Information on EC 2.8.3.5 - 3-oxoacid CoA-transferase and Organism(s) Homo sapiens

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Homo sapiens


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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
2.8.3.5
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RECOMMENDED NAME
GeneOntology No.
3-oxoacid CoA-transferase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
coenzyme A transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ketolysis
-
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TCA cycle VIII (helicobacter)
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citric acid cycle
-
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Synthesis and degradation of ketone bodies
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Valine, leucine and isoleucine degradation
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Butanoate metabolism
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SYSTEMATIC NAME
IUBMB Comments
succinyl-CoA:3-oxo-acid CoA-transferase
Acetoacetate and, more slowly, 3-oxopropanoate, 3-oxopentanoate, 3-oxo-4-methylpentanoate or 3-oxohexanoate can act as acceptors; malonyl-CoA can act instead of succinyl-CoA.
CAS REGISTRY NUMBER
COMMENTARY hide
9027-43-4
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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succinyl-CoA:3-ketoacid CoA transferase deficiency is an inborn error of ketone body metabolism and causes episodic ketoacidosis
metabolism
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SCOT is a key enzyme involved in ketone body metabolism
physiological function
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role of SCOT in insulin secretion
additional information
-
low enzyme expression is correlated with diabetis type 2
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
succinyl-CoA + 3-hydroxybutyrate
succinate + 3-hydroxybutyryl-CoA
show the reaction diagram
-
-
-
-
?
succinyl-CoA + a 3-oxo acid
succinate + a 3-oxoacyl-CoA
show the reaction diagram
succinyl-CoA + acetoacetate
?
show the reaction diagram
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
show the reaction diagram
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
succinyl-CoA + 3-hydroxybutyrate
succinate + 3-hydroxybutyryl-CoA
show the reaction diagram
-
-
-
-
?
succinyl-CoA + a 3-oxo acid
succinate + a 3-oxoacyl-CoA
show the reaction diagram
succinyl-CoA + acetoacetate
?
show the reaction diagram
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
succinyl-CoA
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-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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the DNA region between -2168 and -361 appears to inhibit the SCOT promoter activity in HepG2 cells
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00003
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diabetic pancreatic islets
0.0005
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fibroblast extract, patient with enzyme deficiency
0.0038
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nondiabetic pancreatic islets
additional information
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 40
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100% SCOT activity of wild-type enzyme
30
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59.7% residual SCOT activity of R268H mutant enzyme
37
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34% residual SCOT activity of R268H mutant enzyme
40
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4% residual SCOT activity of R268H mutant enzyme, the R268H mutant protein has temperature-sensitive instability and dramatically reduces residual SCOT activity to 4% wild-type in 40°C expression so that the R268H mutation is a disease-causing mutation in GS10 and GS11 a SCOT-deficient sibling case from South Africa
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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H1e human hepatoma cell line, but no detection in normal hepatocytes, HepG2 hepatoma cells and liver tissues
Manually annotated by BRENDA team
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decreased expression of SCOT protein, neuroblastoma cells are unable to use ketone bodies as an energy source
Manually annotated by BRENDA team
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of healthy individuals and of type 2 diabetes patients: decreased activity by 92% in the diabetic compared with the non-diabetic islets
Manually annotated by BRENDA team
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decreased expression of SCOT protein, neuroblastoma cells are unable to use ketone bodies as an energy source
Manually annotated by BRENDA team
midpiece of ejaculated spermatozoa where mitochondria exist
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
SDS-PAGE
52000
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SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
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x-ray crystallography
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, using 0.20 M sodium chloride, 0.1 M Tris pH 9.0 and 25% (w/v) polyethylene glycol 3350
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42
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incubation of wild type at 42°C for 10 min does not affect enzyme activity, incubation of mutant T435N at 42°C for 10 min reduces enzyme activity to 50%
55
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incubation of wild type at 55°C for 10 min reduces enzyme activity to 20%, incubation of T435N at 55°C results in more rapid inactivation of enzyme activity (below 10% in a 4-min incubation)
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
An analysis of the three-dimensional structure of SCOT shows that the R268H mutation is expected to break a conserved salt bridge between R268 and D52, which would be expected to lead to decreased stability of the protein.
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enzyme is only soluble under denaturating conditions
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography, and Superdex 200 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA from patient with SCOT deficiency
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expressed in Escherichia coli BL21(DE3) cells
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expressed in SCOT-deficient fibroblasts of GS01
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expression in SCOT-deficient SV 40-transformed fibroblasts
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gene SCOT, DNA and amino acid sequence determination and analysis, mutant sequence analysis, overview
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E273X
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
G219E
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
G324E
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
L429F
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
M388V
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
P262R
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R217X
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R268C
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R38C
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
S283X
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
T58M
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missense mutation derived from a SCOT-deficient patient, enzyme is functional
V112D
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V221M
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the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
additional information
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identification of point mutation leading to enzyme inactivation, and deficiency causing severe ketoacidosis in vivo, some mutations lead to highly reduced mRNA and enzyme levels, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine