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Information on EC 2.8.3.5 - 3-oxoacid CoA-transferase and Organism(s) Homo sapiens
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2.8.3.5 3-oxoacid CoA-transferaseIUBMB Comments
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.
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Word Map
- 2.8.3.5
- ketone
- acetoacetyl-coa
-
thiolase
- 3-hydroxybutyrate
-
ketolytic
-
ketogenic
- ketosis
- butyryl-coa
-
ketoacidotic
- acetobutylicum
-
butyrate-producing
-
butyryl-coa:acetate
-
ketone-body
- tyrobutyricum
- medicine
-
hydrogenosomes
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
coa transferase, oxct1, 3-oxoacid coa-transferase, succinyl-coa:3-ketoacid coa transferase, 3-ketoacid coa-transferase, succinyl-coa transferase, scot-t, succinyl-coa:3-oxoacid coa transferase, succinyl-coa:3-oxoacid coa-transferase, succinyl-coa:3-ketoacid coenzyme a transferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3-ketoacid CoA-transferase
-
-
-
-
3-ketoacid coenzyme A transferase
-
-
-
-
3-ketoacid coenzyme A-transferase
-
-
-
-
3-oxo-CoA transferase
-
-
-
-
3-oxoacid CoA dehydrogenase
-
-
-
-
3-oxoacid coenzyme A-transferase
-
-
-
-
acetoacetate succinyl-CoA transferase
-
-
-
-
acetoacetyl coenzyme A-succinic thiophorase
-
-
-
-
coenzyme A-transferase, 3-oxoacid
-
-
-
-
OXCT1
SCOT
SCOT-t
-
-
-
-
succinyl coenzyme A-acetoacetyl coenzyme A-transferase
-
-
-
-
succinyl-CoA transferase
-
-
-
-
succinyl-CoA:3-ketoacid CoA transferase
succinyl-CoA:acetoacetate CoA transferase
-
-
-
-
testis-specific succinyl-CoA:3-oxo-acid CoA-transferase
-
-
-
-
SCOT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
coenzyme A transfer
coenzyme A transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -
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
9027-43-4
-
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
succinyl-CoA + a 3-oxo acid
succinate + a 3-oxoacyl-CoA
-
ketone bodies, produced mainly in the liver, are an important source of energy for extrahepatic tissues
-
-
?
succinyl-CoA + acetoacetate
?
-
rate determining step of ketolysis in extrahepatic tissues
-
-
?
succinyl-CoA + acetoacetate
?
-
enzyme deficiency leads to ketoacidotic crises and persistent ketosis
-
-
?
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
-
-
-
-
?
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
-
key enzyme for ketone body utilization, SCOT deficiency causes episodes of severe ketoacidosis
-
-
r
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
the activation of acetoacetate to acetoacetyl-CoA by SCOT is essential for use of ketone bodies as an energy source
-
-
?
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
succinyl-CoA + a 3-oxo acid
succinate + a 3-oxoacyl-CoA
-
ketone bodies, produced mainly in the liver, are an important source of energy for extrahepatic tissues
-
-
?
succinyl-CoA + acetoacetate
?
-
rate determining step of ketolysis in extrahepatic tissues
-
-
?
succinyl-CoA + acetoacetate
?
-
enzyme deficiency leads to ketoacidotic crises and persistent ketosis
-
-
?
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
-
key enzyme for ketone body utilization, SCOT deficiency causes episodes of severe ketoacidosis
-
-
r
succinyl-CoA + acetoacetate
succinate + acetoacetyl-CoA
the activation of acetoacetate to acetoacetyl-CoA by SCOT is essential for use of ketone bodies as an energy source
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the DNA region between -2168 and -361 appears to inhibit the SCOT promoter activity in HepG2 cells
-
additional information
-
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
LITERATURE
additional information
additional information
-
mutant T435N shows 20% of wild type activity at 39.5°C, 25% at 37°C, and 50% at 30°C
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
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
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
H1e human hepatoma cell line, but no detection in normal hepatocytes, HepG2 hepatoma cells and liver tissues
-
decreased expression of SCOT protein, neuroblastoma cells are unable to use ketone bodies as an energy source
-
of healthy individuals and of type 2 diabetes patients: decreased activity by 92% in the diabetic compared with the non-diabetic islets
-
decreased expression of SCOT protein, neuroblastoma cells are unable to use ketone bodies as an energy source
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
-
low enzyme expression is correlated with diabetis type 2
malfunction
-
succinyl-CoA:3-ketoacid CoA transferase deficiency is an inborn error of ketone body metabolism and causes episodic ketoacidosis
malfunction
overexpression of OXCT1 enhances sensitivity to cisplatin in the SK-OV-3 OC cell line
physiological function
3-oxoacid-CoA transferase 1 (OXCT1) is a homodimeric mitochondrial matrix enzyme that serves a central role in extrahepatic ketone body catabolism (ketone bodies to acetyl-CoA to mitochondrial tricarboxylic acid cycle entrance). OXCT1 overexpression in a cisplatin-resistant cell line improves sensitivity to cisplatin. Natural sensitivity to cisplatin is observed in the eight human ovarian cell lines SK-OV-3, PA-1, Caov-3, TOV-21 G, TOV-112D, OV-90, OVCAR-3 and A2780
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SCOT1_HUMAN
520
0
56158
Swiss-Prot
Mitochondrion (Reliability: 2)
SCOT2_HUMAN
517
0
56140
Swiss-Prot
Mitochondrion (Reliability: 1)
B3KS89_HUMAN
517
0
56126
TrEMBL
Mitochondrion (Reliability: 1)
Q6IAV5_HUMAN
520
0
56192
TrEMBL
Mitochondrion (Reliability: 2)
A0A024R040_HUMAN
520
0
56158
TrEMBL
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A215V
C456F
E273X
G219E
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
G324E
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
L327P
L429F
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
M388V
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
P262R
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R217X
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R268C
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R268H
R38C
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R468C
S226N
S283X
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
S405P
T435N
T58M
-
missense mutation derived from a SCOT-deficient patient, enzyme is functional
V112D
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V133E
V221M
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V404F
additional information
A215V
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
A215V
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency and retains 3.5% residual activity
C456F
-
missense mutation derived from a SCOT-deficient patient, no enzyme activity
C456F
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
E273X
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
E273X
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
L327P
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
L327P
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency and retains 4.7% residual activity
R268H
-
DNA mutation in a south african human with SCOT deficiency, detected in fibroblasts
R268H
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R468C
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
R468C
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency and retains 12% and 51% of wild type residual activities at 37 and 30°C, respectively
S226N
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
S226N
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency showing no residual activity
S405P
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
S405P
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency and retains no residual activity
T435N
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V133E
-
missense mutation derived from a SCOT-deficient patient, no enzyme activity
V133E
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V404F
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency
V404F
-
the mutation is associated with succinyl-CoA:3-ketoacid CoA transferase deficiency and retains some residual activity
additional information
-
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
additional information
sensitization of cells to cisplatin following overexpression of OXCT1 , overexpression of OXCT1 enhances sensitivity to cisplatin, one of the most effective broad-spectrum anticancer drugs, in the SK-OV-3 OC ovarian cancer cell line. Overexpression of OXCT1 significantly decreases the IC50 for cisplatin by about 21% compared with EGFP-transfected control cells
additional information
-
sensitization of cells to cisplatin following overexpression of OXCT1 , overexpression of OXCT1 enhances sensitivity to cisplatin, one of the most effective broad-spectrum anticancer drugs, in the SK-OV-3 OC ovarian cancer cell line. Overexpression of OXCT1 significantly decreases the IC50 for cisplatin by about 21% compared with EGFP-transfected control cells
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42
-
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
-
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.
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene OXCT1 , transient overexpression of OXCT1 in SK-OV-3 OC cells, the level of OXCT1 expresxadsion is increased to 161.5fold in OXCT1-transfected cells
gene SCOT, DNA and amino acid sequence determination and analysis, mutant sequence analysis, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
OXCT1 expression is suppressed by DNA methylation in the cisplatin-resistant group
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
patients homozygous for T435N mutation of SCOT do not show permanent ketosis
medicine
-
Succinyl-CoA:3-ketoacid CoA transferase deficiency causes episodic ketoacidosis
medicine
-
dietary manipulation using ketone bodies in accordance with SCOT expression may be a novel therapeutic strategy for neuroblastoma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Berry, G.T.; Fukao, T.; Mitchell, G.A.; Mazur, A.; Ciafre, M.; Gibson, J.; Kondo, N.; Palmieri, M.J.
Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency
J. Inherit. Metab. Dis.
24
587-595
2001
Homo sapiens
Kassovska-Bratinova, S.; Fukao, T.; Song, X.Q.; Duncan, A.M.V.; Chen, H.S.; Robert, M.F.; Perez-Cerda, C.; Ugarte, M.; Chartrand, C.; et al.
Succinyl CoA:3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient
Am. J. Hum. Genet.
59
519-528
1996
Homo sapiens
Song, X.Q.; Fukao, T.; Mitchell, G.A.; Kassovska-Bratinova, S.; Ugarte, M.; Wanders, R.J.; Hirayama, K.; Shintaku, H.; Churchill, P.; Watanabe, H.; Orii, T.; Kondo, N.
Succinyl-CoA:3-ketoacid coenzyme A transferase (SCOT): development of an antibody to human SCOT and diagnostic use in hereditary SCOT deficiency
Biochim. Biophys. Acta
1360
151-156
1997
Homo sapiens
Song, X.Q.; Fukao, T.; Watanabe, H.; Shintaku, H.; Hirayama, K.; Kassovska-Bratinova, S.; Kondo, N.; Mitchell, G.A.
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: two pathogenic mutations, V133E and C456F, in Japanese siblings
Hum. Mutat.
12
83-88
1998
Homo sapiens
Tanaka, H.; Kohroki, J.; Iguchi, N.; Onishi, M.; Nishimune, Y.
Cloning and characterization of a human orthologue of testis-specific succinyl CoA: 3-oxo acid CoA transferase (Scot-t) cDNA
Mol. Hum. Reprod.
8
16-23
2002
Homo sapiens (Q9BYC2), Homo sapiens
Fukao, T.; Shintaku, H.; Kusubae, R.; Zhang, G.X.; Nakamura, K.; Kondo, M.; Kondo, N.
Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA Transferase (SCOT) do not show permanent ketosis
Pediatr. Res.
56
858-863
2004
Homo sapiens
Yamada, K.; Fukao, T.; Zhang, G.; Sakurai, S.; Ruiter, J.P.; Wanders, R.J.; Kondo, N.
Single-base substitution at the last nucleotide of exon 6 (c.671G>A), resulting in the skipping of exon 6, and exons 6 and 7 in human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene
Mol. Genet. Metab.
90
291-297
2007
Homo sapiens
Fukao, T.; Kursula, P.; Owen, E.P.; Kondo, N.
Identification and characterization of a temperature-sensitive R268H mutation in the human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene
Mol. Genet. Metab.
92
216-221
2007
Homo sapiens
Orii, K.E.; Fukao, T.; Song, X.Q.; Mitchell, G.A.; Kondo, N.
Liver-specific silencing of the human gene encoding succinyl-CoA: 3-ketoacid CoA transferase
Tohoku J. Exp. Med.
215
227-236
2008
Homo sapiens (P55809), Homo sapiens
MacDonald, M.J.; Longacre, M.J.; Langberg, E.C.; Tibell, A.; Kendrick, M.A.; Fukao, T.; Ostenson, C.G.
Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes
Diabetologia
52
1087-1091
2009
Homo sapiens
Skinner, R.; Trujillo, A.; Ma, X.; Beierle, E.
Ketone bodies inhibit the viability of human neuroblastoma cells
J. Pediatr. Surg.
44
212-216
2009
Homo sapiens
Fukao, T.; Sass, J.O.; Kursula, P.; Thimm, E.; Wendel, U.; Ficicioglu, C.; Monastiri, K.; Guffon, N.; Bari?, I.; Zabot, M.T.; Kondo, N.
Clinical and molecular characterization of five patients with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency
Biochim. Biophys. Acta
1812
619-624
2011
Homo sapiens
Shafqat, N.; Kavanagh, K.L.; Sass, J.O.; Christensen, E.; Fukao, T.; Lee, W.H.; Oppermann, U.; Yue, W.W.
A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency
J. Inherit. Metab. Dis.
36
983-987
2013
Homo sapiens (P55809), Homo sapiens
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