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

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Homo sapiens


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
6.4.1.1
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RECOMMENDED NAME
GeneOntology No.
pyruvate carboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxylation
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-
-
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cleavage of C-N-linkage
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hydrolysis of peptide bond
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
gluconeogenesis II (Methanobacterium thermoautotrophicum)
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gluconeogenesis III
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incomplete reductive TCA cycle
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Methanobacterium thermoautotrophicum biosynthetic metabolism
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anapleurotic synthesis of oxalacetate
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Citrate cycle (TCA cycle)
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Pyruvate metabolism
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Carbon fixation pathways in prokaryotes
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Metabolic pathways
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Microbial metabolism in diverse environments
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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
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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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
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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
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
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pyruvate carboxylase deficiency in humans causes severe acidosis
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ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
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-
-
-
?
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
?
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enzyme deficiency is a rare autosomal recessive disease
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-
NATURAL SUBSTRATES
NATURAL PRODUCTS
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
?
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enzyme deficiency is a rare autosomal recessive disease
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-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
biotin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
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the carboxytransferase domain contains a tightly bound Mn2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-aspartate
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allosteric inhibitor
TNFalpha
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pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
biotin
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TNFalpha
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pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
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additional information
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starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
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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
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nondiabetic subjects
47.8
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type 2 diabetic patients
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
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assay at
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
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SDS-PAGE
127370
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x * 127370, calculation from nucleotide sequence
130000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
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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
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modeling of three-dimensional structure
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminal region from Escherichia coli strain BL21(DE3)
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recombinant enzyme and enzyme from liver
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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
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expressed in 293T cells
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expressed in L-929 cells
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expression in type B pyruvate decarboxylase deficient skin fibroblasts
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expression of the C-terminal region, excluding the mitochondrial targeting sequence, in Escherichia coli strain BL21(DE3)
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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
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genetic structure, expression analysis, genotyping of genetic variants
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F1077A
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mutant cyrstal structure, overview
M743I
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naturally occurring mutation involved in pyruvate carboxylase deficiency type A
R451C
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naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant enzyme shows markedly decreased acetyl-CoA-dependent activation
V145A
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naturally occurring mutation involved in pyruvate carboxylase deficiency type A
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
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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