Acetoacetate decarboxylase

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]

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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.^[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

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.

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]

Amino acid sequence

MDKYLSANSLEGVIDNEFSMPAPRWLNTYPAGPYRFINREFFIIAYETDPDLLQAILPPDMELLEPVVKFEFIRMPDSTGFGDYTESGQVVPVRYKGEEGGFTIS MFLDCHAPIAGGREIWGFPKKLAKPKLFVEEDTLIGILKYGSIDIAIATMGYKHRPLDAEKVLESVKKPVFLLKNIPNVDGTPLVNQLTKTYLTDITVKGAWTG PGSLELHPHALAPISNLYIKKIVSVSHFITDLTLPYGKVVADYLA ^[6]

Nucleotide sequence

atggacaagtatctttcagcaaattctctagaaggggttatcgataatgaatttagcatgccagctccacgttggttaaatacttacccggctggcccatatcggtttattaatcgtgaattttttat tattgcttatgaaaccgatccggatcttttgcaagctattttacctcctgatatggaattattggagccggtagtcaaatttgaatttatacgtatgcctgattcaacaggatttggtgattacaccg agtcagggcaagtggtccctgtgagatataaaggagaagagggcggatttaccatttcaatgtttcttgattgccatgctcctattgctggtggccgagaaatatggggttttccaaagaagc tggccaaacccaaattgtttgttgaagaagacacgctcattggcattcttaagtatgggagtattgatattgccatcgcaactatgggatataaacatcgtccgctggacgcggaaaaggtatt ggaatccgttaaaaagcctgtatttttacttaaaaacattcctaatgtagatggaactcctctagtgaatcagttgaccaagacttatttgactgatattacagtgaaaggagcatggaccgggc caggtagcttggagcttcatcctcatgcactggctcctatctctaatctttatattaaaaaaattgtatccgtttcacattttattactgatttgaccttaccgtatggaaaggttgttgccgattatctg gcctaa^[6]

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. 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. PMID 15738709.
6. ^ ^{a b} GenomeNet ENZYME 4.1.1.4. Retrieved on 2007-05-05.