acetoacetate

Acetoacetate, also known as acetoacetate ion when deprotonated, is a four-carbon beta-keto carboxylate that serves as one of the ketone bodies produced during fatty acid oxidation. In physiological contexts it is mainly present in the blood and surrounding tissues in the form of its conjugate base or as its ketone body, acetoacetate, which can be interconverted with beta-hydroxybutyrate and acetone.

In human metabolism, acetoacetate is produced in the liver during ketogenesis. The process begins with the breakdown of HMG-CoA by HMG-CoA lyase, yielding acetoacetate and acetyl-CoA. Acetoacetate and beta-hydroxybutyrate then circulate to peripheral tissues, where acetoacetate can be activated to acetoacetyl-CoA by the enzyme succinyl-CoA:acetoacetate transferase (SCOT) using succinyl-CoA as the CoA donor. Thiolase subsequently splits acetoacetyl-CoA into two acetyl-CoA units that enter the citric acid cycle. Beta-hydroxybutyrate is produced from acetoacetate by reduction, and acetoacetate can be removed from circulation via decarboxylation to acetone.

Chemically, acetoacetate is an enolizable beta-keto acid and exists in equilibrium with its enol form. It can form salts such as sodium acetoacetate and can decarboxylate under certain conditions to yield acetone. Its biochemical role as a ketone body makes it a substrate for energy production during prolonged fasting, low-carbohydrate intake, or uncontrolled diabetes.

Clinically, ketone bodies including acetoacetate are monitored to assess metabolic state. Nitroprusside-based tests detect acetoacetate and acetone in urine or serum, but not beta-hydroxybutyrate, reflecting its relative abundance and reactivity in such assays.