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ATP + acetate + CoA
AMP + diphosphate + acetyl-CoA
-
45% of the activity relative to acetoacetate
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
ATP + L-3-hydroxybutanoate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
ATP + L-3-hydroxybutyrate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
-
-
-
?
additional information
?
-
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
no activity with GTP, UTP, CTP or ADP
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
no activity with GTP and CTP
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
r
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
no activity with GTP, UTP, CTP or ADP
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
r
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
no activity with GTP, UTP, CTP or ADP
-
?
ATP + acetoacetate + CoA
AMP + diphosphate + acetoacetyl-CoA
-
-
-
-
?
ATP + L-3-hydroxybutanoate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
-
20% of the activity relative to acetoacetate
-
-
?
ATP + L-3-hydroxybutanoate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
-
48% of the activity relative to acetoacetate
-
-
?
ATP + L-3-hydroxybutanoate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
-
about 15% of the activity relative to ATP
-
-
?
ATP + L-3-hydroxybutanoate + CoA
AMP + diphosphate + L-3-hydroxybutyryl-CoA
-
about 15% of the activity relative to ATP
-
-
?
additional information
?
-
-
AACS promoter activity is controlled mainly by C/EBP? during adipogenesis
-
-
?
additional information
?
-
-
primary role of acetoacetate as a substrate in lipogenesis is to promote cholesterol biosynthesis. Regulation of acetoacetyl-CoA synthetase is synchronized with the regulation of cholesterol biosynthesis
-
-
?
additional information
?
-
-
enzyme normally functions in the re-utilization of some of the acetoacetate produced within the mitochondrion as well as that reaching the cytoplasm
-
-
?
additional information
?
-
-
AACS in adipose tissue plays an important role in utilizing ketone bodies for the fatty acid-synthesis during adipose tissue development
-
-
?
additional information
?
-
-
SlAacS is a bona fide acetoacetyl-CoA synthetase, an AMP-forming acyl-CoA synthetase
-
-
?
additional information
?
-
-
SlAacS is a bona fide acetoacetyl-CoA synthetase, an AMP-forming acyl-CoA synthetase
-
-
?
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malfunction
-
knockdown of AACS inhibits differentiation of 3T3-L1 cells and suppresses expression of the adipocyte markers, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha
malfunction
knockdown of SREBP-2, which orchestrates cholesterol synthesis, results in the downregulation of AACS mRNA levels. Knockdown of AACS results in a decrease in histone deacetylase 9, associated with gene silencing
malfunction
overexpression of recombinant mutants N500Q, N503Q, or N547Q, as well as of the wild-type enzyme, increases the ketone body-utilizing activity of HEK-293 cells, but that of N545Q does not. Overexpression of wild-type AACS, N500Q, or N503Q has no effect on legumain activity, but mutations N545Q and N547Q significantly reduce the activity compared to wild-type
metabolism
-
AACS is involved in the pathway of ketone body metabolism, overview
metabolism
Legumain is involved in the cleavage of AACS in the kidney, suggesting that AACS is degraded by the lysosomal pathway
metabolism
acetoacetyl-CoA synthetase (AACS) is responsible for the synthesis of cholesterol and fatty acids. It is cleaved by legumain, a lysosomal asparaginyl endopeptidase. Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA. Overexpression of the cleaved form of AACS (1-547) increases the protein expression of caveolin-1, the principal component of the caveolae. Cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes
metabolism
-
AACS is involved in the pathway of ketone body metabolism, overview
-
metabolism
-
Legumain is involved in the cleavage of AACS in the kidney, suggesting that AACS is degraded by the lysosomal pathway
-
physiological function
-
AACS plays an important role in cholesterol homeostasis
physiological function
-
acetoacetyl-CoA synthetase activates ketone bodies and incorporates them into cholesterol and fatty acids in the cytosol of lipogenic tissue
physiological function
-
acetoacetyl-CoA synthetase activity is required for growth of Streptomyces lividans on acetoacetate and is controlled by a protein acetyltransferase with unique domain organization
physiological function
-
the enzyme has a crucial role in the mechanism of 3T3-L1 differentiation
physiological function
acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme and is responsible for the synthesis of cholesterol and fatty acids. Overexpression of wild-type AACS and AACS (1-547) increased the protein expression of caveolin-1, a scaffolding protein and the principal component of the caveolae, in the cytosol of liver cells. Enzyme AACS has a unique role in caveolae/lipid rafts
physiological function
acetoacetyl-CoA synthetase (AACS) is the enzyme responsible for cholesterol and fatty acid synthesis in the cytosol. AACS has an important role in normal neuronal development. Specificity protein 1 (Sp1) regulates gene expression of AACS in Neuro-2a cells and ketone body utilization affects the balance of histone acetylation
physiological function
in the cytosol, acetoacetate is converted to acetoacetyl-CoA by acetoacetyl-CoA synthetase (AACS) for the synthesis of cholesterol and fatty acids. Acetoacetyl-CoA synthetase is a ketone body-utilizing enzyme, which is responsible for the synthesis of cholesterol and fatty acids from ketone bodies in lipogenic tissues, such as the liver and adipocytes. Enzyme AACS is posttranslationally regulated, being cleaved at a specific site in the kidney
physiological function
hydrodynamics-based gene transduction shows that overexpression of AACS (1547) increases the protein expression of caveolin-1, the principal component of the caveolae. Cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes
physiological function
-
acetoacetyl-CoA synthetase activity is required for growth of Streptomyces lividans on acetoacetate and is controlled by a protein acetyltransferase with unique domain organization
-
physiological function
-
AACS plays an important role in cholesterol homeostasis
-
physiological function
-
in the cytosol, acetoacetate is converted to acetoacetyl-CoA by acetoacetyl-CoA synthetase (AACS) for the synthesis of cholesterol and fatty acids. Acetoacetyl-CoA synthetase is a ketone body-utilizing enzyme, which is responsible for the synthesis of cholesterol and fatty acids from ketone bodies in lipogenic tissues, such as the liver and adipocytes. Enzyme AACS is posttranslationally regulated, being cleaved at a specific site in the kidney
-
additional information
-
transcription mechanism of AACS, expression of AACS is regulated by cholesterol depletion, overview
additional information
in addition to the two catalytic states, additional conformations are observed crystallographically that likely play a role in allowing access and egress of substrates and products from the relatively buried active site. The enzyme shows conformational flexibility. Structure-function analysis, overview. The C-terminal domain undergoes a large conformational change in the catalytic mechanism of acyl-CoA synthetases, the C-terminal extension is important for catalytic activity, structure comparisons. One region from the N-terminal domain interacts is the so-called P-loop, a glycine-, serine-, and threonine-rich region that interacts with the phosphates of ATP. This P-loop adopts multiple conformations in the different crystal structures and may play an important role in the release of PPi and trigger the conformational change. Specifically, the main chain carbonyls of Ser272, Gly274, and Gly277 form direct or water-mediated hydrogen bonds with Asn637 and Ser640. Asn637 also interacts directly with Arg183 and Asp187, while the carbonyl of Gly639 and the carbonyl and side chain oxygens of Ser640 interact with Ser184, Asp187, and Arg188.
additional information
site-specific cleavage at residue Asn547 of acetoacetyl-CoA synthetase by legumain, a lysosomal asparaginyl endopeptidase. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA
additional information
-
site-specific cleavage at residue Asn547 of acetoacetyl-CoA synthetase by legumain, a lysosomal asparaginyl endopeptidase. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA
additional information
-
in addition to the two catalytic states, additional conformations are observed crystallographically that likely play a role in allowing access and egress of substrates and products from the relatively buried active site. The enzyme shows conformational flexibility. Structure-function analysis, overview. The C-terminal domain undergoes a large conformational change in the catalytic mechanism of acyl-CoA synthetases, the C-terminal extension is important for catalytic activity, structure comparisons. One region from the N-terminal domain interacts is the so-called P-loop, a glycine-, serine-, and threonine-rich region that interacts with the phosphates of ATP. This P-loop adopts multiple conformations in the different crystal structures and may play an important role in the release of PPi and trigger the conformational change. Specifically, the main chain carbonyls of Ser272, Gly274, and Gly277 form direct or water-mediated hydrogen bonds with Asn637 and Ser640. Asn637 also interacts directly with Arg183 and Asp187, while the carbonyl of Gly639 and the carbonyl and side chain oxygens of Ser640 interact with Ser184, Asp187, and Arg188.
-
additional information
-
transcription mechanism of AACS, expression of AACS is regulated by cholesterol depletion, overview
-
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Ito, M.; Fukui, T.; Kamokari, M.; Saito, T.; Tomita, K.
Purification and characterization of acetoacetyl-CoA synthetase from rat liver
Biochim. Biophys. Acta
794
183-193
1984
Rattus norvegicus
brenda
Bergstrom, J.D.; Edmond, J.
Rat liver acetoacetyl-CoA synthetase
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110
3-9
1985
Rattus norvegicus
brenda
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Purification and characterization of acetoacetyl-CoA synthetase from Zoogloea ramigera 1-16-M
Eur. J. Biochem.
127
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1982
Zoogloea ramigera, Zoogloea ramigera 1-16-M / ATCC 19623
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Bergstrom, J.D.; Edmond, J.
A radiochemical assay for acetoacetyl-CoA synthetase
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149
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Homo sapiens, Rattus norvegicus, Zoogloea ramigera, Zoogloea ramigera 1-16-M / ATCC 19623
brenda
Stern, J.R.
A role of acetoacetyl-CoA synthetase in acetoacetate Utilization by rat liver cell fractions
Biochem. Biophys. Res. Commun.
44
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1971
Rattus norvegicus
brenda
Bergstrom, J.D.; Wong, G.A.; Edwards, P.A.; Edmond, J.
The regulation of acetoacetyl-CoA synthetase activity by modulators of cholesterol synthesis in vivo and the utilization of acetoacetate for cholesterogenesis
J. Biol. Chem.
259
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1984
Rattus norvegicus
brenda
Sato, H.; Takahashi, N.; Nakamoto, M.; Ohgami, M.; Yamazaki, M.; Fukui, T.
Effects of streptozotocin-induced diabetes on acetoacetyl-CoA synthetase activity in rats
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63
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2002
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Ohgami, M.; Takahashi, N.; Yamasaki, M.; Fukui, T.
Expression of acetoacetyl-CoA synthetase, a novel cytosolic ketone body-utilizing enzyme, in human brain
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65
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Homo sapiens (Q86V21), Homo sapiens
brenda
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Effects of development on acetoacetyl-CoA synthetase biosynthesis in rat liver
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22
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1999
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Iwahori, A.; Takahashi, N.; Nakamoto, M.; Iwama, M.; Fukui, T.
cDNA-derived amino acid sequence of acetoacetyl-CoA synthetase from rat liver
FEBS LETT.
466
239-243
2000
Rattus norvegicus, Rattus sp.
brenda
Cai, G.Q.; Driscoll, B.T.; Charles, T.C.
Requirement for the enzymes acetoacetyl coenzyme A synthetase and poly-3-hydroxybutyrate (PHB) synthase for growth of Sinorhizobium meliloti on PHB cycle intermediates
J. BACTERIOL.
182
2113-2118
2000
Sinorhizobium meliloti (Q9Z3R3), Sinorhizobium meliloti
brenda
Aneja, P.; Dziak, R.; Cai, G.Q.; Charles, T.C.
Identification of an acetoacetyl coenzyme A synthetase-dependent pathway for utilization of L-(+)-3-hydroxybutyrate in Sinorhizobium meliloti
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184
1571-1577
2002
Sinorhizobium meliloti
brenda
Yamasaki, M.; Hasegawa, S.; Suzuki, H.; Hidai, K.; Saitoh, Y.; Fukui, T.
Acetoacetyl-CoA synthetase gene is abundant in rat adipose, and related with fatty acid synthesis in mature adipocytes
Biochem. Biophys. Res. Commun.
335
215-219
2005
Rattus norvegicus
brenda
Ohnuki, M.; Takahashi, N.; Yamasaki, M.; Fukui, T.
Different localization in rat brain of the novel cytosolic ketone body-utilizing enzyme, acetoacetyl-CoA synthetase, as compared to succinyl-CoA:3-oxoacid CoA-transferase
Biochim. Biophys. Acta
1729
147-153
2005
Rattus norvegicus (Q9JMI1)
brenda
Yamasaki, M.; Hasegawa, S.; Kitani, T.; Hidai, K.; Fukui, T.
Differential effects of obesity on acetoacetyl-CoA synthetase gene in rat adipose tissues
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109
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2007
Rattus norvegicus
-
brenda
Harada, H.; Yu, F.; Okamoto, S.; Kuzuyama, T.; Utsumi, R.; Misawa, N.
Efficient synthesis of functional isoprenoids from acetoacetate through metabolic pathway-engineered Escherichia coli
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81
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Rattus norvegicus
brenda
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Transcriptional regulation of ketone body-utilizing enzyme, acetoacetyl-CoA synthetase, by C/EBPalpha during adipocyte differentiation
Biochim. Biophys. Acta
1779
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2008
Mus musculus
brenda
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Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma
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427
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2010
Homo sapiens
brenda
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Acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, is controlled by SREBP-2 and affects serum cholesterol levels
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107
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Mus musculus, Mus musculus ddY
brenda
Hasegawa, S.; Ikeda, Y.; Yamasaki, M.; Fukui, T.
The role of acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, in 3T3-L1 adipocyte differentiation
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35
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Mus musculus
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Acetoacetyl-CoA synthetase activity is controlled by a protein acetyltransferase with unique domain organization in Streptomyces lividans
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87
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Streptomyces lividans
brenda
Hasegawa, S.; Yamasaki, M.; Fukui, T.
Degradation of acetoacetyl-CoA synthetase, a ketone body-utilizing enzyme, by legumain in the mouse kidney
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453
631-635
2014
Mus musculus (Q9D2R0), Mus musculus, Mus musculus ddY (Q9D2R0)
brenda
Hasegawa, S.; Imai, M.; Yamasaki, M.; Takahashi, N.; Fukui, T.
Transcriptional regulation of acetoacetyl-CoA synthetase by Sp1 in neuroblastoma cells
Biochem. Biophys. Res. Commun.
495
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2018
Homo sapiens (Q86V21)
brenda
Hasegawa, S.; Inoue, D.; Yamasaki, M.; Li, C.; Imai, M.; Takahashi, N.; Fukui, T.
Site-specific cleavage of acetoacetyl-CoA synthetase by legumain
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Mus musculus (Q9D2R0), Mus musculus
brenda
McQualter, R.B.; Petrasovits, L.A.; Gebbie, L.K.; Schweitzer, D.; Blackman, D.M.; Chrysanthopoulos, P.; Hodson, M.P.; Plan, M.R.; Riches, J.D.; Snell, K.D.; Brumbley, S.M.; Nielsen, L.K.
The use of an acetoacetyl-CoA synthase in place of a beta-ketothiolase enhances poly-3-hydroxybutyrate production in sugarcane mesophyll cells
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13
700-707
2015
Streptomyces lividans (D6EQU8), Streptomyces lividans TK24 (D6EQU8)
brenda