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Information on EC 2.3.3.1 - citrate (Si)-synthase and Organism(s) Homo sapiens

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EC Tree
     2 Transferases
         2.3 Acyltransferases
             2.3.3 Acyl groups converted into alkyl groups on transfer
                2.3.3.1 citrate (Si)-synthase
IUBMB Comments
The stereospecificity of this enzyme is opposite to that of EC 2.3.3.3, citrate (Re)-synthase, which is found in some anaerobes. Citrate synthase for which the stereospecificity with respect to C-2 of oxaloacetate has not been established are included in EC 2.3.3.16, citrate synthase (unknown stereospecificity).
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
citrate synthase, citrate (si)-synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(R)-citric synthase
-
-
-
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citrate oxaloacetate-lyase ((pro-3S)-CH2COO---> acetyl-CoA)
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-
-
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citrate synthase
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citrate synthase isoform a
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citrate synthase isoform b
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-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
addition
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-
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:oxaloacetate C-acetyltransferase [thioester-hydrolysing, (pro-S)-carboxymethyl forming]
The stereospecificity of this enzyme is opposite to that of EC 2.3.3.3, citrate (Re)-synthase, which is found in some anaerobes. Citrate synthase for which the stereospecificity with respect to C-2 of oxaloacetate has not been established are included in EC 2.3.3.16, citrate synthase (unknown stereospecificity).
CAS REGISTRY NUMBER
COMMENTARY hide
9027-96-7
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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 + H2O + oxaloacetate
citrate + CoA
show the reaction diagram
acetyl-CoA + oxaloacetate + H2O
citrate + CoA
show the reaction diagram
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-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3,3-thiodipropionate
substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive
3,3-thiodipropionic acid
competitive inhibition versus acetyl-CoA and versus oxaloacetate
3-phosphonopropionic acid
competitive inhibition versus acetyl-CoA and versus oxaloacetate
3-phosphopropionate
substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive
Dihydroxyfumarate
substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive
dihydroxyfumaric acid
competitive inhibition versus acetyl-CoA and versus oxaloacetate
DL-malate
substrate acetyl-CoA, mixed type inhibition; substrate oxaloacetate, mixed type inhibition
DL-malic acid
mixed type inhibition versus acetyl-CoA and versus oxaloacetate
Maleate
substrate acetyl-CoA, mixed type inhibition; substrate oxaloacetate, mixed type inhibition
Maleic acid
mixed type inhibition versus acetyl-CoA and versus oxaloacetate
potassium hydroxycitrate
competitive inhibition versus acetyl-CoA and versus oxaloacetate; substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive
propionate
competitive inhibition versus oxaloacetate, mixed type inhibition versus acetyl-CoA; substrate acetyl-CoA, competitive; substrate oxaloacetate, competitive
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0077 - 0.0104
acetyl-CoA
0.0036 - 0.0057
oxaloacetate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
117 - 260
acetyl-CoA
111 - 208
oxaloacetate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
11000 - 34000
acetyl-CoA
19000 - 59000
oxaloacetate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
22.3 - 24.2
3,3-thiodipropionate
22.3 - 24.2
3,3-thiodipropionic acid
21.2 - 71.7
3-phosphonopropionic acid
21.2 - 71.7
3-phosphopropionate
73 - 90.5
Dihydroxyfumarate
73 - 90.5
dihydroxyfumaric acid
6.5 - 14.2
DL-malate
6.5 - 14.2
DL-malic acid
17.5 - 20
Maleate
17.5 - 20
Maleic acid
8 - 14.6
potassium hydroxycitrate
25.1 - 28.1
propionate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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activity in trained and untrained skeletal muscle, highest in acutely trained muscle due to mitochondrial membrane breakdown, mechanism
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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enzyme assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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enzyme assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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cancer and normal tissue
Manually annotated by BRENDA team
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activity of citrate synthase is significantly higher compared with adjacent nonneoplastic tissue
Manually annotated by BRENDA team
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trained and untrained
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
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citrate synthase is a key enzyme of the citric acid cycle that provides energy for cellular function. Additionally, the enzyme plays a critical role in providing citrate derived acetyl-CoA for lipogenesis and cholesterologenesis
physiological function
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the citrate synthase gene is a direct retinoic acid receptor-related orphan receptor alpha target and one mechanism by which retinoic acid receptor-related orphan receptor alpha regulates lipid metabolism is via regulation of citrate synthase expression
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CISY_HUMAN
466
0
51712
Swiss-Prot
Mitochondrion (Reliability: 3)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
comparison of crystal structures of human enzyme and Aspergillus fumigatus 2-methylcitrate synthase, EC 2.3.3.5, both wild-type and mutants A348G and G352A, respectively
crystallization is performed at room temperature using the sitting-drop vapor diffusion method and MRC 2-drop 96-well crystallization plates
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A348G
mutation to the corresponding residue of Aspergillus fumigatus 2-methylcitrate synthase. Active site residues Arg448 (chain B) and His347 (chain A) are not in their normal positions for oxaloacetate binding
G386A
insoluble enzyme variant
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EGFP-fusion version expressed in HeLa cell
expressed in Hep-G2 cells
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expression in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
overexpression of retinoic acid receptor-related orphan receptor alpha (5fold), leads to a 94% increase in citrate synthase mRNA levels and enzyme activity in Hep-G2 cells
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Leek, B.T.; Mudaliar, S.R.; Henry, R.; Mathieu-Costello, O.; Richardson, R.S.
Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle
Am. J. Physiol.
280
R441-447
2001
Homo sapiens
Manually annotated by BRENDA team
Schlichtholz, B.; Turyn, J.; Goyke, E.; Biernacki, M.; Jaskiewicz, K.; Sledzinski, Z.; Swierczynski, J.
Enhanced citrate synthase activity in human pancreatic cancer
Pancreas
30
99-104
2005
Homo sapiens
Manually annotated by BRENDA team
Cheng, T.L.; Liao, C.C.; Tsai, W.H.; Lin, C.C.; Yeh, C.W.; Teng, C.F.; Chang, W.T.
Identification and characterization of the mitochondrial targeting sequence and mechanism in human citrate synthase
J. Cell. Biochem.
107
1002-1015
2009
Homo sapiens, Homo sapiens (O75390)
Manually annotated by BRENDA team
Crumbley, C.; Wang, Y.; Banerjee, S.; Burris, T.P.
Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor alpha (RORalpha)
PLoS ONE
7
e33804
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Schlachter, C.R.; Klapper, V.; Radford, T.; Chruszcz, M.
Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase
Biol. Chem.
400
1567-1581
2019
Homo sapiens (O75390), Homo sapiens
Manually annotated by BRENDA team