6.2.1.16: acetoacetate-CoA ligase
This is an abbreviated version!
For detailed information about acetoacetate-CoA ligase, go to the full flat file.
Word Map on EC 6.2.1.16
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6.2.1.16
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ketone
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cholesterol
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lipogenesis
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body-utilizing
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lipogenic
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thiolase
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hmg-coa
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3-hydroxybutyrate
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coa-transferase
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cholestyramine
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zoogloea
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ramigera
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srebp-2
- 6.2.1.16
- ketone
- cholesterol
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lipogenesis
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body-utilizing
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lipogenic
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thiolase
- hmg-coa
- 3-hydroxybutyrate
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coa-transferase
- cholestyramine
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zoogloea
- ramigera
- srebp-2
Reaction
Synonyms
Aacl, AACS, Acetoacetate--CoA ligase, Acetoacetyl CoA synthetase, Acetoacetyl-CoA ligase, Acetoacetyl-CoA synthase, Acetoacetyl-CoA synthetase, Acetoacetyl-coenzyme A synthetase, acsA1, SlAacS, Synthetase, acetoacetyl coenzyme A
ECTree
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General Information
General Information on EC 6.2.1.16 - acetoacetate-CoA ligase
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malfunction
metabolism
physiological function
additional information
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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
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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
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Legumain is involved in the cleavage of AACS in the kidney, suggesting that AACS is degraded by the lysosomal pathway
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AACS plays an important role in cholesterol homeostasis
physiological function
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acetoacetyl-CoA synthetase activates ketone bodies and incorporates them into cholesterol and fatty acids in the cytosol of lipogenic tissue
physiological function
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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
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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
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acetoacetyl-CoA synthetase activity is required for growth of Streptomyces lividans on acetoacetate and is controlled by a protein acetyltransferase with unique domain organization
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physiological function
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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
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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
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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
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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.
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additional information
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transcription mechanism of AACS, expression of AACS is regulated by cholesterol depletion, overview
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