Acetoacetate decarboxylase

Protbox
Name=Acetoacetate Decarboxylase
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Molecular_weight=27000-27500 Daltons
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Taxa=Fungi, Nematoda, Metazoa, Fruit Fly, Arthropoda, Chordata, Mouse, Human, Eukaryota, Virus, Archae, Bacteria, Cyanobacteria, Green Plants
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Pathways= [http://www.genome.jp/dbget-bin/www_bget?enzyme+4.1.1.4 Propanoate Metabolism Pathway] [http://www.genome.jp/dbget-bin/show_pathway?map00072+4.1.1.4 Synthesis and Degradation of Ketone Bodies]
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Antagonists=2,4-Dinitrophenyl acetateAcetic anhydrideAcetopyruvateAcetylacetone Borohydride, Br-, Cl-, ClO4-, F-, HCN-, NO3-, SCN-
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ECnumber=4.1.1.4
CAS No.=9025-03-0
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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. [cite journal |author=Highbarger LA, Gerlt JA, Kenyon GL |title=Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of lysine 116 in determining the pKa of active-site lysine 115 |journal=Biochemistry |volume=35 |issue=1 |pages=41–6 |year=1996 |pmid=8555196 |doi=10.1021/bi9518306] In humans and other mammals, this reaction can take place spontaneously, or through the catalytic actions of acetoacetate decarboxylase.Nelson, David, and Michael Cox. "Lehninger Principles of Biochemistry". 4th ed. New York: W.H. Freeman and Company, pp. 650-652, 2005. ISBN 0716743396]

Enzymatic Reaction
foward_enzyme=Acetoacetate decarboxylase
reverse_enzyme=
substrate=acetoacetic acid
product=acetone
reaction_direction_(forward/reversible/reverse)=forward
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minor_foward_product(s)=CO₂
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Acetoacetate decarboxylase 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. [InterPro|IPR010451. Retrieved on 2007-05-05] 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 1960's, the industry replaced this process with more efficient chemical syntheses of acetone. [cite journal |author=Jones DT, Woods DR |title=Acetone-butanol fermentation revisited |journal=Microbiol. Rev. |volume=50 |issue=4 |pages=484–524 |year=1986 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=373084 |pmid=3540574]

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

"• Bacillus polymyxa
""• Clostridium acetobutylicum
""• Clostridium beijerinckii
""• Clostridium cellulolyticum
""• Pseudomonas putida"

Acetoacetate decarboxylase 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-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.

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

Acetoacetate decarboxylase and disease

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.cite journal |author=Galassetti PR, Novak B, Nemet D, Rose-Gottron C, Cooper DM, Meinardi S, Newcomb R, Zaldivar F, Blake DR |title=Breath ethanol and acetone as indicators of serum glucose levels: an initial report |journal=Diabetes Technol. Ther. |volume=7 |issue=1 |pages=115–23 |year=2005 |pmid=15738709 |doi=10.1089/dia.2005.7.115]

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. Elevated levels of acetone in the human breath can be used to diagnose diabetes.

Amino acid sequence

MDKYLSANSLEGVIDNEFSMPAPRWLNTYPAGPYRFINREFFIIAYETDPDLLQAILPPDMELLEPVVKFEFIRMPDSTGFGDYTESGQVVPVRYKGEEGGFTISMFLDCHAPIAGGREIWGFPKKLAKPKLFVEEDTLIGILKYGSIDIAIATMGYKHRPLDAEKVLESVKKPVFLLKNIPNVDGTPLVNQLTKTYLTDITVKGAWTGPGSLELHPHALAPISNLYIKKIVSVSHFITDLTLPYGKVVADYLA cite web |title=GenomeNet ENZYME 4.1.1.4 |url=http://www.genome.ad.jp/dbget-bin/www_bget?ec:4.1.1.4 |accessdate=2007-05-05]

Nucleotide sequence

atggacaagtatctttcagcaaattctctagaaggggttatcgataatgaatttagcatgccagctccacgttggttaaatacttacccggctggcccatatcggtttattaatcgtgaattttttattattgcttatgaaaccgatccggatcttttgcaagctattttacctcctgatatggaattattggagccggtagtcaaatttgaatttatacgtatgcctgattcaacaggatttggtgattacaccgagtcagggcaagtggtccctgtgagatataaaggagaagagggcggatttaccatttcaatgtttcttgattgccatgctcctattgctggtggccgagaaatatggggttttccaaagaagctggccaaacccaaattgtttgttgaagaagacacgctcattggcattcttaagtatgggagtattgatattgccatcgcaactatgggatataaacatcgtccgctggacgcggaaaaggtattggaatccgttaaaaagcctgtatttttacttaaaaacattcctaatgtagatggaactcctctagtgaatcagttgaccaagacttatttgactgatattacagtgaaaggagcatggaccgggccaggtagcttggagcttcatcctcatgcactggctcctatctctaatctttatattaaaaaaattgtatccgtttcacattttattactgatttgaccttaccgtatggaaaggttgttgccgattatctggcctaa

References

External links

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* [http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=4.1.1.4 Brenda: Entry of Acetoacetate decarboxylase]
* [http://www.genome.ad.jp/dbget-bin/www_bget?ko:K01574 KEGG: Entry of Acetoacetate decarboxylase]
* [http://www.ebi.ac.uk/interpro/IEntry?ac=IPR010451 InterPro: IPR010451 Acetoacetate decarboxylase]