Information on EC 6.4.1.1 - pyruvate carboxylase

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

EC NUMBER
COMMENTARY
6.4.1.1
-
RECOMMENDED NAME
GeneOntology No.
pyruvate carboxylase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
mechanism, overview
-
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
reaction mechanism of ATP cleavage and biotin carboxylation, overview
-
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
catalytic mechanism involves the decarboxylation of carboxybiotin and removal of a proton from Thr882 by the resulting biotin enolate with either a concerted or subsequent transfer of a proton from pyruvate to Thr882. The resulting enolpyruvate then reacts with CO2 to form oxaloacetate and complete the reaction
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
carboxylation
-
-
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-, O17732
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
Ogataea angusta ass3, Sinorhizobium meliloti Rm1021
-
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-, O17732
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
Ogataea angusta ass3, Sinorhizobium meliloti Rm1021
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Carbon fixation pathways in prokaryotes
-
Citrate cycle (TCA cycle)
-
gluconeogenesis II (Methanobacterium thermoautotrophicum)
-
gluconeogenesis III
-
incomplete reductive TCA cycle
-
itaconate biosynthesis
-
Metabolic pathways
-
Methanobacterium thermoautotrophicum biosynthetic metabolism
-
Microbial metabolism in diverse environments
-
Pyruvate metabolism
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Carboxylase, pyruvate
-
-
-
-
HpPyc1p
-
-
HpPyc1p
Ogataea angusta ass3
-
-
-
Pcase
-
-
PCB
-
-
-
-
PYC
Listeria monocytogenes Sv1/2a EGD-e
-
-
-
PYC
Pseudomonas aeruginosa P4
-
-
-
Pyc1
Saccharomyces cerevisiae DM18
P11154
-
-
PYC2
Saccharomyces cerevisiae DM18
P32327
-
-
pycA
-
gene name
pycA
Listeria monocytogenes Sv1/2a EGD-e
-
gene name
-
pyruvate carboxylase
-
-
pyruvate carboxylase
Pseudomonas aeruginosa P4
-
-
-
pyruvate carboxylase
-
-
pyruvate carboxylase
-
-
pyruvate carboxylase 1
P11154
-
Pyruvic carboxylase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9014-19-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
thermophilic
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
lung cancer patients
-
-
Manually annotated by BRENDA team
Leptosphaeria michotii
-
-
-
Manually annotated by BRENDA team
Listeria monocytogenes Sv1/2a EGD-e
-
-
-
Manually annotated by BRENDA team
Methanococcus sp.
-
-
-
Manually annotated by BRENDA team
type 2 diabetic Agouti-K mice
-
-
Manually annotated by BRENDA team
Ogataea angusta ass3
ass3
-
-
Manually annotated by BRENDA team
strain ATCC 17933
-
-
Manually annotated by BRENDA team
strain P4 (soil-isolate)
-
-
Manually annotated by BRENDA team
strain PAO1
-
-
Manually annotated by BRENDA team
wild-type strain PAO1, genes pycA and pycB ecoding pyruvate carboxylase subunits PycA and PycB
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa P4
strain P4 (soil-isolate)
-
-
Manually annotated by BRENDA team
strain ATCC 13525
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Zucker fatty and Zucker lean rats
-
-
Manually annotated by BRENDA team
overexpressing strain
-
-
Manually annotated by BRENDA team
two isozymes PYC1 and PYC2
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae DM18
strain DM18
SwissProt
Manually annotated by BRENDA team
Sinorhizobium meliloti Rm1021
Rm1021
-
-
Manually annotated by BRENDA team
Thiobacillus sp. A2
A2
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
malfunction
-
a pycA insertion mutant defective in pyruvate carboxylase still grows, albeit at a reduced rate, in brain heart infusion medium but is unable to multiply in a defined minimal medium with glucose or glycerol as a carbon source. The mutant is also unable to replicate in mammalian cells and exhibits high virulence attenuation in the mouse sepsis model
malfunction
Listeria monocytogenes Sv1/2a EGD-e
-
a pycA insertion mutant defective in pyruvate carboxylase still grows, albeit at a reduced rate, in brain heart infusion medium but is unable to multiply in a defined minimal medium with glucose or glycerol as a carbon source. The mutant is also unable to replicate in mammalian cells and exhibits high virulence attenuation in the mouse sepsis model
-
metabolism
-
the PYC-catalyzed carboxylation of pyruvate is the predominant reaction leading to oxaloacetate in Listeria monocytogenes
metabolism
Listeria monocytogenes Sv1/2a EGD-e
-
the PYC-catalyzed carboxylation of pyruvate is the predominant reaction leading to oxaloacetate in Listeria monocytogenes
-
physiological function
-
pyruvate carboxylase protein is required for import and assembly of the peroxisomal enzyme alcohol oxidase
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + carbamoyl phosphate
ATP + ?
show the reaction diagram
-
-
-
-
ADP + carbamoyl phosphate
ATP + ?
show the reaction diagram
-
-
-
?
ADP + carbamoyl phosphate
ATP + ?
show the reaction diagram
-
-
-
?
ADP + carbamoyl phosphate
ATP + ?
show the reaction diagram
-
at 0.3% of the rate obtained from pyruvate-carboxylation
-
-
-
ATP + oxamate + HCO3- + H+
ADP + phosphate + ?
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
P11498
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Leptosphaeria michotii
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-, O17732
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Q99UY8
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Q29RK2
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
intact enzyme and PC-(BC) chain are able to cleave ATP in the presence of free D-biotin and absence of pyruvate
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
anaplerotic enzyme
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
anaplerotic enzyme for growth on carbohydrates, reaction is a major bottleneck for amino acid production
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
cells containing the enzyme yield significantly more cell mass while generating less acetate
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
essential for normal growth
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
role in gluconeogenesis, lipogenesis, biosynthesis of neurotransmitter substances and in glucose-induced insulin secretion by pancreatic islets
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
role of anaplerosis in the central carbon metabolism and amino acid synthesis
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
P11154, P32327
Pyc1 and Pyc2 display different allosteric properties with respect to acetyl CoA activation and aspartate inhibition, with Pyc1 showing a higher degree of cooperativity than Pyc2, even in the absence of aspartate
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
show the reaction diagram
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
show the reaction diagram
Q29RK2
the enzyme catalyzes a pivotal reaction in gluconeogenesis and lipid metabolism in liver, and is a regulatory enzyme in gluconeogenesis that catalyzes the biotin-dependent carboxylation of pyruvate to form oxaloacetate
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Q99UY8
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, and other cellular processes
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme is involved in mitochondrial metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme plays a pivotal role in intermediary metabolism. It serves a critical anaplerotic function replenishing the Krebs cycle intermediates by catalyzing the conversion of pyruvate to oxaloacetate. In addition, pyruvate carboxylase controls the first step of hepatic gluconeogenesis, and is involved in lipogenesis
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the overall catalysis by PC proceeds in two steps. First, the biotin carboxylase domain catalyzes the carboxylation of biotin, which is covalently linked to the biotin carboxylaseCP. Bicarbonate donates the carboxyl group, and ATP is hydrolyzed to ADP in this reaction. The carboxytransferase domain then catalyzes the transfer of the activated carboxyl group to pyruvate to produce the oxaloacetate product
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Thiobacillus sp. A2
-
-
-
-
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Ogataea angusta ass3
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Sinorhizobium meliloti Rm1021
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Saccharomyces cerevisiae DM18
P11154, P32327
Pyc1 and Pyc2 display different allosteric properties with respect to acetyl CoA activation and aspartate inhibition, with Pyc1 showing a higher degree of cooperativity than Pyc2, even in the absence of aspartate
-
-
?
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
meets anaplerotic and/or biosynthetic needs in metabolism
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
the enzyme occupies a strategic position in the intermediary metabolism of numerous tissues. In the gluconeogenic tissues, e.g. liver, kidney, it catalyzes the first step in the synthesis of glucose from pyruvate. During lipogenesis in liver, adipose tissue and mammary gland it participates in the synthesis of acetyl groups and reducing groups for transport from the mitochondria to the cytosol. In yet other tissues it fulfills an anaplerotic function
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
anaplerotic CO2 fixation
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
anaplerotic CO2 fixation
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
enzyme synthesis is induced by pyruvate and repressed by tricarboxylic acid cycle intermediates
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
enzyme is necessary for growth in minimal medium with pyruvate as sole carbon source
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
Leptosphaeria michotii
-
one of the enzymes of the asparagine-pyruvate pathway
-
-
-
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 + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
involvement of several ionisable residues in both ATP-cleavage and biotin carboxylation
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
Pseudomonas aeruginosa P4
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
r
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
r
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
Listeria monocytogenes, Listeria monocytogenes Sv1/2a EGD-e
-
-
-
-
?
additional information
?
-
-
HCO3--dependent ATP cleavage catalyzed in absence of pyruvate
-
-
-
additional information
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
additional information
?
-
P52873
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
?
-
-
the transcarboxylase domain of pyruvate carboxylase is essential for assembly of the peroxisomal flavoenzyme alcohol oxidase
-
-
-
additional information
?
-
-
enzyme deficiency is a rare autosomal recessive disease
-
-
-
additional information
?
-
-
in yeast, two metabolic pathways leading to the production of oxaloacetate are the pyruvate carboxylase-catalysed reaction and the glyoxylate cycle.When yeast is grown on acetate, pyruvate carboxylase-catalysed oxaloacetate formation is repressed but the glyoxylate cycle is active, and vice versa if grown on glucose minimal medium
-
-
-
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase mice
-
-
-
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
-
-
-
additional information
?
-
-
the enzyme is regulated by a pyruvate carboxylase regulator, encoded by gene PA5437 or pycR, PycR inactivation results in 100 000fold attenuation of virulence in the rat lung in vivo, PycR is a regulator with pleiotropic effects on virulence factors, such as lipase and esterase expression and biofilm formation, which are important for maintenance of Pseudomonas aeruginosa in chronic lung infection, overview
-
-
-
additional information
?
-
-
ATP cleavage by the recombinantly expressed isolated biotin carboxylase domain, overview
-
-
-
additional information
?
-
-
the enzyme in adipocytes interacts with prohibitin, a protein involved in mitochondrial biogenesis
-
-
-
additional information
?
-
-
the enzyme interacts with the biotin protein ligase or holocarboxylase, EC 6.3.4.15, and is associated with the peroxisomal alcohol oxidase
-
-
-
additional information
?
-
-
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate is no substrate
-
-
-
additional information
?
-
Ogataea angusta ass3
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
P11498
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-, O17732
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
anaplerotic enzyme
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
anaplerotic enzyme for growth on carbohydrates, reaction is a major bottleneck for amino acid production
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
cells containing the enzyme yield significantly more cell mass while generating less acetate
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
essential for normal growth
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
role in gluconeogenesis, lipogenesis, biosynthesis of neurotransmitter substances and in glucose-induced insulin secretion by pancreatic islets
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
role of anaplerosis in the central carbon metabolism and amino acid synthesis
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
P11154, P32327
Pyc1 and Pyc2 display different allosteric properties with respect to acetyl CoA activation and aspartate inhibition, with Pyc1 showing a higher degree of cooperativity than Pyc2, even in the absence of aspartate
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
show the reaction diagram
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
show the reaction diagram
Q29RK2
the enzyme catalyzes a pivotal reaction in gluconeogenesis and lipid metabolism in liver, and is a regulatory enzyme in gluconeogenesis that catalyzes the biotin-dependent carboxylation of pyruvate to form oxaloacetate
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Q99UY8
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, and other cellular processes
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme is involved in mitochondrial metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the enzyme plays a pivotal role in intermediary metabolism. It serves a critical anaplerotic function replenishing the Krebs cycle intermediates by catalyzing the conversion of pyruvate to oxaloacetate. In addition, pyruvate carboxylase controls the first step of hepatic gluconeogenesis, and is involved in lipogenesis
-
-
?
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
meets anaplerotic and/or biosynthetic needs in metabolism
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
the enzyme occupies a strategic position in the intermediary metabolism of numerous tissues. In the gluconeogenic tissues, e.g. liver, kidney, it catalyzes the first step in the synthesis of glucose from pyruvate. During lipogenesis in liver, adipose tissue and mammary gland it participates in the synthesis of acetyl groups and reducing groups for transport from the mitochondria to the cytosol. In yet other tissues it fulfills an anaplerotic function
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
anaplerotic CO2 fixation
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
anaplerotic CO2 fixation
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
enzyme synthesis is induced by pyruvate and repressed by tricarboxylic acid cycle intermediates
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
-
enzyme is necessary for growth in minimal medium with pyruvate as sole carbon source
-
-
-
ATP + pyruvate + HCO3-
?
show the reaction diagram
Leptosphaeria michotii
-
one of the enzymes of the asparagine-pyruvate pathway
-
-
-
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 + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Sinorhizobium meliloti Rm1021
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
Saccharomyces cerevisiae DM18
P11154, P32327
Pyc1 and Pyc2 display different allosteric properties with respect to acetyl CoA activation and aspartate inhibition, with Pyc1 showing a higher degree of cooperativity than Pyc2, even in the absence of aspartate
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
-
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
-
-
?
additional information
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
additional information
?
-
P52873
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
?
-
-
the transcarboxylase domain of pyruvate carboxylase is essential for assembly of the peroxisomal flavoenzyme alcohol oxidase
-
-
-
additional information
?
-
-
enzyme deficiency is a rare autosomal recessive disease
-
-
-
additional information
?
-
-
in yeast, two metabolic pathways leading to the production of oxaloacetate are the pyruvate carboxylase-catalysed reaction and the glyoxylate cycle.When yeast is grown on acetate, pyruvate carboxylase-catalysed oxaloacetate formation is repressed but the glyoxylate cycle is active, and vice versa if grown on glucose minimal medium
-
-
-
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase mice
-
-
-
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
-
-
-
additional information
?
-
-
the enzyme is regulated by a pyruvate carboxylase regulator, encoded by gene PA5437 or pycR, PycR inactivation results in 100 000fold attenuation of virulence in the rat lung in vivo, PycR is a regulator with pleiotropic effects on virulence factors, such as lipase and esterase expression and biofilm formation, which are important for maintenance of Pseudomonas aeruginosa in chronic lung infection, overview
-
-
-
additional information
?
-
Ogataea angusta ass3
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
-
at concentrations above saturating, MgATP2- activates bicarbonate-dependent ATP cleavage, but inhibits the overall reaction
biotin
-
enzyme contains biotin; enzyme contains covalently bound D-biotin
biotin
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
Leptosphaeria michotii
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
-
enzyme contains biotin
biotin
-
activity is dependent on biotin availability
biotin
-
dependent, enzyme contains biotin
biotin
-, O17732
dependent
biotin
-
dependent on
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus, the main action of acetyl-CoA is to enhance the rate of the carboxylation of biotin in the overall reaction
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus
biotin
-
dependent on
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus
biotin
-
dependent on
biotin
-
dependent on, biotin is covalently attached to a specific lysine residue located about 35 residues from the C-terminus
biotin
-
covalently attached to Lys1112
additional information
-
enzyme activities of PC-(BC) and PC-(CT+BCCP) are not dependent on acetyl-CoA
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Co2+
-
divalent cation required, activates with 58% of the efficiency relative to Mg2+
Co2+
-
divalent metal required, Mg2+, Mn2+ or Co2+
Co2+
-
can poorly replace Mg2+
Co2+
-
can replace Mg2+ with little efficiency
Cs+
-
monovalent cation required, order of efficiency: Rb+, K+, Cs+/ NH4+
K+
-
monovalent cation required, order of efficiency: Rb+, K+, Cs+/ NH4+
K+
-
required
K+
-
increases activity by a maximum of 27% at 70 mM
K+
-
monovalent cations activate, NH4+ or K+
K+
-
monovalent cations activate, K+ is the best
K+
-
activates; Km: 20 mM
KCl
-
optimal concentration: 0.175 mM, activates at lower concentrations, inhibits at higher concentrations
KCl
-
1.6fold stimulation at 20 mM
Mg2+
-
divalent cation required, Mg2+ is most effective, Km: 0.44 mM
Mg2+
-
Km: 0.44 mM; required
Mg2+
-
Km: 0.36 mM; required
Mg2+
-
activates; Km: 0.7 mM
Mg2+
-
activates
Mg2+
-
activates; Km: 0.3 mM
Mg2+
-
activates; equally active with Mn2+ or Mg2+
Mg2+
-
activates; maximally active in presence of Mn2+
Mg2+
-
activates; the presence of MgCl2 in excess of ATP produces a more than 3fold activation
Mg2+
-
activates phosphorylation of MgADP2- by carbamyl phosphate
Mg2+
-
completely dependent on divalent metal ion, Mg2+ or Mn2+
Mg2+
-
divalent metal required, Mg2+, and with lower efficiency Mn2+ or Co2+
Mg2+
-
required, inhibits at higher concentrations
Mg2+
-
10 mM
Mg2+
-
requirement
Mg2+
-
-
Mg2+
-
the biotin carboxylase domain requires divalent cations for binding of the ATP substrate and for catalysis
Mg2+
-
required
Mg2+
-
required for activity
Mg2+
-
required for activity
Mn2+
-
divalent cation required, activates with 66% of the efficiency relative to Mg2+
Mn2+
-
3fold activation in presence of MnCl2 equimolar in concentration to ATP
Mn2+
-
does not participate directly in the reaction mechanism, but may play a structural role essential to the integrity of the enzymes tetrameric structure
Mn2+
-
divalent metal ion required, Mg2+ or Mn2+. Mn2+ inhibits at concentrations above 1.25 mM
Mn2+
-
-
Mn2+
-
each subunit contains one tightly bound metal ion, predominantly Mn2+, or mixtures of Mn2+ and Mg2+
Mn2+
-
divalent metal required, Mg2+, Mn2+ or Co2+
Mn2+
-
can poorly replace Mg2+
Mn2+
-
can replace Mg2+ with little efficiency
Mn2+
-
the carboxytransferase domain contains a tightly bound Mn2+
MnCl2
-
7.5 mM, can partially replace MgCl2
NH4+
-
monovalent cation required, order of efficiency: Rb+, K+, Cs+/ NH4+
NH4+
-
increases activity by a maximum of 39% at 80 mM
NH4+
-
monovalent cations activate, NH4+ or K+
Rb+
-
monovalent cation required, Rb+ is most effective
Zinc
-
contains a tightly bound zinc atom per subunit of the tetramer. The metal has a role in catalysis but not apparently in the maintenance of the gross protein structure
Zinc
-
contains 4 atoms of zinc per molecule
Zinc
-
each subunit contains one tightly bound Zn2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
inactivation follows pseudo-first-order kinetics, the rate of inactivation is greater at low enzyme concentrations
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate
-
inhibitor with respect to MgATP2-
2-oxoadipate
-
-
2-oxoglutarate
-
L-Asp at low concentrations it enhances the effectiveness of inhibition by 2-oxoglutarate
2-oxoglutarate
-
competitive with respect to pyruvate and at lower concentrations uncompetitive with respect to HCO3-
2-oxoglutarate
-
-
2-oxoglutarate
-
less than 10% inhibition at 5 mM
4-Acetamido-4'-(iodoacetyl)-aminostilbene-2,2'-disulfonic acid
-
-
acetyl-CoA
-
0.1 mM
ADP
-
competitively with ATP
ADP
-
27% inhibition at 5 mM
ATP
-
at concentrations above saturating, MgATP2- activates bicarbonate-dependent ATP cleavage, but inhibits the overall reaction
Avidin
-
strong
-
Avidin
-
-
-
Avidin
-
100 molar excess amount completely inhibits after 5 min
-
Co2+
-
at excess concentrations
CTP
-
in presence of ATP
Formycin A 5'-triphosphate
-
-
GTP
-
in presence of ATP
HgCl2
-
addition of Cys results in restoration of significant activity
Hydroxypyruvate
-
-
iodoacetate
-
-
ITP
-
in presence of ATP
KCl
-
activates at lower concentrations, inhibits at higher concentrations
L-Asp
-
enhances the rate of inactivation observed on incubation at 4 C in the presence of 0.5 M KCl. At low concentrations it enhances the effectiveness of inhibition by 2-oxoglutarate
L-Asp
-
competitive with respect to HCO3-, non-competitive with respect to pyruvate and MgATP2-
L-Asp
-
antagonizes activation by acetyl-CoA
L-aspartate
-
activity decreases sharply as the aspartate concentration increases up to 20 mM, beyond that point the activity decreases with a slower effect, 20% remaining activity at 20 mM
L-aspartate
-
6.4% inhibition at 10 mM
L-aspartate
-
47% inhibition at 10 mM
L-cystine
-
-
L-glutamate
-
less than 10% inhibition at 5 mM
Mercuric acetate
-
addition of Cys results in restoration of significant activity
Methanesulfonyl-CoA
-
activation
Methanesulfonyl-CoA
-
-
Methanesulfonyl-CoA
-
activation
Methylphosphonate
-
-
Mg2+
-
when Mg2+ concentration in the assay exceeds that of ATP
Mg2+
-
at excess concentrations
MgATP2-
-
substrate inhibition
Mn2+
-
inhibition above 1.25 mM, activation below
N-(7-Dimethylamino-4-methyl-3-coumarinyl)maleimide
-
-
NaCl
-
slight inhibition at 20 mM
o-phthalaldehyde
-
-
oxaloacetate
-
-
oxaloacetate
-
inhibition below 1 mM
Oxamate
-
substrate inhibition
p-hydroxymercuribenzoate
-
-
phenylacetate
-
weak inhibitor
phenylacetate
-
treatment of cultured 3T3-L1 adipocytes. Inhibiting the enzyme over several days does not alter the adipocyte differentiation program. The main metabolic effects are to up-regulate intracellular lipolysis and decrease triglyceride accumulation. Inhibition also up-regulates glycolysis
phenylacetic acid
-
inhibition at 5 mM
phenylacetic acid
-
-
phenylmercuric acetate
-
-
pyruvate
-
substrate inhibition
Sodium benzoate
-
-
sulfhydryl reagents
-
effects of ATP, acetyl-CoA, and oxalacetate on the rates of inactivation of pyruvate carboxylase by sulfhydryl reagents depend upon the anion present, the reagent used, and the phase of inactivation considered. Protection by acetyl-CoA is cooperative
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
Trinitrobenzenesulfonate
-
inactivation of acetyl-CoA dependent activity, no effect on activator-independent activity
Trinitrobenzenesulfonate
-
-
Trinitrobenzenesulfonate
-
acetyl-CoA and adenosine 3',5'-diphosphate decrease the rate of loss of activity
Trinitrobenzenesulfonate
-
acetyl-CoA and adenosine 3',5'-diphosphate protect
UTP
-
in presence of ATP
Mn2+
-
at excess concentrations
additional information
-
L-Asp and 2-oxoglutarate occupy distinct regulatory sites on Aspergilus nidulans enzyme
-
additional information
-
inhibition with physiological amounts of amino acids or dicarboxylate is not obtained
-
additional information
-
insensitive to inhibition by di- and tricarboxylic acids
-
additional information
-
no inhibitors: glutamate and alpha-ketoglutarate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate
-
allosteric activator of pyruvate carboxylase. The increase in activity between 2 mM and saturating MgATP is approximately 16fold
acetoacetyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
acetyl CoA
-
activates
acetyl CoA
-
enzyme activator, major effect is to promote the carboxylation of biotin, reduces the Kms for both MgATP2- and biotin, overview
acetyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanoyl-CoA, n-butanoyl-CoA, malonyl-CoA, CoA, acetoacetyl-CoA, oleoyl-CoA; best activator
acetyl-CoA
-
allosteric activator. Concentrations eliciting maximal activity are 0.013 mM, 0.042 mM and 0.084 mM at assay temperatures of 45C, 55C, and 65C respectively
acetyl-CoA
-
activates in presence of either L-Asp or 2-oxoglutarate but does not activate in absence of these dicarboxylic acids. Trinitrobenzenesulfonate causes selective loss of the capacity for activation by acetyl-CoA
acetyl-CoA
-
-
acetyl-CoA
-
powerful activator
acetyl-CoA
-
activates
acetyl-CoA
-
activates; best activator; in absence of acetyl-CoA the maximal rate of oxaloacetate synthesis is 20% of that obtained in presence of saturating concentrations of acetyl-CoA
acetyl-CoA
-
activates
acetyl-CoA
-
activates; in absence of acetyl-CoA the maximal rate of oxaloacetate synthesis is 4% of that obtained in presence of saturating concentrations of acetyl-CoA
acetyl-CoA
-
no effect
acetyl-CoA
-
activates
acetyl-CoA
-
inactive in absence of acetyl-CoA
acetyl-CoA
-
activates; 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
acetyl-CoA
-
activates phosphorylation of MgADP2- by carbamoyl phosphate
acetyl-CoA
-
quite active in absence of acetyl-CoA
acetyl-CoA
-
highly dependent on
acetyl-CoA
-
activates, half-maximal activity at 0.23 mM
acetyl-CoA
-
allosteric activator, 50% of maximal activity at 0.013 mM for the recombinant enzyme and at 0.015 mM for the liver enzyme
acetyl-CoA
-
activation by short-chain derivatives of CoA
acetyl-CoA
-
activates Pyc1 at 0.25 mM
acetyl-CoA
-
dependent, half maximal activation at 0.014 mM
acetyl-CoA
-
activates the conversion of pyruvate to oxaloacetate
acetyl-CoA
-
allosteric activator of pyruvate carboxylase, there is a 7fold increase in the turnover number for ATP cleavage induced by acetyl-CoA
acetyl-CoA
-
-
acyl-CoA derivatives
-
long chain acyl CoA is more effective than acetyl-CoA
acyl-CoA derivatives
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
acyl-CoA derivatives
-
activate
Butyryl-CoA
-
can replace acetyl-CoA with little efficiency
L-aspartate
-
allosteric activator
malonyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
Methanesulfonyl-CoA
-
activates
Methanesulfonyl-CoA
-
inhibition
n-butanoyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
n-propanoyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
oleoyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
palmitoyl-CoA
-
activated by long-chain acyl-CoA derivatives
propionyl-CoA
-
activates less efficiently than acetyl-CoA
propionyl-CoA
-
can replace acetyl-CoA with little efficiency
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
Methanesulfonyl-CoA
-
activates
additional information
-
acetyl-CoA and K+ have no effect on ADP phosphorylation by carbamoyl phosphate
-
additional information
-
activity strongly influenced by the carbon source used for growth
-
additional information
-
starvation enhances pyruvate carboxylase activity. Short-term treatment with glucagon increases pyruvate carboxylase mRNA but does not result in an apparent change in protein levels or activity. Pyruvate carboxylase and PEP carboxykinase acts cooperatively
-
additional information
-
starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
additional information
-
starvation enhances pyruvate carboxylase activity. Peroxisome-proliferator-activated receptor gamma increases enzyme expression in adipocytes. Rosiglitazone or other thiazolidinediones induce the enzyme expression. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
additional information
-
starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.04
-
ATP
-
-
0.05
-
ATP
-
pH 7.8, 30C, C249A mutant
0.056
-
ATP
-
pH 7.8, 30C, wild-type Pyc1
0.07
-
ATP
-
pH 7.8, 30C, wild-type Pyc1
0.07
-
ATP
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
0.2
-
ATP
-
37C and 45C, pH 8, Mg2+ concentration higher than ATP concentration
0.22
-
ATP
-
37C, pH 7.8, liver enzyme
0.24
-
ATP
-
pyruvate
0.25
-
ATP
-
37C, pH 7.8, recombinant enzyme
0.374
-
ATP
-
80C, pH 8.5
0.46
0.87
ATP
-
pH 8, 30C
0.54
1.03
ATP
-
pH 8, 30C, ATP-cleavage in absence of pyruvate
1.26
-
ATP
-
37C, pH 8, Mg2+ concentration equal to that of ATP
9.2
-
ATP
-
45C, pH 8, Mg2+ concentration equal to that of ATP
3.3
-
biotin
-
pH 7.8, 30C, in presence of acetyl-CoA
18
-
biotin
-
pH 7.8, 30C, in absence of acetyl-CoA
1.7
-
Carbamoyl phosphate
-
pH 7.8, 30C, C249A mutant, with acetyl-CoA and K+
10.7
-
Carbamoyl phosphate
-
pH 7.8, 30C, C249A mutant, without acetyl-CoA and K+
11.3
-
Carbamoyl phosphate
-
pH 7.8, 30C, wild-type Pyc1, with acetyl-CoA and K+
12.3
-
Carbamoyl phosphate
-
pH 7.8, 30C, wild-type Pyc1, without acetyl-CoA and K+
0.22
-
HCO3-
-
80C, pH 8.5
0.27
-
HCO3-
-
-
0.27
-
HCO3-
-
pyruvate
0.33
-
HCO3-
-
MgATP2-
0.66
-
HCO3-
Leptosphaeria michotii
-
-
1.36
-
HCO3-
-
pH 7.8, 30C, wild-type Pyc1
1.36
-
HCO3-
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
1.5
-
HCO3-
-
-
1.75
-
HCO3-
-
37C, pH 7.8, recombinant enzyme
2.3
-
HCO3-
-
pH 7.8, 30C, C249A mutant
2.6
-
HCO3-
-
with 10 mM free Mg2+
2.7
-
HCO3-
-
-
3
-
HCO3-
-
37C, pH 8
3.2
-
HCO3-
-
37C, pH 7.8, liver enzyme
3.3
-
HCO3-
-
-
3.4
-
HCO3-
-
with 2 mM free Mg2+
4.6
-
HCO3-
-
45C, pH 8
16
-
HCO3-
-
with saturating concentrations of the activator acetyl-CoA
62.2
-
HCO3-
-
pH 8, 30C, ATP-cleavage in absence of pyruvate
400
-
HCO3-
-
without acetyl-CoA
0.027
-
MgATP2-
-
with 10 mM free Mg2+
0.08
-
MgATP2-
-
pyruvate, second values 0.21 mM
0.14
-
MgATP2-
-
-
0.19
-
MgATP2-
-
-
0.32
-
MgATP2-
-
-
0.6
-
MgATP2-
-
pH 7.8, 30C, in presence of acetyl-CoA
4.1
-
Oxamate
-
ATPase reaction, wild-type, pH 7.5, 25C
0.05
-
pyruvate
-
-
0.08
-
pyruvate
-
wild-type enzyme after retroviral expression
0.12
-
pyruvate
-
A610T mutant after retroviral expression
0.2
-
pyruvate
Leptosphaeria michotii
-
-
0.21
-
pyruvate
-
second value 0.08
0.22
-
pyruvate
-
37C, pH 7.8, liver enzyme
0.23
-
pyruvate
-
37C, pH 7.8, recombinant enzyme
0.25
-
pyruvate
-
-
0.25
-
pyruvate
-
pyruvate
0.25
-
pyruvate
-
MgATP2-, with 2 mM free Mg2+
0.26
-
pyruvate
-
-
0.26
-
pyruvate
-
pH 8
0.3
-
pyruvate
-
37C, pH 8
0.3
-
pyruvate
-
wild type
0.31
-
pyruvate
-
pH 8, 30C
0.45
-
pyruvate
-
pH 7.8, 30C, C249A mutant
0.45
-
pyruvate
-
45C, pH 8
0.48
-
pyruvate
-
-
0.495
-
pyruvate
-
pH 7.8, 30C, wild-type Pyc1
0.5
-
pyruvate
-
pH 7.8, 30C, wild-type Pyc1
0.5
-
pyruvate
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
0.53
-
pyruvate
-
80C, pH 8.5
0.58
-
pyruvate
-
wild-type, pH 7.5, presence of acetyl-CoA
1
-
pyruvate
-
ATPase reaction, wild-type, pH 7.5, 25C
1.8
-
pyruvate
-
mutant Q870A, pH 7.5
1.86
-
pyruvate
-
-
2.3
-
pyruvate
-
mutant S911A, pH 7.5
4.4
-
pyruvate
-
wild-type, pH 7.5
1.8
-
MgATP2-
-
pH 7.8, 30C, in absence of acetyl-CoA
additional information
-
additional information
-
stopped flow kinetics using fluorescent ATP analogue formycin A-5'-triphosphate, presence of biotin enhanced binding, kinetics of free biotin carboxylation
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0018
-
ATP
-
pH 7.8, 30C, absence of acetyl CoA, 0.24 mM Mg2+
0.0029
-
ATP
-
pH 7.8, 30C, absence of acetyl CoA, 10 mM Mg2+
0.0049
-
ATP
-
pH 7.8, 30C, absence of acetyl CoA, 1 mM Mg2+
0.014
-
ATP
-
pH 7.8, 30C, ATP cleavage in absence of acetyl-CoA
0.037
-
ATP
-
pH 7.8, 30C, ATP cleavage in presence of acetyl-CoA
0.054
-
ATP
-
pH 7.8, 30C, presence of acetyl CoA, 1 mM Mg2+
0.28
-
ATP
-
pH 7.8, 30C, presence of acetyl CoA, 0.24 mM Mg2+
60
-
ATP
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
0.043
-
Carbamoyl phosphate
-
pH 7.8, 30C, C249A mutant, with acetyl-CoA and K+
0.11
-
Carbamoyl phosphate
-
pH 7.8, 30C, wild-type Pyc1, with acetyl-CoA and K+; pH 7.8, 30C, wild-type Pyc1, without acetyl-CoA and K+
0.13
-
Carbamoyl phosphate
-
pH 7.8, 30C, C249A mutant, without acetyl-CoA and K+
60
-
HCO3-
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
0.28
-
pyruvate
-
mutant enzyme R548K, in 100 mM Tris-HCl pH 7.8, 30C
1.2
-
pyruvate
-
mutant Q870A, pH 7.5
2.5
-
pyruvate
-
mutant S911A, pH 7.5
6.5
-
pyruvate
-
wild-type, pH 7.5
13.9
-
pyruvate
-
wild type enzyme, in 100 mM Tris-HCl pH 7.8, 30C
15.7
-
pyruvate
-
wild-type, pH 7.5, presence of acetyl-CoA
60
-
pyruvate
P11154, P32327
30C, pH 7.8; 30C, pH 7.8
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.7
-
pyruvate
-
mutant Q870A, pH 7.5
16065
1.1
-
pyruvate
-
mutant S911A, pH 7.5
16065
1.5
-
pyruvate
-
wild-type, pH 7.5
16065
27.2
-
pyruvate
-
wild-type, pH 7.5, presence of acetyl-CoA
16065
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.89
-
ADP
-
80C, pH 8.5
2.24
-
ATP
-
45C, pH 8
5.34
-
ATP
-
80C, pH 8.5
0.4
-
MgATP2-
-
pH 7.8, 30C, in absence of acetyl-CoA
0.5
-
MgATP2-
-
pH 7.8, 30C, in presence of acetyl-CoA
0.22
-
oxaloacetate
-
pH 8
8
-
Oxamate
-
mutant enzyme Q552N, in 100 mM Tris-HCl pH 7.8, 30C
10
-
Oxamate
-
mutant enzyme R548K, in 100 mM Tris-HCl pH 7.8, 30C
10.1
-
Oxamate
-
ATPase reaction, wild-type, pH 7.5, 25C
19
-
Oxamate
-
wild type enzyme, in 100 mM Tris-HCl pH 7.8, 30C
10
-
pyruvate
-
ATPase reaction, wild-type, pH 7.5, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.002
-
-
cells grown on a phosphate-deficient medium TRP, a coupled assay with malate dehydrogenase
0.004
-
-
free biotin carboxylation activity of the mutant K1112A in absence of acetyl-CoA at 25 mM
0.005
-
-
free biotin carboxylation activity of the mutant K1112A in presence of acetyl-CoA at 25 mM
0.005
-
-
cells grown on a phosphate-sufficient minimal medium M9, a coupled assay with malate dehydrogenase
0.008
-
-
cells grown on a phosphate-deficient medium TRP, a coupled assay with malate dehydrogenase
0.03
-
-
cells grown on a phosphate-sufficient minimal medium M9, a coupled assay with malate dehydrogenase
0.05
-
-
cell extract, expressed in NZN111 after growth under CO2-atmosphere without IPTG induction
0.056
-
-
cell extract, expressed in AFP111 after growth under CO2-atmosphere without IPTG induction
0.068
-
-
cell extract, expressed in NZN111 after growth under CO2-atmosphere and induction with IPTG
0.12
-
-
cell extract, expressed in AFP111 after growth under CO2-atmosphere and induction with IPTG
0.17
-
-
cell extract, expressed in AFP111 after growth under H2-atmosphere and induction with IPTG; cell extract, expressed in NZN111 after aerobic growth without IPTG induction
0.49
-
-
cell extract, expressed in NZN111 after aerobic growth and induction with IPTG
0.587
-
-
control CHO-K1 cells
0.72
-
-
cell extract, expressed in AFP111 after aerobic growth and induction with IPTG
0.81
-
-
cell extract, expressed in AFP111 after aerobic growth without IPTG induction
1.03
-
-
-
12.1
-
-
-
18.62
-
-
-
19.43
-
-
enzyme recombinantly expressed in Pseudomonas aeruginosa
20
-
-
-
43.8
-
-
nondiabetic subjects
47.8
-
-
type 2 diabetic patients
2030
-
-
-
additional information
-
-
-
additional information
-
Leptosphaeria michotii
-
-
additional information
-
-
-
additional information
-
-
0.768-2.684 for the PYC2 clones
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.6
-
-
in presence of 5 mM Mn2+
7
-
-
around, in presence of Mn2+
7
-
-
activated by MnCl2
7.1
-
-
in presence of MnATP2-
7.1
-
-
in presence of MnCl2
7.5
-
-
assay at
7.6
8.4
-
-
7.6
-
-
in presence of 5 mM Mg2+
7.8
-
-
assay at, carboxylation of free biotin, ATP cleavage, and ADP phosphorylation by carbamoyl phosphate
8
8.5
Leptosphaeria michotii
-
-
8
-
-
activated by Mg2+, at a MgCl2 concentration double that of ATP
8.3
-
-
in presence of MgCl2
8.5
-
-
activated by Mg2+ equimolar to ATP
9
-
-
in presence of MgATP2-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
12
Leptosphaeria michotii
-
active in this range
7
9.3
-
7.0: about 65% of maximal activity, 9.3: about 35% of maximal activity
additional information
-
-
pH profiles of the ATP-cleavage reaction in the presence and absence of free biotin
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
Leptosphaeria michotii
-
-
30
-
-
assay at, carboxylation of free biotin, ATP cleavage, and ADP phosphorylation by carbamoyl phosphate
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
18
40
Leptosphaeria michotii
-
active in this range
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
tight regulation of enzyme expression with differentiation
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
moderate activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
enzyme activity is preserved in the islets of obese animals, but it is reduced in the islets of animal models of type 2 diabetes
Manually annotated by BRENDA team
-
increased activity in Zucker fatty rats
Manually annotated by BRENDA team
-
high activity
Manually annotated by BRENDA team
additional information
-
tissue-specific expression. In dairy cows, the expression of the enzyme is markedly elevated during the transition from calving to lactation
Manually annotated by BRENDA team
additional information
-
tissue-specific expression. In murine 3T3-L1 adipocytes, pyruvate carboxylase protein, its activity and mRNA are elevated in parallel with other key lipogenic enzymes, which increase concomitantly with the accumulation of lipid droplets during terminal differentiation of adipocytes
Manually annotated by BRENDA team
additional information
-
tissue-specific expression, production of specific forms of PC mRNA are linked to certain physiological states, i.e. development, gluconeogenesis and lipogenesis
Manually annotated by BRENDA team
additional information
-
expression of the two isoenzymes is differentially regulated and expressed during different growth conditions, expression of PYC1 and PYC2 is influenced by both the growth phase and carbon source, overview
Manually annotated by BRENDA team
additional information
-
tissue-specific expression
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Aquifex aeolicus (strain VF5)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Rhizobium etli (strain CFN 42 / ATCC 51251)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
Staphylococcus aureus (strain Mu50 / ATCC 700699)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
51400
-
-
chain PC-(BC), SDS-PAGE, monomeric form
65000
-
-
chain PC-(CT+BCCP), SDS-PAGE, monomeric form
66200
-
-
chain PC-(CT+BCCP), gel filtration, monomeric form
81900
-
-
chain PC-(BC), gel filtration, dimeric form
120000
-
-
SDS-PAGE
123000
-
-
SDS-PAGE
128000
-
-
intact enzyme, SDS-PAGE, monomeric form
128200
-
-
chain PC-(CT+BCCP), gel filtration, dimeric form
129300
-
-, O17732
calculated from amino acid sequence
300000
-
-
gel filtration
420000
440000
Leptosphaeria michotii
-
gel filtration, native PAGE
472000
-
-
analytical ultracentrifugation
475000
-
-
meniscus depletion sedimentation equilibrium method
480000
-
-
gel filtration, Stokes' radius
500000
-
-
-
500000
-
-
approach to equilibrium ultracentrifugation
500000
-
-
native PAGE
500000
-
-
gel filtration
501000
-
-
gel filtration
501300
-
-
intact enzyme, gel filtration, tetrameric form
537000
-
-
-
558000
-
-
gel filtration
additional information
-
-
at high enzyme concentration the enzyme aggregates to form high molecular weight aggregates
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 125000-130000, SDS-PAGE with dithiothreitol
?
-
x * 136750, SDS-PAGE
?
-
x * 136000
?
-
x * 133000, SDS-PAGE
?
-
x * 65000, alpha, + x * 54000, beta, SDS-PAGE. The alpha-polypeptides are on the outside of the molecule and the beta-polypeptides are the internal subunits
?
-
x * 125000, SDS-PAGE
?
-
x * 127370, calculation from nucleotide sequence
?
-
x * 13100, calculation from nucleotide sequence
?
-
x * 130000, SDS-PAGE
dimer
-
about 12% of the total enzyme, gel filtration
dimer
-
PC-(BC) exists as a monomer and as a dimer, (CT+BCCP) exists mostly as a dimer, gel filtration
dimer
-
1 * 50000 + 1 * 70000
homotetramer
-
analytical ultracentrifugation
monomer
-
about 10% of the total enzyme, gel filtration
multimer
-
x * 120000, SDS-PAGE
octamer
Leptosphaeria michotii
-
4 * 60000, biotin containing alpha-subunit, + 4 * 50000, biotin-free beta-subunit
octamer
-
alpha4,beta4, 4 * 55000 + 4 * 65000, the 65000 Da subunit is biotinylated, the 55000 Da subunit is not, SDS-PAGE
octamer
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
oligomer
-
two pyruvate carboxylase subunits PycA and PycB
polymer
-
about 4% of the total enzyme elutes as a high molecular weight species, gel filtration
tetramer
-
4 * 140000-155000, SDS-PAGE after denaturation by carboxylation in 7.5 M urea or in 6 M guanidine HCl, or succinylation in 7.5 M urea
tetramer
-
4 * 130000, SDS-PAGE
tetramer
-
4 * 12000, SDS-PAGE
tetramer
-
4 * 125000, SDS-PAGE
tetramer
-
4 * 130000, SDS-PAGE
tetramer
-
4 * 110000, SDS-PAGE
tetramer
-
2 * 65000 + 2 * 54000, SDS-PAGE
tetramer
-
4 * 130000, SDS-PAGE
tetramer
-
4 * 125000, SDS-PAGE
tetramer
-
4 * 130000, SDS-PAGE
tetramer
-
4 * 126000, calculation from nucleotide sequence, SDS-PAGE
tetramer
-
4 * 124700, SDS-PAGE
tetramer
-
4 * 128000, SDS-PAGE
tetramer
-
about 73% of the total enzyme, gel filtration
tetramer
-
4 * 120000, SDS-PAGE
tetramer
-
four identical subunits
tetramer
-
4 * 128500-137000, SDS-PAGE, gel filtration, intact enzyme
tetramer
P11154, -
Glu40 and Glu433 play essential roles in subunit interactions
tetramer
-
tetrameric organization of wild-type and isolated C-terminal region, the PC tetramerization, PT, domain is important for oligomerization, conserved mode of tetramerization, overview
tetramer
-
tetrameric organization of wild-type and isolated C-terminal region, the PC tetramerization, PT, domain is important for oligomerization, conserved mode of tetramerization
tetramer
Sinorhizobium meliloti Rm1021
-
4 * 120000, SDS-PAGE
-
monomer
-
PC-(BC) exists as a monomer and as a dimer, gel filtration
additional information
-
each protomer consists of two polypeptide chains, with alpha and beta subunits arranged in an (alphabeta)4 structure
additional information
-
structure analysis, the enzyme shows the alpha4beta4 form, each subunit is made up of two polypeptide chains, the 55 kDa non-biotinylated subunit alpha, which possesses the biotin carboxylase activity, and the 70 kDa beta subunit, which carries the biotin and also contains the carboxytransferase activity, overview. Dimerization interface structure, overview
additional information
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
additional information
-
structure analysis, the enzyme shows the alpha4beta4 form, each subunit is made up of two polypeptide chains, the 55 kDa non-biotinylated subunit alpha, which possesses the biotin carboxylase activity, and the 70 kDa beta subunit, which carries the biotin and also contains the carboxytransferase activity, overview
additional information
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
additional information
-
structure analysis, the enzyme shows the alpha4beta4 form, each subunit is made up of two polypeptide chains, the 55 kDa non-biotinylated subunit alpha, which possesses the biotin carboxylase activity, and the 70 kDa beta subunit, which carries the biotin and also contains the carboxytransferase activity, overview
additional information
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
additional information
-
the enzyme exists predominantly as a tetramer in solution and, while it can equilibrate between the tetramer, dimer and monomer, only the tetrameric form of the enzyme catalyses the overall reaction, subunit arrangement. All three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview. Quarternary structure, overview
additional information
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
additional information
-
the enzyme exists predominantly as a tetramer in solution and, while it can equilibrate between the tetramer, dimer and monomer, only the tetrameric form of the enzyme catalyses the overall reaction, subunit arrangement. All three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, overview
additional information
-
localization of a BCCP domain is located in the active site of the carboxytransferase domain that participates in the carboxyltransfer reaction
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
one biotin moiety is covalently attached to the side chain of a lysine residue located near the C-terminus of each protomer
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
biotin carboxylase subunit
-
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
-
complete structure of pyruvate carboxylase at 2.0 A resolution, domain architecture of pyruvate carboxylase
-
crystal structure analysis
-
in complex with coenzyme A, symmetrical tetramer with one coenzyme A molecule bound to each monomer. Presence of acetyl-CoA promotes a conformation for the dimer of the biotin carboxylase domain of pyruvate carboxylase that might be catalytically more competent
-
purified enzyme in presence of 5 mM ATP and 5 mM oxaloacetic acid, sitting drop method, room temperature, the reservoir solution contains 20% w/v PEG 3350 and 200 mM ammonium tartrate, X-ray diffraction structure determination and analysis at 2.8 A resolution
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0
-
-
10 mM potassium phosphate, 10 mM KCl, 1 mM EDTA, 0.1 mM DTT, pH 6.8, potassium phosphate-KCl buffer, 50% loss of activity after 10 min
20
-
-
1 h, 75% inactivation
45
-
-
retains all its activity after 45 min
45
-
-
10 min, complete loss of activity, half-life: 2 min
46
-
-
10 min, 50% loss of activity
50
-
-
15 min, complete loss of activity
55
-
-
half-life: 9 min. A mixture of Tris-HCl, potassium bicarbonate, sodium pyruvate, ATP, MgC2l, and acetyl-CoA at concentrations similar to those used in the enzyme assay, protect completely for at least 30 min
60
-
-
pH 7, half-life: 1 h
80
-
-
rapid inactivation, t1/2: 1 h in 100 mM Tris/HCl, pH 7, sulfate salts provide partial protection
additional information
-
-
cold inactivation
additional information
-
-
not cold labile
additional information
-
-
Tris hydrochloride, KCl or a mixture of MgCl2 and ATP protects against heat inactivation
additional information
-
-
acetyl-CoA protects against thermal inactivation
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
acetyl-CoA and sodium pyruvate protects against cold inactivation. L-Asp decreases inactivation, 1 M sucrose gives complete protection
-
the presence of KCl at 10, 20, 50, and 100 mM potassium phosphate buffer-KCl buffer at 0C leads to 85%, 44%, 17% and 0% loss of activity
-
stable to exposure to 6 M urea for up to 2.5 h at 20C
-
acetyl-CoA stabilizes quarternary structure of the enzyme
-
dilution inactivates the enzyme, inactivation can be prevented at 10 mM Mg2+
-
does not participate directly in the reaction mechanism, but may play a structural role essential to the integrity of the enzymes tetrameric structure
-
upon dilution, there is dissociation of the catalytically active tetrameric enzyme species into inactive dimers. Reactivation of the enzyme results in reassociation of enzymic dimers into tetramers.
-
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 0C in the presence of high concentrations of Cl- salts of monovalent cations. MgCl2 or sucrose prevent inactivation
-
acetyl-CoA protects against thermal denaturation
-
freezing and thawing over a 16 h period results in rapid loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0C, 10 mM potassium phosphate, 10 mM KCl, 1 mM EDTA, 0.1 mM DTT, pH 6.8, potassium phosphate-KCl buffer, 50% loss of activity after 10 min
-
4C, stable for at least 3 months
-
-20C, stable, purified enzyme, 75% activity after 5 days
-
-80C, stable, purified enzyme, 75% activity after 5 days
-
4C, stable, purified enzyme, 83-85% activity after 36 h
-
-70C, 90% activity after 1 month in the presence of 10% inositol, 30% loss of activity after 24 h without inositol
-
4C, 90% activity after 1 month in the presence of 10% inositol, 30% loss of activity after 24 h without inositol
-
quarternary structure is quite stable in absence o acetyl-CoA
-
-20C, pH 7.8, 2 weeks, 40% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial
-
recombinant His9-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by affinity chromatography
-
recombinant C-terminal region from Escherichia coli strain BL21(DE3)
-
recombinant enzyme and enzyme from liver
-
-
Leptosphaeria michotii
-
rapid purification methods
-
Co2+-affinity column chromatography
-
HisPur cobalt resin column chromatography
-
rapid dye-ligand affinity chromatography procedure
-
Pyc1 isoform and C249A mutant
-
Pyc1 isoform, 88% purity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli JM109
-
expression in Escherichia coli ptsG mutant
-
DNA and amino acid sequence determination and analysis, identification of promoter regions of bovine pyruvate carboxylase, putative transcription factor binding sites of promoter P1 and of P2, overview
Q29RK2
key cognate transcription factors regulating tissue-specific expression. The proximal promoter of the bovine PC gene mediates the mRNA variants that are restricted to gluconeogenic and lipogenic tissues, transcriptional regulation, overview
-
the enzyme is expressed in 6 alternatively spliced variants that share a common ORF but differ in the 5'UTRs, resulting in different translational efficiencies, overview. In vitro transcription and translation by rabbit reticulocyte lysate as luciferase-linked protein, functional synthesis of luciferase, overview
-
wild-type and mutants without enzyme activity
-
DNA and amino acid sequence determination and analysis, expression mutant ezymes and of the isolated biotin carboxylase domain
-
expression in Escherichia coli JM109
-
expression of His9-tagged wild-type and mutant enzymes in Escherichia coli strain BL21
-
expression of the subunits biotin carboxylase BC and carboxyl transferase CT (PC-(BC+CT)) and biotin carboxyl carrier protein BCCP (PC-(BCCP)) in Escherichia coli JM109
-
two polypeptide chain: PC-(BC) and PC-(CT+BCCP)
-
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
-
expression in Escherichia coli GJT001, coexpression with pantothenate kinase
-
expression in Escherichia coli mutant SBS110MG
-
expression in Escherichia coli wild-type GJT001 and mutants YBS121
-
DNA and amino acid sequence determination and analysis, genetic structure, key cognate transcription factors regulating tissue-specific expression, transcriptional regulation, overview
-
a Pseudomonas aeruginosa strain carrying the T7 polymerase gene can serve as a host for the overexpression of Mycobacterium smegmatis alpha4 under the control of the T7 promoter from a broad-host-range conjugative plasmid. Overexpression occurrs both in aerobic (LB medium) and nitrate-respiring anaerobic (LB medium plus glucose and nitrate) cultures. The latter system presents a simpler option because it involved room temperature cultures in stationary screw-cap bottles. Developed of a Pseudomonas aeruginosa DELTApyc strain that allows the expression of recombinant PYCs in the absence of the native enzyme; a Pseudomonas aeruginosa strain carrying the T7 polymerase gene can serve as a host for the overexpression of Pseudomonas aeruginosa alpha4beta4 PYC under the control of the T7 promoter from a broad-host-range conjugative plasmid. Overexpression occurs both in aerobic (LB medium) and nitrate-respiring anaerobic (LB medium plus glucose and nitrate) cultures. The latter system presents a simpler option because it involved room temperature cultures in stationary screw-cap bottles. Development of a Pseudomonas aeruginosa DELTApyc strain that allows the expression of recombinant PYCs in the absence of the native enzyme
-
genes pycA and pycB encoding two subunits are divergently transcribed upstream of pycR encoding for a pyruvate carboxylase regulator PycR, genomic organization of the PA5436-5435, pycAB, operon and the PA5437 or pycR gene, 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 analysis of the enzyme in diverse wild-type and knockout insulinoma cell lines, overview
-
stable overexpression in enzyme-deficient INS-1 insulinoma cell line
-
DNA and amino acid sequence determination and analysis
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli NZN111 and AFP111
-
coexpressed with human erythropoietin in BHK-21 cells
-
coexpression of pyruvate carboxylase 1 isozyme (Pyc1) with an N-terminal myc tag, together with constructs encoding either the biotin carboxylase domain or the transcarboxylase-biotin carboxyl carrier domain, each with an N-terminal 9-histidine tag
P11154, -
expression in CHO-K1-hGM-CSF cells
-
Pyc1 isoform and C249A mutant
-
two genes PYC1 and PYC2 located on different chromosomes, expression of PYC1 and PYC2 is influenced by both the growth phase and carbon source, overview
-
DNA and amino acid sequence determination and analysis
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of pyruvate carboxylase is be increased 2-5fold at the onset of obesity in Zucker fatty rats
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D543E
-
mutant with decreased activity
D649N
-
mutant with decreased activity
D713E
-
mutant with decreased activity
D713N
-
mutant with decreased activity
D762E
-
mutant with decreased activity
D762N
-
mutant with decreased activity
E576D
-
mutant with decreased activity
E576Q
-
mutant with decreased activity
E592Q
-
mutant with decreased activity
K1112A
-
site-directed mutagenesis, the mutant lacks the biotin binding site and boud biotin, it does not catalyse the complete reaction, but catalyses ATP-cleavage and the carboxylation of free biotin. Oxaloacetate decarboxylation is not catalysed, even in the presence of free biotin, suggesting that only the biotin carboxylation domain of the enzyme is accessible to free biotin. The mutant K1112A also catalyses the phosphorylation of ADP from carbamoyl phosphate
K712Q
-
mutant with decreased activity
A610T
-
reduced enzyme activity, no import of the enzyme into mitochondria
A610T
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant's catalytic activity and steady-state level are markedly decreased
F1077A
-
mutant cyrstal structure, overview
R451C
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant enzyme shows markedly decreased acetyl-CoA-dependent activation
K119Q
-
no catalytic acitivy for pyruvate decarboxylation, or oxaloacetate decarboxylation
K718Q
-
2.9% of wild-type activity for pyruvate carboxylation, 14% for full reverse reaction, 7.2% for oxaloacetate decarboxylation in presence of oxamate
Q552A
-
the mutation results in loss of the ability to catalyse pyruvate carboxylation, biotin-dependent decarboxylation of oxaloacetate and proton exchange between pyruvate and water
Q552N
-
the mutation results in loss of the ability to catalyse pyruvate carboxylation, biotin-dependent decarboxylation of oxaloacetate and proton exchange between pyruvate and water
Q844L/S885A
-
13% of wild-type activity for pyruvate carboxylation, 53% for full reverse reaction, 4.7% for oxaloacetate decarboxylation in presence of oxamate
R472S
-
the mutation severely decreases the affinity of the enzyme for acetyl-CoA
R548A
-
the mutation results in loss of the ability to catalyse pyruvate carboxylation, biotin-dependent decarboxylation of oxaloacetate and proton exchange between pyruvate and water
R548K
-
the mutation results in loss of the ability to catalyse pyruvate carboxylation (2% residual activity), biotin-dependent decarboxylation of oxaloacetate and proton exchange between pyruvate and water
T882A
-
no catalytic activity for reactions involving the carboxyl transferase domain. 7- and 3.5fold increases in activity, as compared to that of the wild-type enzyme, for the ADP phosphorylation and bicarbonate-dependent ATPase reactions, respectively. Partial inhibition of the T882A-catalyzed biotin carboxylase domain reactions by oxamate and pyruvate
T882C
-
7.1% of wild-type activity for pyruvate carboxylation, 20% for full reverse reaction, 11% for oxaloacetate decarboxylation in presence of oxamate
T882S
-
21% of wild-type activity for pyruvate carboxylation, 51% for full reverse reaction, 30% for oxaloacetate decarboxylation in presence of oxamate
C249A
-
only small effects on enzyme activity
E40R
P11154, -
predominant form of mutant E40R is the monomer. Coexpression of mutant forms with wild type Pyc1 shows that mutations causes severe loss of interaction with wild type Pyc1
R36E
P11154, -
the R36E is much more susceptible to tetramer dissociation and inactivation than the wild type enzyme. Coexpression of mutant forms with wild type Pyc1 shows that the R36E mutation had no effect on the interaction of these subunits with those of wild type Pyc1
A610T
-
more than 30fold loss in catalytic efficiency
K912T
-
more than 30fold loss in catalytic efficiency
Q870A
-
2fold loss in catalytic efficiency
R644A
-
more than 30fold loss in catalytic efficiency
R644K
-
more than 30fold loss in catalytic efficiency
S911A
-
1.5fold loss in catalytic efficiency
T908A
-
more than 30fold loss in catalytic efficiency
Y651A
-
more than 30fold loss in catalytic efficiency
additional information
-
a chimeric enzyme mutant, comprising the biotin carboxylase domain of the enzyme from Aquifex aeolicus and the transcarboxylation and BCCP domain from Bacillus thermodenitrificans, shows an activity that is independent of acetyl-CoA, a characteristic of the Aquifex aeolicus enzyme and not the Bacillus thermodentrificans enzyme
K712R
-
mutant with decreased activity
additional information
-
polypeptide chain is divided into two chains, between the biotin carboxylase and carboxyltransferase domains, resulting in two proteins PC-(BC) and PC-(CT+BCCP) with retained enzyme activity
additional information
-
construction of an enzyme mutant form, in which the lysine residue to which the biotin is normally covalently bound is mutated to an alanine residue, this results in the production of an unbiotinylated apo-enzyme, which can, however, carboxylate free biotin in a reaction that proceeds 8fold faster in the presence of acetyl-CoA than in its absence. A chimeric enzyme mutant, comprising the biotin carboxylase domain of the nezyme from Aquifex aeolicus and the transcarboxylation and BCCP domain from Bacillus thermodenitrificans, shows an activity that is independent of acetyl-CoA, a characteristic of the Aquifex aeolicus enzyme and not the Bacillus thermodentrificans enzyme
M743I
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
additional information
-
three forms of PC deficiency are classified. Type A or the North American phenotype is caused by several point mutations and characterized by a mild lactic acidaemia but a normal ratio of plasma lactate to pyruvate, psychomotor retardation and in some, but not all cases, death in the first years of life. type B phenotype, a complex genotype in which two deletion mutations in both PC alleles was identified, i.e. one allele possesses two nucleotide deletions in exon 16, creating a frameshift mutation, whereas the other allele possesses four nucleotide deletions in intron 15, resulting in an aberrant transcript. These two mutations generate premature terminations of the protein. The type C or benign phenotype is characterized as a mild lactic acidosis but normal psychomotor development
additional information
-
molecular basis of pyruvate carboxylase deficiency, mosaicism correlates with prolonged survival, three clinical phenotypes: type A is an infantile form, type B is a neonatal form, and type Casa benign form. Analysis of combinations of missense mutations, deletions, a splice site substitution and a nonsense mutation, overview
V145A
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
additional information
-
transgenic mice carrying a dominant-negative mutant CREB show a global reduction of gluconeogenic enzymes including PC, PEPCK and glucose 6-phosphatase
additional information
-
deletion of the PC gene in this yeast impairs alcohol oxidase activity, causing the accumulation of inactive alcohol oxidase in the cytosol
Y542V/A557Q/S762D
-
the triple mutation fully inactivates the moonlighting function of Pyc1, but not the enzyme activity of pyruvate carboxylase
additional information
-
mutant strain STM5437contains an insertion in the PA5437 or pycR gene encoding for a pyruvate carboxylase regulator, PycR inactivation results in 100000fold attenuation of virulence in the rat lung in vivo, 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
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
E433R
P11154, -
predominant form of mutant E433R is the monomer. Coexpression of mutant forms with wild type Pyc1 shows that mutations causes severe loss of interaction with wild type Pyc1
additional information
P11154, P32327
construction of chimeric enzymes of Pyc1 and Pyc2; construction of chimeric enzymes of Pyc1 and Pyc2
additional information
-
50% down-regulation of the enzyme in the RTG1 and the RTG2 mutants
R36E/E433R
P11154, -
predominant form of mutant R36E/E433R is the monomer. Coexpression of mutant forms with wild type Pyc1 shows that mutations causes severe loss of interaction with wild type Pyc1
additional information
Saccharomyces cerevisiae DM18
-
construction of chimeric enzymes of Pyc1 and Pyc2; construction of chimeric enzymes of Pyc1 and Pyc2
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
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
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pyruvate decarboxylase deficiency is an autosomal, recessively inherited disease, patients have less than 5% of normal enzyme activity. Four single point mutations are responsible for some forms of the disease: V145A, R451C, A610T and M743I
medicine
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A610T mtation leads to type A pyruvate carboxylase deficiency, no import of the enzyme into mitochondria
medicine
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identification of mutations of the pyruvate carboxylase gene, in five unrelated patients. Pyruvate deficiency form B is consistently associated with at least one truncating mutation, mostly lying in the C-terminal part of carboxyltransferase or BCCP domains, whereas form A always results from association of two missense mutations located in biotin carboxylase or N-terminal part of carboxyltransferase domains. Although most pyruvate carboxylase mutations are suggested to interfere with biotin metabolism, none of the newly identified pyruvate carboxylase-deficient patients is biotin-responsive
medicine
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in lung tumor tissue, pyruvate carboxylase shows increased levels of protein and mRNA
medicine
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induction of pyruvate decarboxylase during chronic suppression of glutamine metabolism is a mechanism of resistance to therapies targeting glutaminolysis
medicine
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in mildly hyperglycemic type 2 diabetic Agouti-K mice, islet pyruvate carboxylase activity, but not protein level, is increased 1.7fold. In severely hyperglycemic type 2 diabetic Agouti-K mice, islet pyruvate carboxylase activity and protein level are reduced. all other changes including insulin secretion and islet morphology in diabetic Agouti K mice are similar to those of obese Agouti mice
medicine
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treatment of cultured 3T3-L1 adipocytes with inhibitor phenylacetate. Inhibiting the enzyme over several days does not alter the adipocyte differentiation program. The main metabolic effects are to up-regulate intracellular lipolysis and decrease triglyceride accumulation. Inhibition also up-regulates glycolysis. The reduction in triglycerides is due to decreased de novo fatty acid synthesis. Exogenous addition of free fatty acids dose-dependently increases the cellular triglyceride level in the inhibitor-treated adipocytes, but not in untreated control cells
biotechnology
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coexpression of recombinant pyruvate coarboxylase in BHK-21 cells improves the production of human erythropoietin in a continuously perfused bioreactor