually annotated by BRENDA team
Fan, T.W.; Lane, A.N.; Higashi, R.M.; Farag, M.A.; Gao, H.; Bousamra, M.; Miller, D.M.
Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM)
Mol. Cancer
8
41
2009
Homo sapiens
Manually annotated by BRENDA team
Minet, A.D.; Gaster, M.
Pyruvate carboxylase is expressed in human skeletal muscle
Biochem. Biophys. Res. Commun.
402
196-197
2010
Homo sapiens
Manually annotated by BRENDA team
Wallace, J.
My favorite pyruvate carboxylase
IUBMB Life
62
535-538
2010
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Cheng, T.; Sudderth, J.; Yang, C.; Mullen, A.; Jin, E.; Mates, J.; DeBerardinis, R.
Pyruvate carboxylase is required for glutamine-independent growth of tumor cells
Proc. Natl. Acad. Sci. USA
108
8674-8679
2011
Homo sapiens
Manually annotated by BRENDA team
Sellers, K.; Fox, M.P.; Bousamra, M.; Slone, S.P.; Higashi, R.M.; Miller, D.M.; Wang, Y.; Yan, J.; Yuneva, M.O.; Deshpande, R.; Lane, A.N.; Fan, T.W.
Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation
J. Clin. Invest.
125
687-698
2015
Homo sapiens (P11498), Homo sapiens
Manually annotated by BRENDA team
Phannasil, P.; Thuwajit, C.; Warnnissorn, M.; Wallace, J.; MacDonald, M.; Jitrapakdee, S.
Pyruvate carboxylase is up-regulated in breast cancer and essential to support growth and invasion of MDA-MB-231 cells
PLoS ONE
10
e0129848
2015
Homo sapiens (P11498), Homo sapiens
Manually annotated by BRENDA team