Summary: Acetoacetate decarboxylase (ADC)

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Wikipedia: Acetoacetate decarboxylase
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This is the Wikipedia entry entitled "Acetoacetate decarboxylase". More...

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Acetoacetate decarboxylase Edit Wikipedia article

Acetoacetate decarboxylase

Acetoacetate decarboxylase dodecamer structure with bound 2-Pentanone bound in its active sites.

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles

Acetoacetate decarboxylase

Crystal structure of tetrameric acetoacetate decarboxylase from Chromobacterium violaceum.^[1]

Identifiers

Symbol

ADC

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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

		CO₂

[edit] 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.^[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:

[edit] Activity in humans and mammals

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.

[edit] 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.^[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]

[edit] References

^ 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.
^ 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.
^ ^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
^ IPR010451. Retrieved on 2007-05-05
^ Jones DT, Woods DR (1986). "Acetone-butanol fermentation revisited". Microbiol. Rev. 50 (4): 484–524. 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): 191–9. 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): 173–83. DOI:10.1016/0009-8981(76)90528-3. PMID 963888.
^ ^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.

[edit] External links

acetoacetate+decarboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 4.1.1.4
Brenda: Entry of Acetoacetate decarboxylase
KEGG: Entry of Acetoacetate decarboxylase
InterPro: IPR010451 Acetoacetate decarboxylase

Carbon-carbon lyases (EC 4.1)

4.1.1: Carboxy-lyases

4.1.2: Aldehyde-lyases

4.1.3: Oxo-acid-lyases

3-hydroxy-3-methylglutaryl-CoA lyase

4.1.99: Other

Tryptophanase

B
enzm
- 1.1
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- 15-18
2.1
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2.7.10
2.7.11-12
3.1
- 2
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3.1.3.48
3.4.21
- 22
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4.1
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5.1
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6.1-3
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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Acetoacetate decarboxylase (ADC) Provide feedback

This family consists of several acetoacetate decarboxylase (ADC) proteins ( EC:4.1.1.4).

Literature references

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

PANDIT:	PF06314
Pseudofam:	PF06314
SYSTERS:	ADC

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

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)

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 contains the following 2 members:

ADC DUF2071

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

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Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

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Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (72)	Full (670)	Representative proteomes				NCBI (644)	Meta (110)
	Seed (72)	Full (670)	RP15 (83)	RP35 (180)	RP55 (237)	RP75 (280)	NCBI (644)	Meta (110)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (72)	Full (670)	Representative proteomes				NCBI (644)	Meta (110)
	Seed (72)	Full (670)	RP15 (83)	RP35 (180)	RP55 (237)	RP75 (280)	NCBI (644)	Meta (110)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (72)	Full (670)	Representative proteomes				NCBI (644)	Meta (110)
	Seed (72)	Full (670)	RP15 (83)	RP35 (180)	RP55 (237)	RP75 (280)	NCBI (644)	Meta (110)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

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 %

HMM information

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

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

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order
family
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species

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As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Structures

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.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: ADC (PF06314)

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Summary: Acetoacetate decarboxylase (ADC)

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Acetoacetate decarboxylase Edit Wikipedia article

Contents

[edit] Activity in bacteria

[edit] Activity in humans and mammals

[edit] Clinical significance

[edit] References

[edit] External links

Acetoacetate decarboxylase (ADC) Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR010451

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Structures