Acetoacetate decarboxylase
![](/Images/godic/202412/14/Acetoacetate_decarboxylase_biounit_3BH3_with_inset0136.png")
![Crystal structure of acetoacetate decarboxylase in complex with an inhibitor, pentan-2-one. Using the residue Lys115, this inhibitor forms an acetyl acetone Schiff base intermediate. Mostly hydrophobic residues, such as Met 97 and Phe27, are found in the active site. This image was generated using PyMOL, from PDB ID 3BH3.[8]](/Images/godic/202412/14/AAD_active_site0136.png")
![Figure 1: General mechanism of acetoacetate decarboxylase, proceeding through a Schiff base intermediate and producing acetone and carbon dioxide [2]](/Images/godic/202412/14/AAD_final_mech0136.jpg")
![Figure 2: Scheme of the reaction, with reporter molecule 5-NSA, used by Westheimer et al. to measure the pKa of Lys115 in the active site.[11]](/Images/godic/202412/14/Reporter_molecule_scheme_Westheimer0136.jpg")
Acetoacetate decarboxylase (AAD or ADC) is an enzyme involved in both the ketone body production pathway in humans and other mammals, and solventogenesis in bacteria. Acetoacetate decarboxylase plays a key role in solvent production by catalyzing the decarboxylation of acetoacetate, yielding acetone and carbon dioxide. This enzyme has been of particular interest because it is a classic example of how pKa values of ionizable groups in the enzyme active site can be significantly perturbed. Specifically, the pKa value of lysine 115 in the active site is unusually low, allowing for the formation of a Schiff base intermediate and catalysis.