The synthesis of ketone bodies occurs in the liver. The enzymes for ketone bodies synthesis are located in the mitochondrial matrix. Acetyl-CoA formed by oxidation of fatty acids, pyruvate, or some amino acids is the precursor for ketone bodies; ketogenesis occurs through the following reactions:

1. Two moles of acetyl-CoA condense to form acetoacetyl-CoA. This reaction is catalysed by thiolase, an enzyme involved in the final step of β-oxidation.
2. Acetoacetyl-CoA combines with water molecule of acetyl-CoA to produce β-hyroxy β-methyl glutaryl-CoA (HMG-CoA). HMG-CoA synthase catalyses this reaction and regulates the synthesis of ketone bodies.
3. HMG-CoA lyase cleaves HMG-CoA to produce acetoacetate and acetyl-CoA.
4. Acetoacetate can undergo spontaneous decarboxylation to form acetone.
5. Acetoacetate can be reduced by a dehydrogenase to hydroxybuyurate.