bodiesacetoacetate

Acetoacetate is a ketone body produced primarily in the liver during periods of fasting, prolonged exercise, or carbohydrate restriction, when fatty acids are mobilized for energy. It is one of the three circulating ketone bodies, the others being beta-hydroxybutyrate and acetone. Acetoacetate serves as an alternative energy substrate for many tissues, including the brain, heart, and skeletal muscle, during glucose scarcity.

Ketogenesis begins with the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA, catalyzed by thiolase. Acetoacetyl-CoA combines with another acetyl-CoA to form HMG-CoA via HMG-CoA synthase, and HMG-CoA lyase then cleaves HMG-CoA to yield acetoacetate and acetyl-CoA. In mitochondria, acetoacetate can be reduced to beta-hydroxybutyrate by beta-hydroxybutyrate dehydrogenase, using NADH, or it can spontaneously decarboxylate to acetone.

Once released into the bloodstream, acetoacetate is transported to peripheral tissues. There, succinyl-CoA: acetoacetate transferase (SCOT) converts acetoacetate to acetoacetyl-CoA, which is then split into two acetyl-CoA molecules that enter the citric acid cycle for energy production. The ratio of beta-hydroxybutyrate to acetoacetate in blood reflects the cellular redox state (NADH/NAD+).

Clinical relevance includes ketosis and ketoacidosis when ketone bodies accumulate excessively, such as in poorly controlled diabetes or prolonged starvation. Acetoacetate can be detected in urine or plasma; the nitroprusside test specifically detects acetoacetate. Under normal conditions, ketone bodies supplement energy production during fasting to help maintain metabolic stability.