|Molecular Weight:||27000-27500 Daltons (Da)|
|Taxa expressing:||Fungi, Nematoda, Metazoa, Fruit Fly, Arthropoda, Chordata, Mouse, Human, Eukaryota, Virus, Archae, Bacteria, Cyanobacteria, Green Plants|
|Pathway(s):||Propanoate Metabolism Pathway|
Acetic anhydride Acetopyruvate Acetylacetone Borohydride, Br-, Cl-, ClO4-, F-, HCN-, NO3-, SCN-
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|
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. 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.
Acetoacetate decarboxylase has been found and studied in the following bacteria:
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.
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
MDKYLSANSLEGVIDNEFSMPAPRWLNTYPAGPYRFINREFFIIAYETDPDLLQAILPPDMELLEPVVKFEFIRMPDSTGFGDYTESGQVVPVRYKGEEGGFTIS MFLDCHAPIAGGREIWGFPKKLAKPKLFVEEDTLIGILKYGSIDIAIATMGYKHRPLDAEKVLESVKKPVFLLKNIPNVDGTPLVNQLTKTYLTDITVKGAWTG PGSLELHPHALAPISNLYIKKIVSVSHFITDLTLPYGKVVADYLA 
atggacaagtatctttcagcaaattctctagaaggggttatcgataatgaatttagcatgccagctccacgttggttaaatacttacccggctggcccatatcggtttattaatcgtgaattttttat tattgcttatgaaaccgatccggatcttttgcaagctattttacctcctgatatggaattattggagccggtagtcaaatttgaatttatacgtatgcctgattcaacaggatttggtgattacaccg agtcagggcaagtggtccctgtgagatataaaggagaagagggcggatttaccatttcaatgtttcttgattgccatgctcctattgctggtggccgagaaatatggggttttccaaagaagc tggccaaacccaaattgtttgttgaagaagacacgctcattggcattcttaagtatgggagtattgatattgccatcgcaactatgggatataaacatcgtccgctggacgcggaaaaggtatt ggaatccgttaaaaagcctgtatttttacttaaaaacattcctaatgtagatggaactcctctagtgaatcagttgaccaagacttatttgactgatattacagtgaaaggagcatggaccgggc caggtagcttggagcttcatcctcatgcactggctcctatctctaatctttatattaaaaaaattgtatccgtttcacattttattactgatttgaccttaccgtatggaaaggttgttgccgattatctg gcctaa
- ↑ 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. PMID 8555196.
- ↑ 2.0 2.1 2.2 2.3 Nelson, David, and Michael Cox. Lehninger Principles of Biochemistry. 4th ed. New York: W.H. Freeman and Company, pp. 650-652, 2005. ISBN 0716743396
- ↑ InterPro IPR010451. Retrieved on 2007-05-05
- ↑ Jones DT, Woods DR (1986). "Acetone-butanol fermentation revisited". Microbiol. Rev. 50 (4): 484-524. PMID 3540574.
- ↑ 5.0 5.1 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. PMID 15738709.
- ↑ 6.0 6.1 GenomeNet ENZYME 22.214.171.124. Retrieved on 2007-05-05.
- MeSH acetoacetate+decarboxylase
- EC 126.96.36.199
- Brenda: Entry of Acetoacetate decarboxylase
- KEGG: Entry of Acetoacetate decarboxylase
- InterPro: IPR010451 Acetoacetate decarboxylase
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