Acetoacetate decarboxylase

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. Acetoacetate decarboxylase is an enzyme with major historical implications, specifically in World War I and in establishing the state of Israel. During the war the Allies needed pure acetone as a solvent for nitro-cellulose, a highly flammable compound that is the main component in gunpowder. In 1916, biochemist and future first president of Israel Chaim Weizmann was the first to isolate Clostridium acetobutylicum, a Gram-positive, anaerobic bacteria in which acetoacetate decarboxylase is found. Weizmann was able to harness the organism's ability to yield acetone from starch in order to mass-produce explosives during the war. This led the American and British governments to install the process devised by Chaim Weizmann in several large plants in England, France, Canada, and the United States. Through Weizmann's scientific contributions in World War I, he became close with influential British leaders educating them of his Zionist beliefs. One of them was Arthur Balfour, the man after whom the Balfour Declaration—the first document pronouncing British support in the establishment of a Jewish homeland—was named. The production of acetone by acetoacetate decarboxylase-containing or clostridial bacteria was utilized in large-scale industrial syntheses in the first half of the twentieth century. In the 1960s, the industry replaced this process with less expensive, more efficient chemical syntheses of acetone from petroleum and petroleum derivatives.