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Information on EC 6.4.1.1 - pyruvate carboxylase
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EC Tree
6.4.1.1 pyruvate carboxylaseIUBMB Comments
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
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Word Map
- 6.4.1.1
- phosphoenolpyruvate
-
gluconeogenesis
-
carboxykinase
- biotin
- oxaloacetate
- acetyl-coa
-
tricarboxylic
-
gluconeogenic
-
anaplerotic
- malate
- citrate
- tca
- co2
-
malic
- pepck
- carboxylases
- astrocyte
- glucose-6-phosphatase
-
biotin-dependent
- acidosis
- propionyl-coa
-
citric
-
krebs
- glutamicum
-
bark
- pine
-
biotin-containing
-
13c-labeled
-
propionyl
-
isotopomer
-
maritime
-
1-13cglucose
- avidin
- hyperammonemia
-
fructose-1,6-diphosphatase
- carboxyltransferase
-
pyrogenic
-
4.1.1.32
-
1,6-bisphosphatase
- holocarboxylase
- transcarboxylase
- biotinidase
-
pyrolytic
- leigh
-
ureagenesis
- medicine
-
glucogenic
- biotechnology
- penicillinase
-
13c-enriched
- pinaster
- synthesis
- 3-methylcrotonyl-coa
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
pyruvate carboxylase, pyc, pcase, hppyc1p, pyruvate carboxylase 1, pyc1p, pyruvic carboxylase, ehpyc1, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Carboxylase, pyruvate
-
-
-
-
HpPyc1p
Mfla_1512
MSmeg_2412
PC
PCB
-
-
-
-
PYC
Pyc1
PYC2
pycA
pyruvate carboxylase
Pyruvic carboxylase
-
-
-
-
RePC
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
mechanism
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
mechanism
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
mechanism
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
Methanococcus sp.
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
reaction mechanism of ATP cleavage and biotin carboxylation, overview
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
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
-
ATP + pyruvate + HCO3- + H+ = ADP + phosphate + oxaloacetate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylation
-
-
-
-
cleavage of C-N-linkage
hydrolysis of peptide bond
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PATHWAY SOURCE
PATHWAYS
KEGG
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SYSTEMATIC NAME
IUBMB Comments
pyruvate:carbon-dioxide ligase (ADP-forming)
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
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CAS REGISTRY NUMBER
COMMENTARY
9014-19-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ADP + carbamoyl phosphate
ATP + ?
-
at 0.3% of the rate obtained from pyruvate-carboxylation
-
-
?
ADP + carbamoylphosphate
?
reverse reaction is assessed by using substrate analogue carbamoylphosphate
-
-
r
ADP + carbamoylphosphate
?
reverse reaction is assessed by using substrate analogue carbamoylphosphate
-
-
r
ATP + pyruvate + HCO3-
?
-
pyruvate carboxylase deficiency in humans causes severe acidosis
-
-
?
ATP + pyruvate + HCO3-
?
Leptosphaeria michotii
-
one of the enzymes of the asparagine-pyruvate pathway
-
-
?
ATP + pyruvate + HCO3-
?
-
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-
?
-
enzyme is necessary for growth in minimal medium with pyruvate as sole carbon source
-
-
?
ATP + pyruvate + HCO3-
?
-
enzyme synthesis is induced by pyruvate and repressed by tricarboxylic acid cycle intermediates
-
-
?
ATP + pyruvate + HCO3-
?
-
meets anaplerotic and/or biosynthetic needs in metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
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
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
anaplerotic enzyme for growth on carbohydrates, reaction is a major bottleneck for amino acid production
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
role of anaplerosis in the central carbon metabolism and amino acid synthesis
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
cells containing the enzyme yield significantly more cell mass while generating less acetate
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
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
-
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
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
the enzyme 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
-
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
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
-
role in gluconeogenesis, lipogenesis, biosynthesis of neurotransmitter substances and in glucose-induced insulin secretion by pancreatic islets
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
anaplerotic enzyme
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
pyruvate carboxylase, and thereby anaplerosis, is crucial for an appropriate rise in the ATP:ADP ratio in response to fuel metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the enzyme is involved in mitochondrial metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
essential for normal growth
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
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
-
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
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
-
ATP in form of MgATP2-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, and other cellular processes
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
involvement of several ionisable residues in both ATP-cleavage and biotin carboxylation
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
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
-
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
Methanococcus sp.
-
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
-
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
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
-
-
-
?
additional information
?
-
-
HCO3--dependent ATP cleavage catalyzed in absence of pyruvate
-
-
?
additional information
?
-
-
ATP cleavage by the recombinantly expressed isolated biotin carboxylase domain, overview
-
-
?
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
?
-
-
the enzyme in adipocytes interacts with prohibitin, a protein involved in mitochondrial biogenesis
-
-
?
additional information
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
additional information
?
-
-
the transcarboxylase domain of pyruvate carboxylase is essential for assembly of the peroxisomal flavoenzyme alcohol oxidase
-
-
?
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
?
-
-
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
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
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
?
-
beta-cells possess compensatory systems that are activated in response to suppression of pyruvate carboxylase nzyme levels. The compensatory events include allosteric activation of pyruvate carboxylase due to increased levels of acetyl-CoA and enhanced conversion of isocitrate to 2-oxoglutarate and downstream metabolites via the cytosolic, NADP-dependent isocitrate dehydrogenase
-
-
?
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase rats
-
-
?
additional information
?
-
-
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate is no substrate
-
-
?
additional information
?
-
in the absence of the biotin carboxylase domain, oxamate-stimulated decarboxylation of oxaloacetate, reaction of EC 4.1.1.3, proceeds through a simple ping-pong bi bi mechanism
-
-
?
additional information
?
-
-
in the absence of the biotin carboxylase domain, oxamate-stimulated decarboxylation of oxaloacetate, reaction of EC 4.1.1.3, proceeds through a simple ping-pong bi bi mechanism
-
-
?
additional information
?
-
Rhizobium etli ATCC 51251
in the absence of the biotin carboxylase domain, oxamate-stimulated decarboxylation of oxaloacetate, reaction of EC 4.1.1.3, proceeds through a simple ping-pong bi bi mechanism
-
-
?
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
?
-
thermodynamic activation parameters for the pyruvate carboxylase-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA
-
-
?
additional information
?
-
-
thermodynamic activation parameters for the pyruvate carboxylase-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA
-
-
?
additional information
?
-
thermodynamic activation parameters for the pyruvate carboxylase-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate + HCO3-
?
-
pyruvate carboxylase deficiency in humans causes severe acidosis
-
-
?
ATP + pyruvate + HCO3-
?
Leptosphaeria michotii
-
one of the enzymes of the asparagine-pyruvate pathway
-
-
?
ATP + pyruvate + HCO3-
?
-
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-
?
-
enzyme is necessary for growth in minimal medium with pyruvate as sole carbon source
-
-
?
ATP + pyruvate + HCO3-
?
-
enzyme synthesis is induced by pyruvate and repressed by tricarboxylic acid cycle intermediates
-
-
?
ATP + pyruvate + HCO3-
?
-
meets anaplerotic and/or biosynthetic needs in metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
-
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
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
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
anaplerotic enzyme for growth on carbohydrates, reaction is a major bottleneck for amino acid production
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
role of anaplerosis in the central carbon metabolism and amino acid synthesis
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
cells containing the enzyme yield significantly more cell mass while generating less acetate
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
the enzyme 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
-
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
-
role in gluconeogenesis, lipogenesis, biosynthesis of neurotransmitter substances and in glucose-induced insulin secretion by pancreatic islets
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
anaplerotic enzyme
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
pyruvate carboxylase, and thereby anaplerosis, is crucial for an appropriate rise in the ATP:ADP ratio in response to fuel metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the enzyme is involved in mitochondrial metabolism
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
essential for normal growth
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
-
-
r
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
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
-
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
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
-
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
the enzyme catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, and other cellular processes
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview. The enzyme is allosterically regulated by acetyl-CoA and aspartate. In addition to de novo fatty acid synthesis, pyruvate carboxylase is also involved in glyceroneogenesis, a pathway for synthesizing glycerol required for fatty acid re-esterification. Physiological functions and regulation, overview
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
-
-
-
?
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
-
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
-
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
Methanococcus sp.
-
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
-
the catalyzed anaplerotic reaction is very important replenishing oxaloacetate withdrawn from the tricarboxylic acid cycle for various pivotal biochemical pathways, overview
-
-
?
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
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
additional information
?
-
-
the transcarboxylase domain of pyruvate carboxylase is essential for assembly of the peroxisomal flavoenzyme alcohol oxidase
-
-
?
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
?
-
-
protein, but not the enzyme is essential for import and assembly of alcohol oxidase into peroxisomes
-
?
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
?
-
beta-cells possess compensatory systems that are activated in response to suppression of pyruvate carboxylase nzyme levels. The compensatory events include allosteric activation of pyruvate carboxylase due to increased levels of acetyl-CoA and enhanced conversion of isocitrate to 2-oxoglutarate and downstream metabolites via the cytosolic, NADP-dependent isocitrate dehydrogenase
-
-
?
additional information
?
-
-
starvation enhances pyruvate carboxylase activity, whereas diabetes also increases gluconeogenesis through enhanced uptake of substrate and increased flux through liver pyruvate carboxylase rats
-
-
?
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
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
enzyme activities of PC-(BC) and PC-(CT+BCCP) are not dependent on acetyl-CoA
-
ATP
-
at concentrations above saturating, MgATP2- activates bicarbonate-dependent ATP cleavage, but inhibits the overall reaction
biotin
-
activates through biotinylation of apoenzyme to holoenzyme
biotin
-
activates through biotinylation of apoenzyme to holoenzyme
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
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
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
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
K+
KCl
Mg2+
Mn2+
NH4+
Zinc
Co2+
-
divalent cation required, activates with 58% of the efficiency relative to Mg2+
KCl
-
optimal concentration: 0.175 mM, activates at lower concentrations, inhibits at higher concentrations
Mg2+
-
the presence of MgCl2 in excess of ATP produces a more than 3fold activation
Mg2+
the biotin carboxylase domain requires divalent cations for binding of the ATP substrate and for catalysis
Mg2+
-
divalent metal required, Mg2+, and with lower efficiency Mn2+ or Co2+
Mg2+
essential activator. Both acetyl-CoA and Mg2+ assist in coupling the MgATP-dependent carboxylation of biotin in the biotin carboxylase (BC) domain with pyruvate carboxylation in the carboxyl transferase (CT) domain. High Mg2+ concentration (above 7 mM) inhibits pyruvate carboxylation and MgATP cleavage but no inhibition of MgADP phosphorylation reaction
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+
-
3fold activation in presence of MnCl2 equimolar in concentration to ATP
Mn2+
-
divalent metal ion required, Mg2+ or Mn2+. Mn2+ inhibits at concentrations above 1.25 mM
Mn2+
-
divalent cation required, activates with 66% of the efficiency relative to Mg2+
Mn2+
-
each subunit contains one tightly bound metal ion, predominantly Mn2+, or mixtures of Mn2+ and Mg2+
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
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INHIBITOR
ORGANISM
UNIPROT
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-
cyclic di-3',5'-adenosine monophosphate
-
compound is bound at the dimer interface of the carboxyltransferase. domain. The aspartate pool in Lactococcus lactis is negatively regulated by cyclic di-3',5'-adenosine monophosphate, and high aspartate levels can be restored by expression of a cyclic di-3',5'-adenosine monophosphate enzyme. Mutations of residues in the binding site can abolish cyclic di-3',5'-adenosine monophosphate inhibition
KCl
-
activates at lower concentrations, inhibits at higher concentrations
Mercuric acetate
-
addition of Cys results in restoration of significant activity
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
-
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-
ATP
-
at concentrations above saturating, MgATP2- activates bicarbonate-dependent ATP cleavage, but inhibits the overall reaction
Avidin
-
100 molar excess amount completely inhibits after 5 min
-
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-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
L-Aspartate competitively inhibits hydrogencarbonate-dependent MgATP cleavage with respect to MgATP and also probably inhibits carboxybiotin formation and/or translocation of the carboxybiotin to the site of pyruvate carboxylation. Unlike acetyl-CoA, L-aspartate has no effect on the coupling between MgATP cleavage and oxaloacetate formation
Mg2+
-
when Mg2+ concentration in the assay exceeds that of ATP
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
Trinitrobenzenesulfonate
-
inactivation of acetyl-CoA dependent activity, no effect on activator-independent activity
Trinitrobenzenesulfonate
-
acetyl-CoA and adenosine 3',5'-diphosphate decrease the rate of loss of activity
Trinitrobenzenesulfonate
-
acetyl-CoA and adenosine 3',5'-diphosphate protect
additional information
-
L-Asp and 2-oxoglutarate occupy distinct regulatory sites on Aspergilus nidulans enzyme
-
additional information
-
no inhibitors: glutamate and alpha-ketoglutarate
-
additional information
-
insensitive to inhibition by di- and tricarboxylic acids
-
additional information
-
inhibition with physiological amounts of amino acids or dicarboxylate is not obtained
-
additional information
-
inhibition with physiological amounts of amino acids or dicarboxylate is not obtained
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
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
malonyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
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
oxamate
-
oxamate acts as a carboxyl acceptor, forming a carbamylated oxamate product and thereby accelerating the enzymatic decarboxylation reaction
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
acetyl CoA
-
enzyme activator, major effect is to promote the carboxylation of biotin, reduces the Kms for both MgATP2- and biotin, overview
acetyl-CoA
-
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
-
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
-
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
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
-
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
-
allosteric activator of pyruvate carboxylase, there is a 7fold increase in the turnover number for ATP cleavage induced by acetyl-CoA
acetyl-CoA
nonessential activator. Both acetyl-CoA and Mg2+ assist in coupling the MgATP-dependent carboxylation of biotin in the biotin carboxylase (BC) domain with pyruvate carboxylation in the carboxyl transferase (CT) domain. Absence of acetyl-CoA results in only 9% of fully activated enzyme. Acetyl-CoA also has a noticeable effect on the activity of the oxamate-induced decarboxylation of oxaloacetate but no effect on the rate of MgADP phosphorylation by carbamoyl phosphate
acetyl-CoA
acetyl-CoA acts to decrease the activation free energy of the reaction by both increasing the activation entropy and decreasing the activation enthalpy
acetyl-CoA
the substrates of the biotin carboxylase and carboxyl transferase domain are energetically coupled in the presence of acetyl-CoA. Both kinetic and energetic coupling between the two domains is lost in the absence of acetyl-CoA
acetyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanoyl-CoA, n-butanoyl-CoA, malonyl-CoA, CoA, acetoacetyl-CoA, oleoyl-CoA
acetyl-CoA
-
allosteric activator. Concentrations eliciting maximal activity are 0.013 mM, 0.042 mM and 0.084 mM at assay temperatures of 45°C, 55°C, and 65°C respectively
acyl-CoA derivatives
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
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
-
activity strongly influenced by the carbon source used for growth
-
additional information
-
starvation enhances pyruvate carboxylase activity. Pyruvate carboxylase and PEP carboxykinaseacts cooperatively
-
additional information
-
acetyl-CoA and K+ have no effect on ADP phosphorylation by carbamoyl phosphate
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.018
ATP
pH 7.5, 25°C, wild-type, 10 mM biotin, pyruvate carboxylation
0.04
ATP
pH 7.5, 25°C, mutant K119Q, 10 mM biotin, pyruvate carboxylation
0.054
ATP
pH 7.5, 25°C, mutant T882A, no biotin, pyruvate carboxylation
0.09
ATP
pH 7.5, 25°C, mutant T882A, 10 mM biotin, pyruvate carboxylation
0.2
ATP
-
37°C and 45°C, pH 8, Mg2+ concentration higher than ATP concentration
0.54 - 1.03
ATP
-
pH 8, 30°C, ATP-cleavage in absence of pyruvate
1.7
Carbamoyl phosphate
-
pH 7.8, 30°C, C249A mutant, with acetyl-CoA and K+
10.7
Carbamoyl phosphate
-
pH 7.8, 30°C, C249A mutant, without acetyl-CoA and K+
11.3
Carbamoyl phosphate
-
pH 7.8, 30°C, wild-type Pyc1, with acetyl-CoA and K+
12.3
Carbamoyl phosphate
-
pH 7.8, 30°C, wild-type Pyc1, without acetyl-CoA and K+
16
HCO3-
-
with saturating concentrations of the activator acetyl-CoA
0.15
pyruvate
5 mM Mg2+, pH 7.5, 25°C, wild-type, pyruvate carboxylation, Vmax: 3.98 micromol/mg/min
2.65
pyruvate
3 mM Mg2+, pH 7.5, 25°C, wild-type, pyruvate carboxylation, Vmax: 3.18 micromol/mg/min
3
pyruvate
1.5 mM Mg2+, pH 7.5, 25°C, wild-type, pyruvate carboxylation, Vmax: 1.41 micromol/mg/min
3.1
pyruvate
0.7 mM Mg2+, pH 7.5, 25°C, wild-type, pyruvate carboxylation, Vmax: 0.69 micromol/mg/min
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
-
additional information
additional information
0.5 mM Mg2+: Vmax (micromol/mg/min) 1.16, Ka (acetyl-CoA) 0.038 mM/1 mM Mg2+: Vmax (micromol/mg/min) 1.39, Ka (acetyl-CoA) 0.026 mM/1.5 mM Mg2+: Vmax (micromol/mg/min) 2.59, Ka (acetyl-CoA) 0.025 mM/3 mM Mg2+: Vmax (micromol/mg/min) 5.7, Ka (acetyl-CoA) 0.01 mM
-
additional information
additional information
-
0.5 mM Mg2+: Vmax (micromol/mg/min) 1.16, Ka (acetyl-CoA) 0.038 mM/1 mM Mg2+: Vmax (micromol/mg/min) 1.39, Ka (acetyl-CoA) 0.026 mM/1.5 mM Mg2+: Vmax (micromol/mg/min) 2.59, Ka (acetyl-CoA) 0.025 mM/3 mM Mg2+: Vmax (micromol/mg/min) 5.7, Ka (acetyl-CoA) 0.01 mM
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0013
ATP
pH 7.5, 25°C, mutant K119Q, no biotin, pyruvate carboxylation
0.04
ATP
pH 7.5, 25°C, mutant K119Q, 10 mM biotin, pyruvate carboxylation
0.6
ATP
pH 7.5, 25°C, mutant T882A, 10 mM biotin, pyruvate carboxylation
0.043
Carbamoyl phosphate
-
pH 7.8, 30°C, C249A mutant, with acetyl-CoA and K+
0.11
Carbamoyl phosphate
-
pH 7.8, 30°C, wild-type Pyc1, with acetyl-CoA and K+
0.11
Carbamoyl phosphate
-
pH 7.8, 30°C, wild-type Pyc1, without acetyl-CoA and K+
0.13
Carbamoyl phosphate
-
pH 7.8, 30°C, C249A mutant, without acetyl-CoA and K+
0.1
oxaloacetate
co-substrate: ADP + phosphate, mutant H216N, oxaloacetate decarboxylation, pH 7.8, 30°C
0.28
oxaloacetate
co-substrate: ADP + phosphate, wild-type, oxaloacetate decarboxylation, pH 7.8, 30°C
0.052
pyruvate
co-substrate: HCO3-, mutant H216N, pyruvate carboxylation, pH 7.8, 30°C
2.71
pyruvate
mutant E1027R, pH 7.8, 30°C, Hill coefficient 2.3, presence of acetyl-CoA
6.05
pyruvate
mutant R469K, pH 7.8, 30°C, Hill coefficient 0.9, presence of acetyl-CoA
11
pyruvate
co-substrate: HCO3-, wild-type, pyruvate carboxylation, pH 7.8, 30°C
11.3
pyruvate
mutant R469S, pH 7.8, 30°C, Hill coefficient 2.3, presence of acetyl-CoA
12.3
pyruvate
mutant D1018A, pH 7.8, 30°C, Hill coefficient 2.1, presence of acetyl-CoA
14.9
pyruvate
mutant E1027A, pH 7.8, 30°C, Hill coefficient 3.0, presence of acetyl-CoA
17.6
pyruvate
wild-type, pH 7.8, 30°C, Hill coefficient 2.7, presence of acetyl-CoA
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
ATP
pH 7.5, 25°C, mutant K119Q, no biotin, pyruvate carboxylation
1.125
ATP
pH 7.5, 25°C, mutant K119Q, 10 mM biotin, pyruvate carboxylation
7.16
ATP
pH 7.5, 25°C, mutant T882A, 10 mM biotin, pyruvate carboxylation
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
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
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
0.49
-
cell extract, expressed in NZN111 after aerobic growth and induction with IPTG
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
additional information
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
0.17
-
cell extract, expressed in AFP111 after growth under H2-atmosphere and induction with IPTG
0.17
-
cell extract, expressed in NZN111 after aerobic growth without IPTG induction
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.1
7.5
7.6
7.8
8 - 8.5
8.5
7.8
-
assay at, carboxylation of free biotin, ATP cleavage, and ADP phosphorylation by carbamoyl phosphate
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
30
-
assay at, carboxylation of free biotin, ATP cleavage, and ADP phosphorylation by carbamoyl phosphate
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
wild-type strain PAO1, genes pycA and pycB ecoding pyruvate carboxylase subunits PycA and PycB
-
-
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
-
brenda
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
brenda
-
enzyme activity is preserved in the islets of obese animals, but it is reduced in the islets of animal models of type 2 diabetes
brenda
additional information
-
tissue-specific expression. In dairy cows, the expression of the enzyme is markedly elevated during the transition from calving to lactation
brenda
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
brenda
additional information
-
tissue-specific expression, production of specific forms of PC mRNA are linked to certain physiological states, i.e. development, gluconeogenesis and lipogenesis
brenda
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
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
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
-
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
-
metabolism
-
the PYC-catalyzed carboxylation of pyruvate is the predominant reaction leading to oxaloacetate in Listeria monocytogenes
metabolism
-
simultaneous overexpression of isocitrate dehydrogenase (IDP1) and pyruvate carboxylase (PYC) gene PYC1 increase the amount of secreted alpha-ketoglutaric acid. About 19% more alpha-ketoglutaric acid in comparison with the control strain H355 are produced in bioreactor with raw glycerol as carbon source resulting in the highest yield of accumulated alpha-ketoglutaric acid of about 186 g/L after 117 h of cultivation
metabolism
-
the PYC-catalyzed carboxylation of pyruvate is the predominant reaction leading to oxaloacetate in Listeria monocytogenes
-
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
physiological function
-
pyruvate carboxylase protein is required for import and assembly of the peroxisomal enzyme alcohol oxidase
physiological function
-
a gene deletion mutant shows similar morphologies to those of the wild-typewhen succinate is supplied as the carbon source. When glucose or pyruvate is provided as the carbon source, the mutation prevents growth. In the colony morphology assay, the wild type initially produces a smooth colony, which forms wrinkle structures in the centre starting on day 3. The deletion mutant and K572A colonies begin to wrinkle on day 2 and exhibit a flatter morphology with several exaggerated wrinkles in a spoke formation
physiological function
a gene disruption strain is auxotrohp for biotin due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Catalytically active Pyc is required and can be supported by Mycobacterium tuberculosis Pyc
physiological function
-
a gene disruption strain is auxotrohp for biotin due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Catalytically active Pyc is required and can be supported by Mycobacterium tuberculosis Pyc
-
Show AA Sequence and Transmembrane Helices (17340 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
120000
125000
128000
130000
50000
500000
54000
55000
60000
Leptosphaeria michotii
-
4 * 60000, biotin containing alpha-subunit, + 4 * 50000, biotin-free beta-subunit
65000
70000
additional information
-
at high enzyme concentration the enzyme aggregates to form high molecular weight aggregates
50000
Leptosphaeria michotii
-
4 * 60000, biotin containing alpha-subunit, + 4 * 50000, biotin-free beta-subunit
54000
-
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
55000
-
alpha4,beta4, 4 * 55000 + 4 * 65000, the 65000 Da subunit is biotinylated, the 55000 Da subunit is not, SDS-PAGE
55000
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
65000
-
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
65000
-
alpha4,beta4, 4 * 55000 + 4 * 65000, the 65000 Da subunit is biotinylated, the 55000 Da subunit is not, SDS-PAGE
70000
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homotetramer
monomer
octamer
polymer
-
about 4% of the total enzyme elutes as a high molecular weight species, gel filtration
tetramer
additional information
?
-
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
dimer
-
PC-(BC) exists as a monomer and as a dimer, (CT+BCCP) exists mostly as a dimer, gel filtration
monomer
-
PC-(BC) exists as a monomer and as a dimer, gel filtration
octamer
Leptosphaeria michotii
-
4 * 60000, biotin containing alpha-subunit, + 4 * 50000, biotin-free beta-subunit
octamer
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
octamer
-
alpha4,beta4, 4 * 55000 + 4 * 65000, the 65000 Da subunit is biotinylated, the 55000 Da subunit is not, SDS-PAGE
octamer
Methanococcus sp.
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
octamer
-
4 * 55000, about, alpha-subunit, + 4 * 70000, about, beta-subunit
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 * 128500-137000, SDS-PAGE, gel filtration, intact enzyme
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
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
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
-
all three functional domains, biotin carboxylase, carboxytransferase and biotin carboxyl carrier protein, are located on a single polypeptide chain, domain structures, 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
localization of a BCCP domain is located in the active site of the carboxytransferase domain that participates in the carboxyltransfer reaction
additional information
-
localization of a BCCP domain is located in the active site of the carboxytransferase domain that participates in the carboxyltransfer reaction
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
Methanococcus sp.
-
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
-
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
-
each protomer consists of two polypeptide chains, with alpha and beta subunits arranged in an (alphabeta)4 structure
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
-
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
localization of a BCCP domain is located in the active site of the carboxytransferase domain that participates in the carboxyltransfer reaction
additional information
-
localization of a BCCP domain is located in the active site of the carboxytransferase domain that participates in the carboxyltransfer reaction
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
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
C-terminal region, and wild-type and F1077A mutant enzymes, microseeding, room temprarture, sitting drop method using a reservoir solution containing 0.8% w/v PEG 3350 and 90 mM MnCl for the wild-type and 15% w/v PEG 3350 and 200 mM ammonium tartrate for the mutant, X-ray diffraction structure determination and analysis at 2.8 A resolution
crystal structures of biotin carboxylase domain deletion mutant and of mutant K419A/E421A/E422A reveal an alpha2beta4 stoichiometry
complete structure of pyruvate carboxylase at 2.0 A resolution, domain architecture of pyruvate carboxylase
-
crystal structures of mutant T882A pyruvate carboxylase are determined cocrystallized with phosphonoacetate and MgADP
structure of the carboxyltransferase domain, to 2.26-2.4 A resolution. Oxamate is positioned in the active site in an identical manner to the substrate, pyruvate
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
pyruvate carboxylase tetramers map asymmetric and symmetric architectures, which are coupled to the consecutive biotin carboxylase and carboxyltransferase enzymatic reactions respectively. The catalytic activity occurs one layer at a time
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
A610T
M743I
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
R451C
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant enzyme shows markedly decreased acetyl-CoA-dependent activation
V145A
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A
G746A
-
mutation to corresponding Entercoccus faecalis residue. Mutant shows similar activity as wild-type, mutation reduces inhibition by cyclic di-3',5'-adenosine monophosphate to 40%, compared to 60% for wild-type
Y715T
-
mutation to correspoinding human residue. Mutant shows similar activity as wild-type, mutation abolishes inhibition by cyclic di-3',5'-adenosine monophosphate
A465R
mutation in the alpha subunit, abolishes the formation of the holoenzyme, catalytically inactive
D502A/E507A
mutation in the alpha subunit, mutant forms a stable holoenzyme, about 40% of wild-type activity
H476A/E478A
mutation in the alpha subunit, mutant forms a stable holoenzyme and is fully active
H476A/E478A/D502A/E507A
mutation in the alpha subunit, abolishes the formation of the holoenzyme, catalytically inactive
K419A/E421A/E422A
mutations bin the beta subunit designed to reduce the surface entropy. The mutations have no effect on the catalytic activity of the enzyme
Q452stop
mutation in the alpha subunit, abolishes the formation of the holoenzyme
R401E
mutation in the alpha subunit, mutant forms a stable holoenzyme, about 50% of wild-type activity
A465R
Methylobacillus flagellatus DSM 6875
-
mutation in the alpha subunit, abolishes the formation of the holoenzyme, catalytically inactive
-
H476A/E478A
Methylobacillus flagellatus DSM 6875
-
mutation in the alpha subunit, mutant forms a stable holoenzyme and is fully active
-
K419A/E421A/E422A
Methylobacillus flagellatus DSM 6875
-
mutations bin the beta subunit designed to reduce the surface entropy. The mutations have no effect on the catalytic activity of the enzyme
-
Q452stop
Methylobacillus flagellatus DSM 6875
-
mutation in the alpha subunit, abolishes the formation of the holoenzyme
-
R401E
Methylobacillus flagellatus DSM 6875
-
mutation in the alpha subunit, mutant forms a stable holoenzyme, about 50% of wild-type activity
-
Y542V/A557Q/S762D
-
the triple mutation fully inactivates the moonlighting function of Pyc1, but not the enzyme activity of pyruvate carboxylase
A55T
-
mutation in the beta subunit, reduces activity by 50fold and interferes with biotin binding to the active site,mutant exhibits growth on pyruvate similar to the wild type
K572A
-
mutation in the beta subunit, abolishes biotinylation and leads to growth defects in pyruvate that are similar to that of a gene deletion mutant
D1018A
mutant has increased activity in the absence of acetyl-CoA, but not in its presence
D420A
mutation affects acetyl-CoA binding, enhances the activity of the enzyme in the absence of acetyl-CoA
E1027A
mutant has increased activity in the absence of acetyl-CoA, but not in its presence
E1027R
mutant has increased activity in the absence of acetyl-CoA, but not in its presence
H216N
no differences to quarterny structures compared to wild-type. Mutation results in a 9fold increase in the Km for MgATP in its steady-state cleavage in the absence of pyruvate and a 3fold increase in the Km for MgADP in its steady-state phosphorylation by carbamoyl phosphate. kcat/Km (MgATP)98% decreased compared to wild-type. For MgADP phosphorylation kcat/Km is 99.5% decreased compared to wild-type. The Kd of the enzyme MgATP complex is essentially the same in the wildtype enzyme and H216N but the first-order rate constant for MgATP cleavage in the single-turnover experiments in H216N is only 0.75% of that for the wild-type enzyme, and thus, the MgATP cleavage step is rate-limiting in the steady state for H216N but not for the wild-type enzyme
K1119Q
mutant that lacks tethered biotin. Addition of 10 mM biotin increases the kcat of MgATP hydrolysis to rates observed for wild-type RePC in the absence of free biotin. This rate increase, coupled with a 35fold decrease in the Km for MgATP, results in a nearly 1000fold increase in the catalytic efficiency of the mutant K1119Q RePC catalyzed reaction when 10 mM free biotin is added
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
R424
mutation affects acetyl-CoA binding, enhances the activity of the enzyme in the absence of acetyl-CoA. Mutation decreases the activation enthalpy of the pyruvate carboxylation reaction by an amount consistent with removal of a single hydrogen bond
R427K
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 76fold higher compared to wild-type, kcat 32% of wild-type enzyme, Km (MgATP) 2.6fold higher compared to wild-type, kcat/Km value 12% of wild-type. Ka (activation value) for Mg2+ is 8fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.4% of wild-type in the presence of acetyl-CoA/0.8% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 21% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 6% biotin carboxylation rate of wild-type. residual activity at saturating concentrations of L-aspartate is 2fold greater than wild-type
R427S
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 15fold higher compared to wild-type, kcat 41% of wild-type enzyme, Km (MgATP) 1.5fold higher compared to wild-type, kcat/Km value 26% of wild-type. Ka (activation value) for Mg2+ is 2fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 1.1% of wild-type in the presence of acetyl-CoA/5.8% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 17% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity similar to wild-type. Mutant exhibits 6% biotin carboxylation rate of wild-type
R429S
residue Arg429 is especially important for acetyl CoA binding. Mutation results in a 100fold increase in the Ka of acetyl-CoA activation and a large decrease in the cooperativity of this activation
R469K
mutant shows increased enzymic activity in the presence and absence of acetyl-CoA
R469S
mutant shows increased enzymic activity in the presence and absence of acetyl-CoA
R472K
45% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 252fold higher compared to wild-type, kcat 32% of wild-type enzyme, Km (MgATP) 6.7fold higher compared to wild-type, kcat/Km value 3% of wild-type. Ka (activation value) for Mg2+ is 37fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.6% of wild-tpye in the presence of acetyl-CoA/0.9% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 8% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 3% biotin carboxylation rate of wild-type
R472S
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
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
D420A
Rhizobium etli ATCC 51251
-
mutation affects acetyl-CoA binding, enhances the activity of the enzyme in the absence of acetyl-CoA
-
E1027A
Rhizobium etli ATCC 51251
-
mutant has increased activity in the absence of acetyl-CoA, but not in its presence
-
E1027R
Rhizobium etli ATCC 51251
-
mutant has increased activity in the absence of acetyl-CoA, but not in its presence
-
R424
Rhizobium etli ATCC 51251
-
mutation affects acetyl-CoA binding, enhances the activity of the enzyme in the absence of acetyl-CoA. Mutation decreases the activation enthalpy of the pyruvate carboxylation reaction by an amount consistent with removal of a single hydrogen bond
-
R429K
Rhizobium etli ATCC 51251
-
enhances the activity of the enzyme in the absence of acetyl-CoA
-
R429S
Rhizobium etli ATCC 51251
-
residue Arg429 is especially important for acetyl CoA binding. Mutation results in a 100fold increase in the Ka of acetyl-CoA activation and a large decrease in the cooperativity of this activation
-
R469K
Rhizobium etli ATCC 51251
-
mutant shows increased enzymic activity in the presence and absence of acetyl-CoA
-
R469S
Rhizobium etli ATCC 51251
-
mutant shows increased enzymic activity in the presence and absence of acetyl-CoA
-
H216N
-
no differences to quarterny structures compared to wild-type. Mutation results in a 9fold increase in the Km for MgATP in its steady-state cleavage in the absence of pyruvate and a 3fold increase in the Km for MgADP in its steady-state phosphorylation by carbamoyl phosphate. kcat/Km (MgATP)98% decreased compared to wild-type. For MgADP phosphorylation kcat/Km is 99.5% decreased compared to wild-type. The Kd of the enzyme MgATP complex is essentially the same in the wildtype enzyme and H216N but the first-order rate constant for MgATP cleavage in the single-turnover experiments in H216N is only 0.75% of that for the wild-type enzyme, and thus, the MgATP cleavage step is rate-limiting in the steady state for H216N but not for the wild-type enzyme
-
K1119Q
-
mutant that lacks tethered biotin. Addition of 10 mM biotin increases the kcat of MgATP hydrolysis to rates observed for wild-type RePC in the absence of free biotin. This rate increase, coupled with a 35fold decrease in the Km for MgATP, results in a nearly 1000fold increase in the catalytic efficiency of the mutant K1119Q RePC catalyzed reaction when 10 mM free biotin is added
-
R427K
-
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 76fold higher compared to wild-type, kcat 32% of wild-type enzyme, Km (MgATP) 2.6fold higher compared to wild-type, kcat/Km value 12% of wild-type. Ka (activation value) for Mg2+ is 8fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.4% of wild-type in the presence of acetyl-CoA/0.8% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 21% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 6% biotin carboxylation rate of wild-type. residual activity at saturating concentrations of L-aspartate is 2fold greater than wild-type
-
R427S
-
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 15fold higher compared to wild-type, kcat 41% of wild-type enzyme, Km (MgATP) 1.5fold higher compared to wild-type, kcat/Km value 26% of wild-type. Ka (activation value) for Mg2+ is 2fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 1.1% of wild-type in the presence of acetyl-CoA/5.8% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 17% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity similar to wild-type. Mutant exhibits 6% biotin carboxylation rate of wild-type
-
R472K
-
45% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 252fold higher compared to wild-type, kcat 32% of wild-type enzyme, Km (MgATP) 6.7fold higher compared to wild-type, kcat/Km value 3% of wild-type. Ka (activation value) for Mg2+ is 37fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.6% of wild-tpye in the presence of acetyl-CoA/0.9% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 8% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 3% biotin carboxylation rate of wild-type
-
R472S
-
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 203fold higher compared to wild-type, kcat 25% of wild-type enzyme, Km (MgATP) 8.7fold higher compared to wild-type, kcat/Km value 2% of wild-type. Ka (activation value) for Mg2+ is 30fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.6% of wild-type in the presence of acetyl-CoA/1.2% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 5% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 2% biotin carboxylation rate of wild-type
-
T882A
-
T882 mutant is a tetrameric holoenzyme where positioning of the tethered biotin favors placement in the BC domain. Free biotin increases the kcat for both the wild-type and the T882A mutant RePC-catalyzed reactions without having a major effect on the Km for MgATP. Crystal structures of mutant T882A pyruvate carboxylase are determined cocrystallized with phosphonoacetate and MgADP
-
E40R
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
E433R
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
R36E
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
R36E/E433R
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
A610T
-
naturally occurring mutation involved in pyruvate carboxylase deficiency type A, the mutant's catalytic activity and steady-state level are markedly decreased
R472S
-
the mutation severely decreases the affinity of the enzyme for acetyl-CoA
R472S
more than 70% of mutant exist in the tetrameric form, Ka (activation value) for acetyl-CoA is 203fold higher compared to wild-type, kcat 25% of wild-type enzyme, Km (MgATP) 8.7fold higher compared to wild-type, kcat/Km value 2% of wild-type. Ka (activation value) for Mg2+ is 30fold higher compared to wild-type. Bicarbonate-dependent ATP cleavage activity: 0.6% of wild-type in the presence of acetyl-CoA/1.2% of wild-type in the absence of acetyl-CoA. ADP phosphorylation by carbamoyl phosphate: 5% of wild-type in the presence of acetyl-CoA. In the absence of acetyl-CoA activity slightly increased compared to wild-type. Mutant exhibits 2% biotin carboxylation rate of wild-type
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
T882A
T882 mutant is a tetrameric holoenzyme where positioning of the tethered biotin favors placement in the BC domain. Free biotin increases the kcat for both the wild-type and the T882A mutant RePC-catalyzed reactions without having a major effect on the Km for MgATP. Crystal structures of mutant T882A pyruvate carboxylase are determined cocrystallized with phosphonoacetate and MgADP
additional information
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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
additional information
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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
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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
additional information
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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
additional information
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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
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transgenic mice carrying a dominant-negative mutant CREB show a global reduction of gluconeogenic enzymes including PC, PEPCK and glucose 6-phosphatase
additional information
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deletion of the PC gene in this yeast impairs alcohol oxidase activity, causing the accumulation of inactive alcohol oxidase in the cytosol
additional information
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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
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overexpression of v-MAFA in INS1 cells causes a 5fold increase of pyruvate carboxylase mRNA
additional information
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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
additional information
construction of deletion mutants lacking the biotin carboxylase domain or both biotin carboxylase and biotin carboxyl carrier domains. The biotin carboxyl carrier domain devoid of biotin does not contribute directly to the enzymatic reaction, a deletion mutant demonstrates biotin-independent oxaloacetate decarboxylation activity
additional information
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construction of deletion mutants lacking the biotin carboxylase domain or both biotin carboxylase and biotin carboxyl carrier domains. The biotin carboxyl carrier domain devoid of biotin does not contribute directly to the enzymatic reaction, a deletion mutant demonstrates biotin-independent oxaloacetate decarboxylation activity
additional information
generation of functional, mixed hybrid tetramers using the E218A (inactive biotin carboxylase domain) and T882S (low pyruvate binding, low activity) mutant forms of pyruvate carboxylase. The apparent Ka pyruvate for the pyruvate-stimulated release of Pi by the hybrid tetramer is comparable to the wild-type enzyme and nearly 10fold lower than that for the T882S homotetramer. The ratio of the rates of oxaloacetate formation to Pi release for the WT:T882S[1:1] complex and 218A:T882S[1:1] hybrid tetramer-catalyzed reactions is 0.5 and 0.6, respectively, while the T882S homotetramer exhibits a near 1:1 coupling of the two domains
additional information
Rhizobium etli ATCC 51251
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construction of deletion mutants lacking the biotin carboxylase domain or both biotin carboxylase and biotin carboxyl carrier domains. The biotin carboxyl carrier domain devoid of biotin does not contribute directly to the enzymatic reaction, a deletion mutant demonstrates biotin-independent oxaloacetate decarboxylation activity
-
additional information
Rhizobium etli ATCC 51251
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generation of functional, mixed hybrid tetramers using the E218A (inactive biotin carboxylase domain) and T882S (low pyruvate binding, low activity) mutant forms of pyruvate carboxylase. The apparent Ka pyruvate for the pyruvate-stimulated release of Pi by the hybrid tetramer is comparable to the wild-type enzyme and nearly 10fold lower than that for the T882S homotetramer. The ratio of the rates of oxaloacetate formation to Pi release for the WT:T882S[1:1] complex and 218A:T882S[1:1] hybrid tetramer-catalyzed reactions is 0.5 and 0.6, respectively, while the T882S homotetramer exhibits a near 1:1 coupling of the two domains
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additional information
construction of chimeric enzymes of Pyc1 and Pyc2
additional information
construction of chimeric enzymes of Pyc1 and Pyc2
additional information
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construction of chimeric enzymes of Pyc1 and Pyc2
additional information
-
50% down-regulation of the enzyme in the RTG1 and the RTG2 mutants
additional information
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construction of chimeric enzymes of Pyc1 and Pyc2
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
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
45
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
80
-
rapid inactivation, t1/2: 1 h in 100 mM Tris/HCl, pH 7, sulfate salts provide partial protection
additional information
additional information
-
Tris hydrochloride, KCl or a mixture of MgCl2 and ATP protects against heat inactivation
additional information
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acetyl-CoA protects against thermal inactivation
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA and sodium pyruvate protects against cold inactivation. L-Asp decreases inactivation, 1 M sucrose gives complete protection
-
acetyl-CoA stabilizes quarternary structure of the enzyme
dilution results in irreversible inactivation, which can be partially avoided by addition of acetyl-CoA. Glycerol stabilizes
-
does not participate directly in the reaction mechanism, but may play a structural role essential to the integrity of the enzymes tetrameric structure
-
inactivated reversibly and converted to protomers by incubation at 0°C in the presence of high concentrations of Cl- salts of monovalent cations. MgCl2 or sucrose prevent inactivation
-
the presence of KCl at 10, 20, 50, and 100 mM potassium phosphate buffer-KCl buffer at 0°C leads to 85%, 44%, 17% and 0% loss of activity
-
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.
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 90% activity after 1 month in the presence of 10% inositol, 30% loss of activity after 24 h without inositol
-
0°C, 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
-
4°C, 90% activity after 1 month in the presence of 10% inositol, 30% loss of activity after 24 h without inositol
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partial
recombinant His9-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 by affinity chromatography
-
using Ni-NTA chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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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
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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
DNA and amino acid sequence determination and analysis
DNA and amino acid sequence determination and analysis, expression mutant enzymes and of the isolated biotin carboxylase domain
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DNA and amino acid sequence determination and analysis, genetic structure, key cognate transcription factors regulating tissue-specific expression, transcriptional regulation, 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
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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
expressed in Escherichia coli and Streptomyces lividans as a His-tagged fusion protein. In Streptomyces lividans a functional His-EhPYC1 is expressed
expressed in Escherichia coli as a His-tagged fusion protein
expression analysis of the enzyme in diverse wild-type and knockout insulinoma cell lines, overview
expression in Escherichia coli GJT001, coexpression with pantothenate kinase
-
expression in Escherichia coli JM109
expression of His9-tagged wild-type and mutant enzymes in Escherichia coli strain BL21
-
expression of the C-terminal region, excluding the mitochondrial targeting sequence, in Escherichia coli strain BL21(DE3)
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
-
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
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
-
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
-
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, genetic structure, key cognate transcription factors regulating tissue-specific expression, transcriptional regulation, overview
-
DNA and amino acid sequence determination and analysis, genetic structure, key cognate transcription factors regulating tissue-specific expression, transcriptional regulation, overview
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of pyruvate carboxylase is be increased 2-5fold at the onset of obesity in Zucker fatty rats
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
medicine
synthesis
biotechnology
-
coexpression of recombinant pyruvate coarboxylase in BHK-21 cells improves the production of human erythropoietin in a continuously perfused bioreactor
biotechnology
FLAG-tagged human pyruvate carboxylase is introduced into a dihydrofolate-deficient CHO cell line DG44. Through the expression of the human pyruvate carboxylase enzyme, lactate formation in CHO cell culture can be efficiently reduced. This effect of expression of the human pyruvate carboxylase is observed not only in adherent batch culture using the serum-containing medium but in the serum-free suspension fed-batch culture as well, demonstrating its potential use to extend the culture longevity of CHO cell culture, which often shows a significant accumulation of lactate
medicine
-
A610T mtation leads to type A pyruvate carboxylase deficiency, no import of the enzyme into mitochondria
medicine
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
-
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
-
in lung tumor tissue, pyruvate carboxylase shows increased levels of protein and mRNA
medicine
-
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
-
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
medicine
-
induction of pyruvate decarboxylase during chronic suppression of glutamine metabolism is a mechanism of resistance to therapies targeting glutaminolysis
medicine
cancerous tissues of patients with early-stage non-small-cell lung cancer display enhanced pyruvate carboxylase activity. Pyruvate carboxylase overexpression is found in cancer cells rather than in stromal cells of tumor tissues. Pyruvate carboxylase knockdown induces multinucleation, decreases cell proliferation and colony formation in human non-small-cell lung cancer cells, and reduces tumor growth in a mouse xenograft model
medicine
pyruvate carboxylase is expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. There is a statistical association between the levels of pyruvate carboxylase expression and tumor size and tumor stage. The abundance of both pyruvate carboxylase mRNA and protein in MDA-MB-231 and MDA-MB-435 cells is 2-3fold higher than that in MCF-7 and SKBR-3 cells. siRNA-mediated knockdown of expression in MDA-MB-231 and MDA-MB-435 cells results in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of pyruvate carboxylase in MCF-7 cells results in a 2fold increase in their proliferation rate, migration and invasion abilities
synthesis
-
super-transfection of CHO cells with a mammalian construct bearing codon optimized yeast cytosolic pyruvate carboxylase PYC2 and a strong fusion promoter for optimal expression of PYC2 enzyme in order to control the lactate metabolism of mAb (IgG1-kappa) producing CHO clones. Presence of Pyc2 results in an improved mAb titer up to 5%, galactosylation up to 2.5folds, and mannosylation up to twofold
synthesis
-
the presence of 10 mM L-aspartate in the production medium directly represses pyruvate carboxylase expression. This leads to limited malate flux which in turn regulates the malate/citrate antiporters resulting in increasing cis-aconitate decarboxylase activity to simultaneously convert cis-aconitate, citrate isomer, into itaconic acid
synthesis
-
the presence of 10 mM L-aspartate in the production medium directly represses pyruvate carboxylase expression. This leads to limited malate flux which in turn regulates the malate/citrate antiporters resulting in increasing cis-aconitate decarboxylase activity to simultaneously convert cis-aconitate, citrate isomer, into itaconic acid
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Release 2023.1 (January 2023)
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