Information on EC 6.2.1.7 - cholate-CoA ligase

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

EC NUMBER
COMMENTARY hide
6.2.1.7
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RECOMMENDED NAME
GeneOntology No.
cholate-CoA ligase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + cholate + CoA = AMP + diphosphate + choloyl-CoA
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid-thiol ligation
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
bile acid biosynthesis, neutral pathway
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bile acids degradation
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Metabolic pathways
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Primary bile acid biosynthesis
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Secondary bile acid biosynthesis
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bile acid biosynthesis, neutral pathway
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SYSTEMATIC NAME
IUBMB Comments
cholate:CoA ligase (AMP-forming)
Requires Mg2+ for activity. The mammalian enzyme is membrane-bound and catalyses the first step in the conjugation of bile acids with amino acids, converting bile acids into their acyl-CoA thioesters. Chenodeoxycholate, deoxycholate, lithocholate and trihydroxycoprostanoate can also act as substrates [7]. The bacterial enzyme is soluble and participates in an anaerobic bile acid 7 alpha-dehydroxylation pathway [5].
CAS REGISTRY NUMBER
COMMENTARY hide
9027-90-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain VPI 12708
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-
Manually annotated by BRENDA team
strain VPI 12708
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
no activity in Homo sapiens
no activity detected in HepG2 hepatoblastoma cells
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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defects in cholate-CoA ligase and bile acid-CoA:amino acid N-acyltransferase activities can cause intrahepatic cholestasis, overview
physiological function
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cholate-CoA ligase and bile acid-CoA:amino acid N-acyltransferase sequentially mediate bile-acid amidation
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanate + CoA
AMP + diphosphate + 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA
show the reaction diagram
ATP + chenodeoxycholate + CoA
AMP + diphosphate + chenodeoxycholoyl-CoA
show the reaction diagram
ATP + cholate + CoA
?
show the reaction diagram
ATP + cholate + CoA
AMP + diphosphate + choloyl-CoA
show the reaction diagram
ATP + deoxycholate + CoA
AMP + diphosphate + deoxycholoyl-CoA
show the reaction diagram
ATP + lithocholate + CoA
AMP + diphosphate + lithocholoyl-CoA
show the reaction diagram
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-
-
-
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dATP + cholate + CoA
dAMP + diphosphate + choloyl-CoA
show the reaction diagram
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-
-
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additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanate + CoA
AMP + diphosphate + 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA
show the reaction diagram
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-
-
?
ATP + cholate + CoA
?
show the reaction diagram
ATP + cholate + CoA
AMP + diphosphate + choloyl-CoA
show the reaction diagram
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re-activation and re-conjugation of bile acids
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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modest enhancement of activity
Fe2+
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modest enhancement of activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid
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0.005 mM, 63% inhibition of the activity with chenodeoxycholate
AMP
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competitive versus ATP
ATP
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inhibition above 3 mM
Bile acids
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conjugated bile acids are less efficient inhibitors than unconjugated bile acids, deoxycholate is the most potent
cholic acid
choloyl-CoA
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uncompetitive versus CoA
deoxycholate
deoxycholic acid
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0.02 mM, 60% inhibition
diacetyl
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inactivation by modification of arginine residues, ATP protects
diphosphate
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fatty acids
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inhibition is not important in vivo owing to the high concentrations required for inhibition
lithocholic acid
NEM
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biphasic effect: at short reaction times ligase activity increases, but further reaction leads to nearly complete inactivation
norcholic acid
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0.02 mM, 18% inhibition
oleic acid
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palmitate
palmitoleic acid
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Phenylglyoxal
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inactivation by modification of arginine residues, ATP protects
taurocholate
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trihydroxycoprostanoic acid
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; 0.02 mM, 24% inhibition
Triton X-100
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
bovine serum albumin
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activation
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dithiothreitol
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activation
NEM
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biphasic effect: at short reaction times ligase activity increases, but further reaction leads to nearly complete inactivation
Phospholipid
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addition of phospholipids is necessary to restore the activity of the delipidated enzyme stabilized by high concentrations of glucose and sucrose
Triton X-100
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activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2 - 0.65
ATP
0.018 - 0.08
chenodeoxycholate
0.006 - 0.05
cholate
0.038
CoA
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0.053
deoxycholate
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0.04
lithocholate
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0015
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0.0018
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activity of microsomal extraxt
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 7.3
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8
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6.0: about 40% of maximal activity, 8.0: about 50% of maximal activity
6.5 - 9.8
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6.5: about 30% of maximal activity, 9.8: about 50% of maximal activity
8 - 9.6
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pH 8.0: about 75% of maximal activity, pH 9.6: about 75% of maximal activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58294
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2 * 58294, calculation from nucleotide sequence
65000
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x * 65000, SDS-PAGE
212000
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gel filtration
243000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
41
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half-life is about 16 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PMSF, 0.1 M, can counteract the inactivation of the enzyme at 4°C
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the lability of the delipidated enzyme can be suppressed by high concentrations of polyols such as sucrose and glucose
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
unstable at 4°C. PMSF, 0.1 M, can counteract the inactivation of the enzyme
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when glucose and Triton H-666 are added together to lipid-poor Triton X-100 solubilized preparations, enzyme activity remains stable for at least 3 months at -20°C or for 2 days at 4°C
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning and sequencing of a bile acid-inducible operon. The polypeptides encoded by this operon are involved in the multistep 7-dehydroxylation pathway
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expressed in COS-1 cells
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expression in Escherichia coli
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expression of rBAL in Sf9 insect cells
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis