Information on EC 6.4.1.1 - pyruvate carboxylase

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

EC NUMBER
COMMENTARY hide
6.4.1.1
-
RECOMMENDED NAME
GeneOntology No.
pyruvate carboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate + HCO3- = ADP + phosphate + oxaloacetate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxylation
-
-
-
-
cleavage of C-N-linkage
hydrolysis of peptide bond
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
anapleurotic synthesis of oxalacetate
-
-
Carbon fixation pathways in prokaryotes
-
-
Citrate cycle (TCA cycle)
-
-
gluconeogenesis II (Methanobacterium thermoautotrophicum)
-
-
gluconeogenesis III
-
-
incomplete reductive TCA cycle
-
-
itaconate biosynthesis
-
-
Metabolic pathways
-
-
Methanobacterium thermoautotrophicum biosynthetic metabolism
-
-
Microbial metabolism in diverse environments
-
-
Pyruvate metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
pyruvate:carbon-dioxide ligase (ADP-forming)
A biotinyl-protein containing manganese (animal tissues) or zinc (yeast). The animal enzyme requires acetyl-CoA.
CAS REGISTRY NUMBER
COMMENTARY hide
9014-19-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
thermophilic
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Leptosphaeria michotii
-
-
-
Manually annotated by BRENDA team
Listeria monocytogenes Sv1/2a EGD-e
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Methanococcus sp.
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicum
Methanothermobacter thermautotrophicum DELTAH
strain DELTAH
-
-
Manually annotated by BRENDA team
ass3
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain P4 (soil-isolate)
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
overexpressing strain
-
-
Manually annotated by BRENDA team
strain DM18
SwissProt
Manually annotated by BRENDA team
Rm1021
-
-
Manually annotated by BRENDA team
Rm1021
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
A2
-
-
Manually annotated by BRENDA team
A2
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + carbamoyl phosphate
ATP + ?
show the reaction diagram
ADP + carbamoylphosphate
?
show the reaction diagram
ATP + oxamate + HCO3- + H+
ADP + phosphate + ?
show the reaction diagram
-
-
-
-
?
ATP + pyruvate + HCO3-
?
show the reaction diagram
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
ATP + pyruvate + HCO3- + H+
ADP + oxaloacetate + phosphate
show the reaction diagram
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + pyruvate + HCO3-
?
show the reaction diagram
ATP + pyruvate + HCO3-
ADP + oxaloacetate + phosphate
show the reaction diagram
ATP + pyruvate + HCO3-
ADP + phosphate + oxaloacetate
show the reaction diagram
ATP + pyruvate + HCO3- + H+
ADP + phosphate + oxaloacetate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
enzyme activities of PC-(BC) and PC-(CT+BCCP) are not dependent on acetyl-CoA
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cs+
-
monovalent cation required, order of efficiency: Rb+, K+, Cs+/ NH4+
MnCl2
-
7.5 mM, can partially replace MgCl2
Rb+
-
monovalent cation required, Rb+ is most effective
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
inactivation follows pseudo-first-order kinetics, the rate of inactivation is greater at low enzyme concentrations
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate
-
inhibitor with respect to MgATP2-
2-oxoadipate
-
-
2-oxoglutarate
4-Acetamido-4'-(iodoacetyl)-aminostilbene-2,2'-disulfonic acid
-
-
acetyl-CoA
-
0.1 mM
Avidin
CTP
-
in presence of ATP
Formycin A 5'-triphosphate
-
-
GTP
-
in presence of ATP
Hydroxypyruvate
-
-
iodoacetate
-
-
KCl
-
activates at lower concentrations, inhibits at higher concentrations
L-Asn
-
-
L-aspartate
L-cystine
-
-
L-Glu
-
-
L-glutamate
Mercuric acetate
-
addition of Cys results in restoration of significant activity
Methanesulfonyl-CoA
methylphosphonate
-
-
MgATP2-
-
substrate inhibition
N-(7-Dimethylamino-4-methyl-3-coumarinyl)maleimide
-
-
NaCl
-
slight inhibition at 20 mM
o-phthalaldehyde
-
-
oxaloacetate
Oxamate
p-hydroxymercuribenzoate
-
-
phenylacetate
phenylacetic acid
phenylmercuric acetate
-
-
phosphate
-
-
Phosphonoacetate
-
-
pyruvate
-
substrate inhibition
Sodium benzoate
-
-
sulfhydryl reagents
-
effects of ATP, acetyl-CoA, and oxalacetate on the rates of inactivation of pyruvate carboxylase by sulfhydryl reagents depend upon the anion present, the reagent used, and the phase of inactivation considered. Protection by acetyl-CoA is cooperative
TNFalpha
-
pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
Trinitrobenzenesulfonate
UTP
-
in presence of ATP
Zn2+
Methanothermobacter thermautotrophicum
-
in presence of Mg2+
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate
-
allosteric activator of pyruvate carboxylase. The increase in activity between 2 mM and saturating MgATP is approximately 16fold
acetoacetyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
acetyl CoA
acetyl-CoA
acyl-CoA derivatives
biotin
-
-
Butyryl-CoA
-
can replace acetyl-CoA with little efficiency
L-aspartate
-
allosteric activator
Lactate
-
activates
malonyl-CoA
-
activation in decreasing order: acetyl-CoA, n-propanyl-CoA, n-butanoyl-CoA, malonyl-CoA/ CoA, acetoacetyl-CoA, oleoyl-CoA
Methanesulfonyl-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
palmitoyl-CoA
-
activated by long-chain acyl-CoA derivatives
propionyl-CoA
TNFalpha
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pyruvate decarboxylase activity decreases in TNFalpha-sensitive cells but increases in bcl-2 transfected cells
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028 - 2
ADP
0.009 - 9.2
ATP
3.3 - 18
biotin
1.7 - 12.3
Carbamoyl phosphate
0.22 - 400
HCO3-
0.027 - 1.8
MgATP2-
4.1
Oxamate
-
ATPase reaction, wild-type, pH 7.5, 25C
0.039 - 16.2
pyruvate
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.013
ADP
Rhizobium etli
-
pH 7.5, 25C, wild-type, reverse reaction
0.0013 - 60
ATP
0.043 - 0.13
Carbamoyl phosphate
11.6 - 60
HCO3-
0.056 - 0.28
oxaloacetate
0.052 - 60
pyruvate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.11 - 589
ADP
0.0011 - 99
ATP
1.08
HCO3-
Rhizobium etli
-
pH 7.5, 25C, wild-type, pyruvate carboxylation
195
0.7 - 48.3
pyruvate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.89
ADP
-
80C, pH 8.5
2.24 - 5.34
ATP
4.5 - 5
L-aspartate
0.4 - 0.5
MgATP2-
0.22
oxaloacetate
-
pH 8
8 - 19
Oxamate
10
pyruvate
-
ATPase reaction, wild-type, pH 7.5, 25C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6
L-Malate
Emiliania huxleyi
B9X0T8
pH 8, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
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
0.008
-
cells grown on a phosphate-deficient medium TRP, a coupled assay with malate dehydrogenase
0.03
-
cells grown on a phosphate-sufficient minimal medium M9, a coupled assay with malate dehydrogenase
0.05
-
cell extract, expressed in NZN111 after growth under CO2-atmosphere without IPTG induction
0.056
-
cell extract, expressed in AFP111 after growth under CO2-atmosphere without IPTG induction
0.068
-
cell extract, expressed in NZN111 after growth under CO2-atmosphere and induction with IPTG
0.12
-
cell extract, expressed in AFP111 after growth under CO2-atmosphere and induction with IPTG
0.17
-
cell extract, expressed in AFP111 after growth under H2-atmosphere and induction with IPTG; cell extract, expressed in NZN111 after aerobic growth without IPTG induction
0.49
-
cell extract, expressed in NZN111 after aerobic growth and induction with IPTG
0.587
-
control CHO-K1 cells
0.72
-
cell extract, expressed in AFP111 after aerobic growth and induction with IPTG
0.81
-
cell extract, expressed in AFP111 after aerobic growth without IPTG induction
19.43
-
enzyme recombinantly expressed in Pseudomonas aeruginosa
43.8
-
nondiabetic subjects
47.8
-
type 2 diabetic patients
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.6
-
in presence of 5 mM Mn2+
7.6
-
in presence of 5 mM Mg2+
7.6 - 8.4
-
-
8 - 8.5
8
-
activated by Mg2+, at a MgCl2 concentration double that of ATP
8.3
-
in presence of MgCl2
9
-
in presence of MgATP2-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 12
Leptosphaeria michotii
-
active in this range
7 - 9.3
-
7.0: about 65% of maximal activity, 9.3: about 35% of maximal activity
additional information
-
pH profiles of the ATP-cleavage reaction in the presence and absence of free biotin
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
25 - 35
-
-