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Information on EC 2.3.1.9 - acetyl-CoA C-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9BWD1

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EC Tree
IUBMB Comments
The enzyme, found in both eukaryotes and prokaryotes, catalyses the Claisen condensation of an acetyl-CoA and an acyl-CoA (often another acetyl-CoA), leading to the formation of an acyl-CoA that is longer by two carbon atoms. The reaction starts with the acylation of a nucleophilic cysteine at the active site, usually by acetyl-CoA but potentially by a different acyl-CoA, with concomitant release of CoA. In the second step the acyl group is transferred to an acetyl-CoA molecule. cf. EC 2.3.1.16, acetyl-CoA C-acyltransferase.
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Homo sapiens
UNIPROT: Q9BWD1
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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2
acetyl-CoA
=
CoA
+
acetoacetyl-CoA
2
=
+
Synonyms
acetoacetyl-coa thiolase, acetyl-coa acetyltransferase, erg10, acoat, acetyl-coa c-acetyltransferase, cytosolic acetoacetyl-coa thiolase, 2-methylacetoacetyl-coa thiolase, osat1, acetoacetyl coa thiolase, aact2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2-methylacetoacetyl-CoA thiolase
-
-
-
-
3-oxothiolase
-
-
-
-
acetoacetyl CoA thiolase
acetoacetyl-CoA thiolase
acetoacetyl-CoA thiolase T2
-
-
acetyl coenzyme A thiolase
-
-
-
-
acetyl-CoA acetyltransferase
-
-
-
-
acetyl-CoA:N-acetyltransferase
-
-
-
-
acetyltransferase, acetyl coenzyme A
-
-
-
-
beta-acetoacetyl coenzyme A thiolase
-
-
-
-
thiolase II
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 acetyl-CoA = CoA + acetoacetyl-CoA
show the reaction diagram
Claisen condensation, mechanism
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Claisen condensation
-
condensation
-
-
-
-
Acyl group transfer
-
-
-
-
thiolytic cleavage
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:acetyl-CoA C-acetyltransferase
The enzyme, found in both eukaryotes and prokaryotes, catalyses the Claisen condensation of an acetyl-CoA and an acyl-CoA (often another acetyl-CoA), leading to the formation of an acyl-CoA that is longer by two carbon atoms. The reaction starts with the acylation of a nucleophilic cysteine at the active site, usually by acetyl-CoA but potentially by a different acyl-CoA, with concomitant release of CoA. In the second step the acyl group is transferred to an acetyl-CoA molecule. cf. EC 2.3.1.16, acetyl-CoA C-acyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
9027-46-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetyl-CoA
CoA + acetoacetyl-CoA
show the reaction diagram
2-methylacetoacetyl-CoA + CoA
acetyl-CoA + propionyl-CoA
show the reaction diagram
acetoacetyl-CoA + CoA
2 acetyl-CoA
show the reaction diagram
acetyl-CoA + acetyl-CoA
CoA + acetoacetyl-CoA
show the reaction diagram
CoA + acetoacetyl-CoA
acetyl-CoA + acetyl-CoA
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetyl-CoA
CoA + acetoacetyl-CoA
show the reaction diagram
involved in fatty acid synthesis
-
-
r
2-methylacetoacetyl-CoA + CoA
acetyl-CoA + propionyl-CoA
show the reaction diagram
-
cleavage of 2-methylacetoacetyl-CoA in the isoleucine catabolism
-
-
?
acetoacetyl-CoA + CoA
2 acetyl-CoA
show the reaction diagram
-
interconversion of 2 acetyl-CoA into acetoacetyl-CoA in the ketone body metabolism
-
-
r
acetyl-CoA + acetyl-CoA
CoA + acetoacetyl-CoA
show the reaction diagram
-
enzyme deficiency affects isoleucine and ketone body metabolism
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cl-
-
the crystal structures of T2 show that each T2 subunit has a binding site for a chloride ion and a potassium ion. Each of these ion binding sites is defined well by loops at the active site, resulting in the stabilization of the catalytic loops
K+
-
the crystal structures of T2 show that each T2 subunit has a binding site for a chloride ion and a potassium ion. Each of these ion binding sites is defined well by loops at the active site, resulting in the stabilization of the catalytic loops
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetoacetyl-CoA
-
substrate inhibition beyond 0.0225 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005 - 0.01
acetoacetyl-CoA
0.028 - 0.05
CoA
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Uniprot
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
mitochondrial acetoacetyl CoA thiolase is decreased by 80% in ulcerative colitis compared with control. Mitochondrial thiolase activity in ulcerative colitis does not correlate with clinical, endoscopic or histological indices of disease severity. Mitochondrial thiolase activity is reduced in the normal right colon mucosa of patients with left-sided ulcerative colitis
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme deficiency is a rare metabolic disease of autosomal recessive inheritance characterized by intermittent ketoacidotic episodes with onset in the infant period and decline with age, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
THIC_HUMAN
397
0
41351
Swiss-Prot
other Location (Reliability: 4)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
four identical subunits
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
only successful in the presence of CoA
hanging drop vapor diffusion method at 4°C. Unliganded and liganded (with CoA and with K+) structures of the human mitochondrial recombinant tetrameric thiolase
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E252del
M193T
-
naturally occuring mutation leading to enzyme deficiency and to the ketoacidotic episode phenotype, but with differing clinical severity, overview
N158D
N158S
N282H
N353K
Q272X
-
no residual activity under any condition
R208Q
Y219H
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
wild-type T2 protein is stable even after chasing for 48 h at 37°C. The amount of E252del mutant protein at 48 h incubation with cycloheximide is estimated to be 50% of that observed at 0 h. E252del mutant T2 is unstable compared to the wild-type protein at 37°C
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Fukao, T.; Matsuo, N.; Zhang, G.X.; Urasawa, R.; Kubo, T.; Kohno, Y.; Kondo, N.
Single base substitutions at the initiator codon in the mitochondrial acetoacetyl-CoA thiolase (ACAT1/T2) gene result in production of varying amounts of wild-type T2 polypeptide
Hum. Mutat.
21
587-592
2003
Homo sapiens
Manually annotated by BRENDA team
Kursula, P.; Sikkilae, H.; Fukao, T.; Kondo, N.; Wierenga, R.K.
High resolution crystal structures of human cytosolic thiolase (CT): A comparison of the active sites of human CT, bacterial thiolase, and bacterial KAS I
J. Mol. Biol.
347
189-201
2005
Escherichia coli, Homo sapiens (Q9BWD1), Homo sapiens, Zoogloea ramigera (P07097), Zoogloea ramigera
Manually annotated by BRENDA team
Sakurai, S.; Fukao, T.; Haapalainen, A.M.; Zhang, G.; Yamada, K.; Lilliu, F.; Yano, S.; Robinson, P.; Gibson, M.K.; Wanders, R.J.; Mitchell, G.A.; Wierenga, R.K.; Kondo, N.
Kinetic and expression analyses of seven novel mutations in mitochondrial acetoacetyl-CoA thiolase (T2): Identification of a K(m) mutant and an analysis of the mutational sites in the structure
Mol. Genet. Metab.
90
370-378
2007
Homo sapiens
Manually annotated by BRENDA team
Haapalainen, A.M.; Merilaeinen, G.; Pirilae, P.L.; Kondo, N.; Fukao, T.; Wierenga, R.K.
Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function
Biochemistry
46
4305-4321
2007
Homo sapiens
Manually annotated by BRENDA team
Santhanam, S.; Venkatraman, A.; Ramakrishna, B.S.
Impairment of mitochondrial acetoacetyl CoA thiolase activity in the colonic mucosa of patients with ulcerative colitis
Gut
56
1543-1549
2007
Homo sapiens
Manually annotated by BRENDA team
Fukao, T.; Boneh, A.; Aoki, Y.; Kondo, N.
A novel single-base substitution (c.1124A>G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene
Mol. Genet. Metab.
94
417-421
2008
Homo sapiens
Manually annotated by BRENDA team
Thuemmler, S.; Dupont, D.; Acquaviva, C.; Fukao, T.; de Ricaud, D.
Different clinical presentation in siblings with mitochondrial acetoacetyl-CoA thiolase deficiency and identification of two novel mutations
Tohoku J. Exp. Med.
220
27-31
2010
Homo sapiens
Manually annotated by BRENDA team