Acetoacetate decarboxylase

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Acetoacetate Decarboxylase
Protein Structure/Function
Molecular Weight: 27000-27500 Daltons (Da)
Other
Taxa expressing: Fungi, Nematoda, Metazoa, Fruit Fly, Arthropoda, Chordata, Mouse, Human, Eukaryota, Virus, Archae, Bacteria, Cyanobacteria, Green Plants
Pathway(s): Propanoate Metabolism Pathway

Synthesis and Degradation of Ketone Bodies
Receptor/Ligand data
Antagonists: 2,4-Dinitrophenyl acetate

Acetic anhydride Acetopyruvate Acetylacetone Borohydride, Br-, Cl-, ClO4-, F-, HCN-, NO3-, SCN-
Database Links
EC number: 4.1.1.4

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

acetoacetic acid Acetoacetate decarboxylase acetone
 
CO2
 
 

Contents

[edit] 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.[3] 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.[4]

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

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

[edit] 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.[2]

Acetoacetate and D-β-hydroxybutyrate freely interconvert through the action of D-β-hydroxybutyrate dehydrogenase.[2] Subsequently, one function of acetoacetate decarboxylase may be to regulate the concentrations of the other, two 4-carbon ketone bodies.

[edit] 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.[5]

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.[2] Elevated levels of acetone in the human breath can be used to diagnose diabetes.[5]

[edit] Amino acid sequence

MDKYLSANSLEGVIDNEFSMPAPRWLNTYPAGPYRFINREFFIIAYETDPDLLQAILPPDMELLEPVVKFEFIRMPDSTGFGDYTESGQVVPVRYKGEEGGFTIS MFLDCHAPIAGGREIWGFPKKLAKPKLFVEEDTLIGILKYGSIDIAIATMGYKHRPLDAEKVLESVKKPVFLLKNIPNVDGTPLVNQLTKTYLTDITVKGAWTG PGSLELHPHALAPISNLYIKKIVSVSHFITDLTLPYGKVVADYLA [6]

[edit] Nucleotide sequence

atggacaagtatctttcagcaaattctctagaaggggttatcgataatgaatttagcatgccagctccacgttggttaaatacttacccggctggcccatatcggtttattaatcgtgaattttttat tattgcttatgaaaccgatccggatcttttgcaagctattttacctcctgatatggaattattggagccggtagtcaaatttgaatttatacgtatgcctgattcaacaggatttggtgattacaccg agtcagggcaagtggtccctgtgagatataaaggagaagagggcggatttaccatttcaatgtttcttgattgccatgctcctattgctggtggccgagaaatatggggttttccaaagaagc tggccaaacccaaattgtttgttgaagaagacacgctcattggcattcttaagtatgggagtattgatattgccatcgcaactatgggatataaacatcgtccgctggacgcggaaaaggtatt ggaatccgttaaaaagcctgtatttttacttaaaaacattcctaatgtagatggaactcctctagtgaatcagttgaccaagacttatttgactgatattacagtgaaaggagcatggaccgggc caggtagcttggagcttcatcctcatgcactggctcctatctctaatctttatattaaaaaaattgtatccgtttcacattttattactgatttgaccttaccgtatggaaaggttgttgccgattatctg gcctaa[6]

[edit] References

  1. ^ 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. 
  2. ^ 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 0716743396
  3. ^ IPR010451. Retrieved on 2007-05-05
  4. ^ Jones DT, Woods DR (1986). "Acetone-butanol fermentation revisited". Microbiol. Rev. 50 (4): 484–524. PMID 3540574. 
  5. ^ 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. 
  6. ^ a b GenomeNet ENZYME 4.1.1.4. Retrieved on 2007-05-05.

[edit] External links


v • d • e
Carbon-carbon lyases (EC 4.1)
4.1.1: Carboxy-lyases
4.1.2: Aldehyde-lyases
4.1.3: Oxo-acid-lyases