Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and the spontaneous breakdown product of acetoacetate, acetone) containing the ketone group that are produced by the liver from fatty acids. Ketone bodies are readily transported into tissues outside the liver and converted into acetyl-CoA, which then enters the citric acid cycle and is oxidized in the mitochondria for energy. 2 Acetyl-CoA is catalyzed by acetyl-CoA acetyltransferase homolog, mitochondrial to produce CoA and acetoacetyl-CoA. This is a bi-directional reaction occurring in the mitochondrion. Acetyl-CoA is also produced through the process of glycolysis outside of the mitochondrion. 3-Hydroxy-3-methylglutaryl-CoA and CoA are catalyzed by hydroxymethylglutaryl-CoA synthase to produce acetoacetyl-CoA, H2O, and acetyl-CoA. This is also a bi-directional reaction outside the mitochondrion. Additionally, acetoacetyl-CoA is a product of pyruvate metabolism and is involved in the separate process of fatty acid degradation. 3-Hydroxy-3-methylglutaryl-CoA is catalyzed by a uncharacterized protein outside of the mitochondrion and will produce acetoacetic acid (acetoacetate) and acetyl-CoA. Another bi-directional reaction occurring in the mitochondrion is succinyl-CoA and acetoacetic acid (acetoacetate) catalyzed by probable succinyl-CoA:3-ketoacid coenzyme A transferase, mitochondrial and producing acetoacetyl-CoA, and succinic acid (succinate). Acetoacetic acid is also produced through butanoate metabolism outside of the mitochondrion.

Ketone Body Metabolism References