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Information on EC 2.3.3.8 - ATP citrate synthase and Organism(s) Mus musculus and UniProt Accession Q91V92
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2.3.3.8 ATP citrate synthaseIUBMB Comments
The enzyme can be dissociated into components, two of which are identical with EC 4.1.3.34 (citryl-CoA lyase) and EC 6.2.1.18 (citrate---CoA ligase).
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Word Map
- 2.3.3.8
-
lipogenesis
- carboxylase
-
lipogenic
-
malic
- adipose
- cholesterol
- glucose-6-phosphate
- triglyceride
- histone
- sterol
- lipoprotein
- hydroxycitrate
- malate
- adipocytes
- 6-phosphogluconate
-
acetyl-coenzyme
- carnitine
- isocitrate
-
oleaginous
- statin
-
bempedoic
-
1.1.1.40
- malonyl-coa
-
refeeding
-
cambogia
- ezetimibe
- stearoyl-coa
- srebp-1
-
nadp-isocitrate
- acetoacetyl-coa
-
6.4.1.2
- garcinia
-
refeed
- acetoacetate
- analysis
- drug development
- synthesis
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
atp-citrate lyase, atp citrate lyase, citrate cleavage enzyme, atp:citrate lyase, adenosine triphosphate citrate lyase, atp citrate synthase, atp citrate (pro-s)-lyase, atp-citrate synthase alpha chain protein 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ACL
adenosine triphosphate citrate lyase
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-
-
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ATP citrate (pro-S)-lyase
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-
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ATP-citric lyase
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-
-
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ATP:citrate lyase
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-
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ATP:citrate oxaloacetate lyase ((pro-3S)-CH2COO--> acetyl-CoA) (ATP-dephosphorylating)
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ATP:citrate oxaloacetate-lyase (pro-3S-CH2COO->acetyl-CoA, ATP dephosphorylating)
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-
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ATP:citrate oxaloacetate-lyase CoA-acetylating and ATP-dephosphorylating
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Citrate cleavage enzyme
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-
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citrate-ATP lyase
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-
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citric cleavage enzyme
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-
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ACL
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:oxaloacetate C-acetyltransferase [(pro-S)-carboxymethyl-forming, ADP-phosphorylating]
The enzyme can be dissociated into components, two of which are identical with EC 4.1.3.34 (citryl-CoA lyase) and EC 6.2.1.18 (citrate---CoA ligase).
CAS REGISTRY NUMBER
COMMENTARY
9027-95-6
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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
ADP + phosphate + acetyl-CoA + oxaloacetate
ATP + citrate + CoA
-
-
-
-
?
ATP + citrate + CoA
ADP + phosphate + acetyl-CoA + oxaloacetate
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-
-
?
ATP + citrate + CoA
ADP + phosphate + acetyl-CoA + oxaloacetate
essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. Regulation of the enzyme activity is a potentially important point of control for cell cycle regulation in the myeloid lineage
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-
?
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
ADP + phosphate + acetyl-CoA + oxaloacetate
ATP + citrate + CoA
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-
-
-
?
ATP + citrate + CoA
ADP + phosphate + acetyl-CoA + oxaloacetate
-
-
-
?
ATP + citrate + CoA
ADP + phosphate + acetyl-CoA + oxaloacetate
essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. Regulation of the enzyme activity is a potentially important point of control for cell cycle regulation in the myeloid lineage
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3,5-dichloro-2-hydroxy-N-(4-methoxybiphenyl-3-yl)benzenesulfonamide
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shows an oral availability of 55%, but a half-life of only 2.1 h. After 20 days of treatment, there is a modest lowering of both plasma cholesterol and triglycerides in high-fat fed mice
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
insulin growth factor 1
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induces enzyme activation in an AKT-dependent fashion
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
high glucose promotes ATP-citrate lyase nuclear translocation
high glucose promotes ATP-citrate lyase nuclear translocation
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
ATP citrate lyase plays a key role in regulating mitochondrial function, as well as glucose and lipid metabolism in skeletal muscle. The enzyme increases myoblast and satellite cell differentiation in vitro. It increases MYOD expression by acetyl-H3(K9/14/27) enrichment at the MYOD promoter. It acts downstream of IGF-1 to stimulate myogenesis. IT improves muscle regeneration following cardiotoxin-induced injury
metabolism
physiological function
malfunction
ATP citrate lyase silencing impairs myoblast and satellite cell differentiation, and it is accompanied by a decrease in fast myosin heavy chain isoforms and MYOD
malfunction
upon genetic deletion of Acly, the gene coding for ATP-citrate lyase, cells remain viable and proliferate, although at an impaired rate. In the absence of ACLY, cells upregulate ACSS2 and utilize exogenous acetate to provide acetyl-CoA for de novo lipogenesis and histone acetylation. A physiological level of acetate is sufficient for cell viability and abundant acetyl-CoA production, although histone acetylation levels remain low in ACLY-deficient cells unless supplemented with high levels of acetate. ACLY-deficient adipocytes accumulate lipid in vivo, exhibit increased acetyl-CoA and malonyl-CoA production from acetate, and display some differences in fatty acid content and synthesis. Engagement of acetate metabolism is a crucial, although partial, mechanism of compensation for ACLY deficiency
metabolism
essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis and for histone acetylation. Regulation of the enzyme activity is a potentially important point of control for cell cycle regulation in the myeloid lineage
metabolism
the enzyme plays a critical role in epigenetic regulation of diabetic renal fibrosis. It is essential for high glucose-induced histone hyperacetylation and fibrogenic gene upregulation in mesangial cells
physiological function
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the enzyme is essentially required for embryonic development. Increased enzyme activity is found in the fetal development of the brain
physiological function
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the enzyme regulates mitochondrial function and cardiolipin synthesis and content in skeletal muscle
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). ACLY_MOUSE
1091
0
119728
Swiss-Prot
other Location (Reliability: 2)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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enzyme knockout mutant leads to a significant impairment of glucose-dependent lipid synthesis and an elevation of mitochondrial membrane potential. Cells lacking ATP citrate synthase display decreased cytokine-stimulated cell proliferation. In contrast, these cells resist cell death induced by either cytokine or glucose withdrawal. The mutation significantly impairs Akt-mediated tumorigenesis in vivo
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
mRNA transcript levels decrease during normal macrophage differentiation from bone marrow precursors
sterol regulatory element binding protein-1 up-regulates the enzyme at mRNA level via Akt signaling
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
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3,5-dichloro-2-hydroxy-N-(4-methoxybiphenyl-3-yl)benzenesulfonamide is a cell-permeable inhibitor with modest potency. It shows an oral availability of 55%, but a half-life of only 2.1 h. After 20 days of treatment, there is a modest lowering of both plasma cholesterol and triglycerides in high-fat fed mice
medicine
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ATP citrate synthase inhibition by RNAi or the chemical SB-204990 limits in vitro proliferation and survival of tumor cells displaying aerobic glycolysis. The same treatments also reduce in vivo tumor growth and induce differentiation
medicine
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stable knockdown of ATP citrate synthase significantly impairs Akt-mediated tumorigenesis in vivo
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Li, J.J.; Wang, H.; Tino, J.A.; Robl, J.A.; Herpin, T.F.; Lawrence, R.M.; Biller, S.; Jamil, H.; Ponticiello, R.; Chen, L.; Chu, C.H.; Flynn, N.; Cheng, D.; Zhao, R.; Chen, B.; Schnur, D.; Obermeier, M.T.; Sasseville, V.; Padmanabha, R.; Pike, K.; Harrity, T.
2-Hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors
Bioorg. Med. Chem. Lett.
17
3208-3211
2007
Homo sapiens, Mus musculus
Hatzivassiliou, G.; Zhao, F.; Bauer, D.E.; Andreadis, C.; Shaw, A.N.; Dhanak, D.; Hingorani, S.R.; Tuveson, D.A.; Thompson, C.B.
ATP citrate lyase inhibition can suppress tumor cell growth
Cancer Cell
8
311-321
2005
Homo sapiens, Mus musculus
Bauer, D.E.; Hatzivassiliou, G.; Zhao, F.; Andreadis, C.; Thompson, C.B.
ATP citrate lyase is an important component of cell growth and transformation
Oncogene
24
6314-6322
2005
Mus musculus
Wang, Q.; Jiang, L.; Wang, J.; Li, S.; Yu, Y.; You, J.; Zeng, R.; Gao, X.; Rui, L.; Li, W.; Liu, Y.
Abrogation of hepatic ATP-citrate lyase protects against fatty liver and ameliorates hyperglycemia in leptin receptor-deficient mice
Hepatology
49
1166-1175
2009
Mus musculus
Chypre, M.; Zaidi, N.; Smans, K.
ATP-citrate lyase: a mini-review
Biochem. Biophys. Res. Commun.
422
1-4
2012
Homo sapiens, Mus musculus
Das, S.; Morvan, F.; Jourde, B.; Meier, V.; Kahle, P.; Brebbia, P.; Toussaint, G.; Glass, D.J.; Fornaro, M.
ATP citrate lyase improves mitochondrial function in skeletal muscle
Cell Metab.
21
868-876
2015
Mus musculus
Rodriguez, S.; Denby, C.M.; Van Vu, T.; Baidoo, E.E.; Wang, G.; Keasling, J.D.
ATP citrate lyase mediates cytosolic acetyl-CoA biosynthesis increases mevalonate production in Saccharomyces cerevisiae
Microb. Cell Fact.
15
48
2016
Aspergillus nidulans, Yarrowia lipolytica, Lipomyces starkeyi, Mus musculus, Rhodotorula toruloides
Londono Gentile, T.; Lu, C.; Lodato, P.M.; Tse, S.; Olejniczak, S.H.; Witze, E.S.; Thompson, C.B.; Wellen, K.E.
DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation
Mol. Cell. Biol.
33
3864-3878
2013
Mus musculus
Deb, D.K.; Chen, Y.; Sun, J.; Wang, Y.; Li, Y.C.
ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation and fibrogenic gene upregulation in mesangial cells
Am. J. Physiol. Renal Physiol.
313
F423-F429
2017
Mus musculus (Q91V92)
Rhee, J.; Solomon, L.A.; DeKoter, R.P.
A role for ATP citrate Lyase in cell cycle regulation during myeloid differentiation
Blood Cells Mol. Dis.
76
82-90
2019
Mus musculus (Q91V92)
Zhao, S.; Torres, A.; Henry, R.A.; Trefely, S.; Wallace, M.; Lee, J.V.; Carrer, A.; Sengupta, A.; Campbell, S.L.; Kuo, Y.M.; Frey, A.J.; Meurs, N.; Viola, J.M.; Blair, I.A.; Weljie, A.M.; Metallo, C.M.; Snyder, N.W.; Andrews, A.J.; Wellen, K.E.
ATP-citrate lyase controls a glucose-to-acetate metabolic switch
Cell Rep.
17
1037-1052
2016
Mus musculus (Q91V92)
Das, S.; Morvan, F.; Morozzi, G.; Jourde, B.; Minetti, G.C.; Kahle, P.; Rivet, H.; Brebbia, P.; Toussaint, G.; Glass, D.J.; Fornaro, M.
ATP citrate lyase regulates myofiber differentiation and increases regeneration by altering histone acetylation
Cell Rep.
21
3003-3011
2017
Homo sapiens (P53396), Mus musculus (Q91V92), Mus musculus
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