Acetoacetic acid

Acetoacetic acid (IUPAC name: 3-oxobutanoic acid, also known as acetonecarboxylic acid or diacetic acid) is the organic compound with the formula CH3COCH2COOH. It is the simplest beta-keto acid, and like other members of this class, it is unstable. The methyl and ethyl esters, which are quite stable, are produced on a large scale industrially as precursors to dyes. Acetoacetic acid is a weak acid.

Biochemistry

Under typical physiological conditions, acetoacetic acid exists as its conjugate base, acetoacetate:

AcCH2CO2H → AcCH2CO−2 + H+

Unbound acetoacetate is primarily produced by liver mitochondria from its thioester with coenzyme A (CoA):

AcCH2C(O)−CoA + OH− → AcCH2CO−2 + H−CoA

The acetoacetyl-CoA itself is formed by three routes:

3-hydroxy-3-methylglutaryl CoA releases acetyl CoA and acetoacetate:

−O2CCH2−C(Me)(OH)−CH2C(O)−CoA → −O2CCH2−Ac + Ac−CoA

Acetoacetyl-CoA can come from beta oxidation of butyryl-CoA:

Et−CH2C(O)−CoA + 2NAD+ + H2O + FAD → Ac−CH2C(O)−CoA + 2NADH + FADH2

Condensation of pair of acetyl CoA molecules as catalyzed by thiolase.

2Ac−CoA → AcCH2C(O)−CoA + H−CoA

In mammals, acetoacetate produced in the liver (along with the other two "ketone bodies") is released into the bloodstream as an energy source during periods of fasting, exercise, or as a result of type 1 diabetes mellitus. First, a CoA group is enzymatically transferred to it from succinyl CoA, converting it back to acetoacetyl CoA; this is then broken into two acetyl CoA molecules by thiolase, and these then enter the citric acid cycle. Heart muscle and renal cortex prefer acetoacetate over glucose. The brain uses acetoacetate when glucose levels are low due to fasting or diabetes.

Synthesis and properties

Acetoacetic acid may be prepared by the hydrolysis of diketene. Its esters are produced analogously via reactions between diketene and alcohols, and acetoacetic acid can be prepared by the hydrolysis of these species.