Acetoacetic acid ( IUPAC name: 3-oxobutanoic acid, also known as acetonecarboxylic acid or diacetic acid) is the

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula CH₃COCH₂COOH. It is the simplest beta- keto acid, and like other members of this class, it is unstable. The

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

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 A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the reve ...

, acetoacetate: : Unbound acetoacetate is primarily produced by

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

from its

thioester In organic chemistry, thioesters are organosulfur compounds with the molecular structure . They are analogous to carboxylate esters () with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix ...

with

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

(CoA): : The acetoacetyl-CoA itself is formed by three routes: *

3-hydroxy-3-methylglutaryl CoA β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate pathway, mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase ...

releases acetyl CoA and acetoacetate: *: *Acetoacetyl-CoA can come from

beta oxidation In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enter ...

of butyryl-CoA: *: *Condensation of pair of acetyl CoA molecules as catalyzed by thiolase. *: 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 Fasting is the act of refraining from eating, and sometimes drinking. However, from a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (before "breakfast"), or to the metabolic sta ...

, 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 The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of chemical reaction, biochemical reactions that release the energy stored in nutrients through acetyl-Co ...

. 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. In general, acetoacetic acid is generated at 0 °C and used in situ immediately. It decomposes at a moderate

reaction rate The reaction rate or rate of reaction is the speed at which a chemical reaction takes place, defined as proportional to the increase in the concentration of a product per unit time and to the decrease in the concentration of a reactant per u ...

into

acetone Acetone (2-propanone or dimethyl ketone) is an organic compound with the chemical formula, formula . It is the simplest and smallest ketone (). It is a colorless, highly Volatile organic compound, volatile, and flammable liquid with a charact ...

and

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

: : The acid form has a

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

of 140 minutes at 37 °C in water, whereas the basic form (the anion) has a half-life of 130 hours. That is, it reacts about 55 times more slowly. The corresponding decarboxylation of trifluoroacetoacetate is used to prepare trifluoroacetone: : It is a weak acid (like most alkyl carboxylic acids), with a p''K''_a of 3.58. Acetoacetic acid displays keto-enol tautomerisation, with the enol form being partially stabilised by extended conjugation and intramolecular H-bonding. The equilibrium is strongly solvent depended; with the keto form dominating in polar solvents (98% in water) and the enol form accounting for 25-49% of material in non-polar solvents. 3-Oxobutyric acid KetoEnol

Applications

Acetoacetic esters are used for the acetoacetylation reaction, which is widely used in the production of

arylide yellow Arylide yellow, also known as Hansa yellow and monoazo yellow, is a family of organic compounds used as pigments. They are primarily used as industrial colorants including plastics, building paints and inks. They are also used in artistic oil pai ...

s and diarylide dyes. Although the esters can be used in this reaction, diketene also reacts with

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

s and

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s to the corresponding acetoacetic acid derivatives in a process called acetoacetylation. An example is the reaction with 4-amino indane:

Detection

Acetoacetic acid is measured in the urine of people with diabetes to test for ketoacidosis and for monitoring people on a

ketogenic Ketogenesis is the biochemistry, biochemical process through which organisms produce ketone bodies by fatty acid metabolism, breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the bra ...

low-carbohydrate diet Low-carbohydrate diets restrict carbohydrate consumption relative to the average diet (nutrition), diet. Foods high in carbohydrates (e.g., sugar, bread, pasta) are limited, and replaced with foods containing a higher percentage of fat and pro ...

. This is done using dipsticks coated in nitroprusside or similar reagents. Nitroprusside changes from pink to purple in the presence of acetoacetate, the

of acetoacetic acid, and the colour change is graded by eye. The test does not measure β-hydroxybutyrate, the most abundant ketone in the body; during treatment of ketoacidosis β-hydroxybutyrate is converted to acetoacetate so the test is not useful after treatment begins and may be falsely low at diagnosis. Similar tests are used in

dairy cows Dairy cattle (also called dairy cows) are cattle bred with the ability to produce large quantities of milk, from which dairy products are made. Dairy cattle generally are of the species '' Bos taurus''. Historically, little distinction was ...

to test for

ketosis Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability. In physiological ketosis, ketones in the blood are elevated above bas ...

References

{{HDAC inhibitors Histone deacetylase inhibitors Beta-keto acids

Biochemistry

Synthesis and properties

Applications

Detection

See also

References