acetoacetyl-CoA (CHEBI:15345)

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CHEBI:15345 - acetoacetyl-CoA

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ChEBI Name	acetoacetyl-CoA

ChEBI ID	CHEBI:15345

Definition	A 3-oxoacyl-CoA that results from the formal condensation of the thiol group of coenzyme A with the carboxy group of acetoacetic acid.

Stars	This entity has been manually annotated by the ChEBI Team.

Secondary ChEBI IDs	CHEBI:41333, CHEBI:2392, CHEBI:11756, CHEBI:13706, CHEBI:22173

Supplier Information	ZINC000096014521

Download	Molfile XML SDF

more structures >>

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The Resolver thinks Mol

CAA - Ideal conformer

Mrv1927 06082115473D

starting HoverWatcher_5

Time for openFile(CAA - Ideal conformer

Mrv1927 06082115473D

94 96 0 0 0 0 999 V2000

5.0080 1.1060 -11.4150 N 0 0 0 0 0 0 0 0 0 0 0 0

4.0720 2.0300 -11.3010 C 0 0 0 0 0 0 0 0 0 0 0 0

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3.0200 0.9050 -9.5950 C 0 0 0 0 0 0 0 0 0 0 0 0

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5.0140 0.0320 -10.6320 C 0 0 0 0 0 0 0 0 0 0 0 0

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-0.6580 1.3080 -6.5020 C 0 0 2 0 0 0 0 0 0 0 0 0

0.7240 0.9910 -6.7390 O 0 0 0 0 0 0 0 0 0 0 0 0

-1.2400 0.3490 -5.4620 C 0 0 2 0 0 0 0 0 0 0 0 0

-0.5380 0.5030 -4.2270 O 0 0 0 0 0 0 0 0 0 0 0 0

-1.1990 -0.5290 -3.1840 P 0 0 1 0 0 5 0 0 0 0 0 0

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-0.5070 -2.3370 2.8990 C 0 0 2 0 0 0 0 0 0 0 0 0

-1.1280 -2.3500 1.5010 C 0 0 2 0 0 0 0 0 0 0 0 0

-0.6520 -0.9420 3.5090 C 0 0 0 0 0 0 0 0 0 0 0 0

0.9760 -2.6990 2.8010 C 0 0 0 0 0 0 0 0 0 0 0 0

-1.2240 -3.3580 3.7850 C 0 0 1 0 0 0 0 0 0 0 0 0

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-0.5340 -3.4330 5.1230 C 0 0 0 0 0 0 0 0 0 0 0 0

0.1580 -4.3900 5.3950 O 0 0 0 0 0 0 0 0 0 0 0 0

-0.6880 -2.4370 6.0170 N 0 0 0 0 0 0 0 0 0 0 0 0

-0.0020 -2.5000 7.3100 C 0 0 2 0 0 0 0 0 0 0 0 0

-0.3440 -1.2540 8.1310 C 0 0 2 0 0 0 0 0 0 0 0 0

0.3610 -1.3200 9.4610 C 0 0 0 0 0 0 0 0 0 0 0 0

1.0670 -2.2690 9.7260 O 0 0 0 0 0 0 0 0 0 0 0 0

0.2070 -0.3230 10.3550 N 0 0 0 0 0 0 0 0 0 0 0 0

0.8930 -0.3870 11.6480 C 0 0 2 0 0 0 0 0 0 0 0 0

0.5510 0.8580 12.4680 C 0 0 2 0 0 0 0 0 0 0 0 0

1.3980 0.7790 14.0660 S 0 0 0 0 0 0 0 0 0 0 0 0

0.8600 2.2480 14.7600 C 0 0 0 0 0 0 0 0 0 0 0 0

0.1110 2.9740 14.1400 O 0 0 0 0 0 0 0 0 0 0 0 0

1.3150 2.6400 16.1420 C 0 0 2 0 0 0 0 0 0 0 0 0

0.7030 3.9650 16.5170 C 0 0 0 0 0 0 0 0 0 0 0 0

-0.0270 4.5330 15.7410 O 0 0 0 0 0 0 0 0 0 0 0 0

1.0030 4.5810 17.8590 C 0 0 0 0 0 0 0 0 0 0 0 0

4.1050 2.8870 -11.9570 H 0 0 0 0 0 0 0 0 0 0 0 0

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0.2940 1.2170 -10.6420 H 0 0 0 0 0 0 0 0 0 0 0 0

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-5.2850 3.1780 -8.9820 H 0 0 0 0 0 0 0 0 0 0 0 0

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-2.2950 0.5750 -5.3100 H 0 0 0 0 0 0 0 0 0 0 0 0

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1.0790 -3.6940 2.3670 H 0 0 0 0 0 0 0 0 0 0 0 0

1.4860 -1.9720 2.1700 H 0 0 0 0 0 0 0 0 0 0 0 0

1.4180 -2.6900 3.7970 H 0 0 0 0 0 0 0 0 0 0 0 0

-2.2600 -3.0520 3.9270 H 0 0 0 0 0 0 0 0 0 0 0 0

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-1.2530 -1.6770 5.8050 H 0 0 0 0 0 0 0 0 0 0 0 0

1.0740 -2.5450 7.1490 H 0 0 0 0 0 0 0 0 0 0 0 0

-0.3260 -3.3900 7.8500 H 0 0 0 0 0 0 0 0 0 0 0 0

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1.9700 -0.4320 11.4860 H 0 0 0 0 0 0 0 0 0 0 0 0

0.5690 -1.2770 12.1870 H 0 0 0 0 0 0 0 0 0 0 0 0

-0.5250 0.9030 12.6300 H 0 0 0 0 0 0 0 0 0 0 0 0

0.8750 1.7480 11.9290 H 0 0 0 0 0 0 0 0 0 0 0 0

2.4020 2.7250 16.1560 H 0 0 0 0 0 0 0 0 0 0 0 0

1.0010 1.8790 16.8580 H 0 0 0 0 0 0 0 0 0 0 0 0

0.4750 5.5310 17.9490 H 0 0 0 0 0 0 0 0 0 0 0 0

0.6750 3.9070 18.6500 H 0 0 0 0 0 0 0 0 0 0 0 0

2.0750 4.7520 17.9490 H 0 0 0 0 0 0 0 0 0 0 0 0

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52 53 2 0 0 0 0

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54 92 1 0 0 0 0

54 93 1 0 0 0 0

54 94 1 0 0 0 0

M END): 24 ms

reading 94 atoms

ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false

1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them.

Default Van der Waals type for model set to Babel

94 atoms created

ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation

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Molfile expand

Wikipedia	License
Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver. In the ketone bodies digestion pathway (in the tissue), it is no longer associated with having HMG-CoA as a product or as a reactant. It is created from acetyl-CoA, a thioester, which reacts with the enolate of a second molecule of acetyl-CoA in a Claisen condensation reaction, and it is acted upon by HMG-CoA synthase to form HMG-CoA. During the metabolism of leucine, this last reaction is reversed. Some individuals may experience Acetoacetyl-CoA deficiency. This deficiency is classified as a disorder ketone body and isoleucine metabolism that can be inherited. Additional mutations include those with the enzymes within pathways related to Acetoacetyl CoA, including Beta-Ketothiolase deficiency and Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase mutation. Additionally, it reacts with NADPH-dependent acetoacetyl-coenzyme A reductase, also known as PhaB, in a pathway that produces polyester polyhydroxyalkanoate (PHA). The reduction of acetoacetyl-coA by Pha creates (R)-3-hydroxybutyryl-CoA, which polymerizes to PHA. The pathway is present in bacteria such as Ralstonia eutropha and the PCC6803 strain of Synechocystis. Mover over, Acetoacetyl-CoA is involved with neuronal development involving lipogenesis and providing fats and cholesterol for neuronal cells.
Read full article at Wikipedia

Formula

C25H40N7O18P3S

Net Charge

Average Mass

851.610

Monoisotopic Mass

851.13634

InChI

InChI=1S/C25H40N7O18P3S/c1-13(33)8-16(35)54-7-6-27-15(34)4-5-28-23(38)20(37)25(2,3)10-47-53(44,45)50-52(42,43)46-9-14-19(49-51(39,40)41)18(36)24(48-14)32-12-31-17-21(26)29-11-30-22(17)32/h11-12,14,18-20,24,36-37H,4-10H2,1-3H3,(H,27,34)(H,28,38)(H,42,43)(H,44,45)(H2,26,29,30)(H2,39,40,41)/t14-,18-,19-,20+,24-/m1/s1

InChIKey

OJFDKHTZOUZBOS-CITAKDKDSA-N

SMILES

CC(=O)CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)N1C=NC2=C1N=CN=C2N

Metabolite of Species	Details
Mus musculus (NCBI:txid10090)	Source: BioModels - MODEL1507180067 See: PubMed
Mus musculus (NCBI:txid10090)	From MetaboLights See: MetaboLights Study
Mus musculus (NCBI:txid10090)	From MetaboLights See: MetaboLights Study
Escherichia coli (NCBI:txid562)	See: PubMed

Roles Classification
Chemical Role(s):	acyl donor Any donor that can transfer acyl groups between molecular entities. (via acyl-CoA )

Biological Role(s):	Escherichia coli metabolite Any bacterial metabolite produced during a metabolic reaction in Escherichia coli. mouse metabolite Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).

View more via ChEBI Ontology

ChEBI Ontology
Outgoing	acetoacetyl-CoA (CHEBI:15345) has functional parent acetoacetic acid (CHEBI:15344) acetoacetyl-CoA (CHEBI:15345) has functional parent butyryl-CoA (CHEBI:15517) acetoacetyl-CoA (CHEBI:15345) has role Escherichia coli metabolite (CHEBI:76971) acetoacetyl-CoA (CHEBI:15345) has role mouse metabolite (CHEBI:75771) acetoacetyl-CoA (CHEBI:15345) is a 3-oxo-fatty acyl-CoA (CHEBI:15489) acetoacetyl-CoA (CHEBI:15345) is conjugate acid of acetoacetyl-CoA(4−) (CHEBI:57286)

Incoming	acetoacetyl-CoA(4−) (CHEBI:57286) is conjugate base of acetoacetyl-CoA (CHEBI:15345)

IUPAC Name

3'-phosphoadenosine 5'-{3-[(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-{[3-oxo-3-({2-[(3-oxobutanoyl)sulfanyl]ethyl}amino)propyl]amino}butyl] dihydrogen diphosphate}

Synonyms	Sources
3-Acetoacetyl-CoA	KEGG COMPOUND
acetoacetyl CoA	KNApSAcK
Acetoacetyl coenzyme A	KEGG COMPOUND
Acetoacetyl-CoA	KEGG COMPOUND
S-acetoacetyl-CoA	ChEBI
S-Acetoacetyl-coenzym A	ChEBI
S-acetoacetyl-coenzyme A	ChEBI

Manual Xrefs	Databases
Acetoacetyl-CoA	Wikipedia
C00007269	KNApSAcK
C00332	KEGG COMPOUND
c0229	UM-BBD
CAA	PDBeChem
DB03059	DrugBank
FDB022648	FooDB
HMDB0001484	HMDB
LMFA07050030	LIPID MAPS
View more database links

Registry Numbers	Types	Sources
1420-36-6	CAS Registry Number	KEGG COMPOUND
1420-36-6	CAS Registry Number	ChemIDplus
78273	Reaxys Registry Number	Reaxys

Citations

Liu L, Huber H, Berg IA (2020)
Enzymes Catalyzing Crotonyl-CoA Conversion to Acetoacetyl-CoA During the Autotrophic CO₂ Fixation in Metallosphaera sedula.
Frontiers in microbiology 11, 354 [PubMed:32218776]
[show Abstract]

Kasaragod P, Midekessa GB, Sridhar S, Schmitz W, Kiema TR, Hiltunen JK, Wierenga RK (2017)
Structural enzymology comparisons of multifunctional enzyme, type-1 (MFE1): the flexibility of its dehydrogenase part.
FEBS open bio 7, 1830-1842 [PubMed:29226071]
[show Abstract]

Harijan RK, Kiema TR, Syed SM, Qadir I, Mazet M, Bringaud F, Michels PAM, Wierenga RK (2017)
Crystallographic substrate binding studies of Leishmania mexicana SCP2-thiolase (type-2): unique features of oxyanion hole-1.
Protein engineering, design & selection : PEDS 30, 225-233 [PubMed:28062645]
[show Abstract]

Bock T, Kasten J, Müller R, Blankenfeldt W (2016)
Crystal Structure of the HMG-CoA Synthase MvaS from the Gram-Negative Bacterium Myxococcus xanthus.
Chembiochem : a European journal of chemical biology 17, 1257-1262 [PubMed:27124816]
[show Abstract]

Harijan RK, Mazet M, Kiema TR, Bouyssou G, Alexson SE, Bergmann U, Moreau P, Michels PA, Bringaud F, Wierenga RK (2016)
The SCP2-thiolase-like protein (SLP) of Trypanosoma brucei is an enzyme involved in lipid metabolism.
Proteins 84, 1075-1096 [PubMed:27093562]
[show Abstract]

Onwukwe GU, Koski MK, Pihko P, Schmitz W, Wierenga RK (2015)
Structures of yeast peroxisomal Δ(3),Δ(2)-enoyl-CoA isomerase complexed with acyl-CoA substrate analogues: the importance of hydrogen-bond networks for the reactivity of the catalytic base and the oxyanion hole.
Acta crystallographica. Section D, Biological crystallography 71, 2178-2191 [PubMed:26527136]
[show Abstract]

Kim J, Chang JH, Kim EJ, Kim KJ (2014)
Crystal structure of (R)-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha.
Biochemical and biophysical research communications 443, 783-788 [PubMed:24211201]
[show Abstract]

Mackenzie J, Pedersen L, Arent S, Henriksen A (2006)
Controlling electron transfer in Acyl-CoA oxidases and dehydrogenases: a structural view.
The Journal of biological chemistry 281, 31012-31020 [PubMed:16887802]
[show Abstract]

Kursula P, Ojala J, Lambeir AM, Wierenga RK (2002)
The catalytic cycle of biosynthetic thiolase: a conformational journey of an acetyl group through four binding modes and two oxyanion holes.
Biochemistry 41, 15543-15556 [PubMed:12501183]
[show Abstract]

Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ (2001)
Glutamate 170 of human l-3-hydroxyacyl-CoA dehydrogenase is required for proper orientation of the catalytic histidine and structural integrity of the enzyme.
The Journal of biological chemistry 276, 36718-36726 [PubMed:11451959]
[show Abstract]

Jez JM, Austin MB, Ferrer J, Bowman ME, Schröder J, Noel JP (2000)
Structural control of polyketide formation in plant-specific polyketide synthases.
Chemistry & biology 7, 919-930 [PubMed:11137815]
[show Abstract]

Background

Polyketide synthases (PKSs) generate molecular diversity by utilizing different starter molecules and by controlling the final length of the polyketide. Although exploitation of this mechanistic variability has produced novel polyketides, the structural foundation of this versatility is unclear. Plant-specific PKSs are essential for the biosynthesis of anti-microbial phytoalexins, anthocyanin floral pigments, and inducers of Rhizobium nodulation genes. 2-Pyrone synthase (2-PS) and chalcone synthase (CHS) are plant-specific PKSs that share 74% amino acid sequence identity. 2-PS forms the triketide methylpyrone from an acetyl-CoA starter molecule and two malonyl-CoAs. CHS uses a p-coumaroyl-CoA starter molecule and three malonyl-CoAs to produce the tetraketide chalcone. Our goal was to elucidate the molecular basis of starter molecule selectivity and control of polyketide length in this class of PKS.

Results

The 2.05 A resolution crystal structure of 2-PS complexed with the reaction intermediate acetoacetyl-CoA was determined by molecular replacement. 2-PS and CHS share a common three-dimensional fold, a set of conserved catalytic residues, and similar CoA binding sites. However, the active site cavity of 2-PS is smaller than the cavity in CHS. Of the 28 residues lining the 2-PS initiation/elongation cavity, four positions vary in CHS. Point mutations at three of these positions in CHS (T197L, G256L, and S338I) altered product formation. Combining these mutations in a CHS triple mutant (T197L/G256L/S338I) yielded an enzyme that was functionally identical to 2-PS.

Conclusions

Structural and functional characterization of 2-PS together with generation of a CHS mutant with an initiation/elongation cavity analogous to 2-PS demonstrates that cavity volume influences the choice of starter molecule and controls the final length of the polyketide. These results provide a structural basis for control of polyketide length in other PKSs, and suggest strategies for further increasing the scope of polyketide biosynthetic diversity.

Antonenkov VD, Croes K, Waelkens E, Van Veldhoven PP, Mannaerts GP (2000)
Identification, purification and characterization of an acetoacetyl-CoA thiolase from rat liver peroxisomes.
European journal of biochemistry 267, 2981-2990 [PubMed:10806397]
[show Abstract]

Djordjevic S, Pace CP, Stankovich MT, Kim JJ (1995)
Three-dimensional structure of butyryl-CoA dehydrogenase from Megasphaera elsdenii.
Biochemistry 34, 2163-2171 [PubMed:7857927]
[show Abstract]

Hovik R, Brodal B, Bartlett K, Osmundsen H (1991)
Metabolism of acetyl-CoA by isolated peroxisomal fractions: formation of acetate and acetoacetyl-CoA.
Journal of lipid research 32, 993-999 [PubMed:1682408]
[show Abstract]

Zołnierowicz S, Scisłowski PW, Swierczyński J, Zelewski L (1984)
Acetoacetate utilization by human placental mitochondria.
Placenta 5, 271-276 [PubMed:6150478]
[show Abstract]

Menahan LA, Hron WT, Hinkelman DG, Miziorko HM (1981)
Interrelationships between 3-hydroxy-3-methylglutaryl-CoA synthase, acetoacetyl-CoA and ketogenesis.
European journal of biochemistry 119, 287-294 [PubMed:6118268]
[show Abstract]

Takatori T, Imai Y (1975)
Studies on stereospecific reduction of acetoacetyl CoA and crotonyl CoA in lactating rabbit mammary glands.
The Tohoku journal of experimental medicine 116, 133-139 [PubMed:239468]
[show Abstract]

Last Modified

08 June 2021

CHEBI:15345 - acetoacetyl-CoA

Database

C

Background

Results

Conclusions

ChEBI is part of the ELIXIR infrastructure