Summary: Acetoacetate decarboxylase (ADC)
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Acetoacetate decarboxylase Edit Wikipedia article
|Acetoacetate decarboxylase dodecamer structure with bound 2-Pentanone bound in its active sites.|
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|Crystal structure of tetrameric acetoacetate decarboxylase from Chromobacterium violaceum.|
Acetoacetate decarboxylase (ADC) is an enzyme involved in both the ketone body production pathway in humans and other mammals, and solventogenesis in certain bacteria. Its reaction involves a decarboxylation of acetoacetate, forming acetone and carbon dioxide. The enzyme works in the cytosol of cells and demonstrates a maximum activity at pH 5.95. In humans and other mammals, this reaction can take place spontaneously, or through the catalytic actions of acetoacetate decarboxylase.
|acetoacetic acid||Acetoacetate decarboxylase||acetone|
 Activity in bacteria
In certain bacteria, acetoacetate decarboxylase is involved in solventogenesis, a process by which the butyric and acetic acid products of classical sugar fermentation are oxidized into acetone and butanol. The production of acetone by acetoacetate decarboxylase containing bacteria was utilized in large-scale industrial syntheses in the first half of the twentieth century. In the 1960s, the industry replaced this process with more efficient chemical syntheses of acetone.
Acetoacetate decarboxylase has been found and studied in the following bacteria:
- Bacillus polymyxa
- Chromobacterium violaceum
- Clostridium acetobutylicum
- Clostridium beijerinckii
- Clostridium cellulolyticum
- Pseudomonas putida
 Activity in humans and mammals
In humans and other mammals, the conversion of acetoacetate into acetone and carbon dioxide by acetoacetate decarboxylase is a final irreversible step in the ketone-body pathway that supplies the body with a secondary source of energy. In the liver, acetyl co-A formed from fats and lipids are transformed into three ketone bodies: acetone, acetoacetate, and D-?-hydroxybutyrate. Acetoacetate and D-?-hydroxybutyrate are exported to non-hepatic tissues, where they are converted back into acetyl-coA and used for fuel. Acetone and carbon dioxide on the other hand are exhaled, and not allowed to accumulate under normal conditions.
Acetoacetate and D-?-hydroxybutyrate freely interconvert through the action of D-?-hydroxybutyrate dehydrogenase. Subsequently, one function of acetoacetate decarboxylase may be to regulate the concentrations of the other, two 4-carbon ketone bodies.
 Clinical significance
Ketone body production increases significantly when the rate of glucose metabolism is insufficient in meeting the body's energy needs. Such conditions include high-fat ketogenic diets, diabetic ketoacidosis, or severe starvation.
Under elevated levels of acetoacetate and D-?-hydroxybutyrate, acetoacetate decarboxylase produces significantly more acetone. Acetone is toxic, and can accumulate in the body under these conditions. Elevated levels of acetone in the human breath can be used to diagnose diabetes.
- PDB 3BGT; Ho MC, Ménétret JF, Tsuruta H, Allen KN (May 2009). "The origin of the electrostatic perturbation in acetoacetate decarboxylase". Nature 459 (7245): 3937. DOI:10.1038/nature07938. PMID 19458715.
- Highbarger LA, Gerlt JA, Kenyon GL (1996). "Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of lysine 116 in determining the pKa of active-site lysine 115". Biochemistry 35 (1): 416. DOI:10.1021/bi9518306. PMID 8555196.
- Nelson, David, and Michael Cox. Lehninger Principles of Biochemistry. 4th ed. New York: W.H. Freeman and Company, pp. 650-652, 2005. ISBN 0-7167-4339-6
- IPR010451. Retrieved on 2007-05-05
- Jones DT, Woods DR (1986). "Acetone-butanol fermentation revisited". Microbiol. Rev. 50 (4): 484524. PMC 373084. PMID 3540574. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=373084.
- van Stekelenburg GJ, Koorevaar G (June 1972). "Evidence for the existence of mammalian acetoacetate decarboxylase: with special reference to human blood serum". Clin. Chim. Acta 39 (1): 1919. DOI:10.1016/0009-8981(72)90316-6. PMID 4624981.
- Koorevaar G, Van Stekelenburg GJ (September 1976). "Mammalian acetoacetate decarboxylase activity. Its distribution in subfractions of human albumin and occurrence in various tissues of the rat". Clin. Chim. Acta 71 (2): 17383. DOI:10.1016/0009-8981(76)90528-3. PMID 963888.
- Galassetti PR, Novak B, Nemet D, Rose-Gottron C, Cooper DM, Meinardi S, Newcomb R, Zaldivar F, Blake DR (2005). "Breath ethanol and acetone as indicators of serum glucose levels: an initial report". Diabetes Technol. Ther. 7 (1): 11523. DOI:10.1089/dia.2005.7.115. PMID 15738709.
- acetoacetate+decarboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 22.214.171.124
- Brenda: Entry of Acetoacetate decarboxylase
- KEGG: Entry of Acetoacetate decarboxylase
- InterPro: IPR010451 Acetoacetate decarboxylase
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Acetoacetate decarboxylase (ADC) Provide feedback
This family consists of several acetoacetate decarboxylase (ADC) proteins ( EC:126.96.36.199).
Gerischer U, Durre P; , J Bacteriol 1990;172:6907-6918.: Cloning, sequencing, and molecular analysis of the acetoacetate decarboxylase gene region from Clostridium acetobutylicum. PUBMED:2254264 EPMC:2254264
Internal database links
|Similarity to PfamA using HHSearch:||DUF2071|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR010451
Acetoacetate decarboxylase (ADC) is involved in solventogenesis in certain bacteria, which occurs at the end of the exponential growth phase when there is a metabolic switch from classical sugar fermentation with the production of acetate and butyrate to the re-internalisation and oxidation of these acids to acetate and butanol [PUBMED:11824611]. In Clostridium, SpoOA controls the switch from acid to solvent production. A SpoAO-binding motif occurs in the gene encoding ADC [PUBMED:10972834].
This family also contains the fungal decarboxylase DEC1 encoded by the Tox1B locus, which along with the Tox1A gene product is required for the production of the polyketide T-toxin. The pathogenic fungus Cochliobolus heterostrophus (Drechslera maydis) requires the T-toxin for high virulence to maize with T-cytoplasm [PUBMED:12236595].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||carboxy-lyase activity (GO:0016831)|
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|Seed source:||Pfam-B_12720 (release 9.0)|
|Number in seed:||72|
|Number in full:||670|
|Average length of the domain:||225.10 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||74.15 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||6|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ADC domain has been found. There are 20 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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