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20  structures 525  species 0  interactions 670  sequences 12  architectures

Family: ADC (PF06314)

Summary: Acetoacetate decarboxylase (ADC)

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Acetoacetate decarboxylase Edit Wikipedia article

Acetoacetate decarboxylase
Acetoacetate decarboxylase biounit 3BH3 with inset.png
Acetoacetate decarboxylase dodecamer structure with bound 2-Pentanone bound in its active sites.
EC number
CAS number 9025-03-0
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Acetoacetate decarboxylase
Acetoacetate decarboxylase.png
Crystal structure of tetrameric acetoacetate decarboxylase from Chromobacterium violaceum.[1]
Symbol ADC
Pfam PF06314
Pfam clan CL0403
InterPro IPR010451

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.[2] In humans and other mammals, this reaction can take place spontaneously, or through the catalytic actions of acetoacetate decarboxylase.[3]

acetoacetic acid Acetoacetate decarboxylase acetone
Acetoacetic acid.png   Acetone-2D-skeletal.svg
Biochem reaction arrow forward NYNN horiz med.png

Activity in bacteria[edit]

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.[4] 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.[5]

Acetoacetate decarboxylase has been found and studied in the following bacteria:

Activity in humans and mammals[edit]

While this enzyme has not been purified from human tissue, the activity was shown to be present in human blood serum.[6][7]

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-β-hydroxybutyrate. Acetoacetate and D-β-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.[3]

Acetoacetate and D-β-hydroxybutyrate freely interconvert through the action of D-β-hydroxybutyrate dehydrogenase.[3] Subsequently, one function of acetoacetate decarboxylase may be to regulate the concentrations of the other, two 4-carbon ketone bodies.

Clinical significance[edit]

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.[8]

Under elevated levels of acetoacetate and D-β-hydroxybutyrate, acetoacetate decarboxylase produces significantly more acetone. Acetone is toxic, and can accumulate in the body under these conditions.[3] Elevated levels of acetone in the human breath can be used to diagnose diabetes.[8]


  1. ^ PDB 3BGT; Ho MC, Ménétret JF, Tsuruta H, Allen KN (May 2009). "The origin of the electrostatic perturbation in acetoacetate decarboxylase". Nature 459 (7245): 393–7. doi:10.1038/nature07938. PMID 19458715. 
  2. ^ 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): 41–6. doi:10.1021/bi9518306. PMID 8555196. 
  3. ^ a b c d 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
  4. ^ IPR010451. Retrieved on 2007-05-05
  5. ^ Jones DT, Woods DR (1986). "Acetone-butanol fermentation revisited". Microbiol. Rev. 50 (4): 484–524. PMC 373084. PMID 3540574. 
  6. ^ 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): 191–9. doi:10.1016/0009-8981(72)90316-6. PMID 4624981. 
  7. ^ 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): 173–83. doi:10.1016/0009-8981(76)90528-3. PMID 963888. 
  8. ^ a b 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): 115–23. doi:10.1089/dia.2005.7.115. PMID 15738709. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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This family consists of several acetoacetate decarboxylase (ADC) proteins ( EC:

Literature references

  1. 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

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].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ADC-like (CL0403), which has the following description:

Superfamily contains the acetoacetate decarboxylase enzyme family EC:, and a family of uncharacterized proteins from bacteria.

The clan contains the following 2 members:



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Seed source: Pfam-B_12720 (release 9.0)
Previous IDs: none
Type: Family
Author: Moxon SJ
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 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.8 29.8
Trusted cut-off 29.8 29.8
Noise cut-off 29.6 29.6
Model length: 236
Family (HMM) version: 6
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Species distribution

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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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