What initiates the formation of ketone bodies?

The formation of ketone bodies begins with the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA. This reaction is a crucial first step in the ketogenesis pathway, which occurs primarily in the liver during periods of low carbohydrate availability, such as fasting, prolonged exercise, or low-carb diets.

Acetyl-CoA is a key metabolic intermediate generated from the breakdown of fatty acids through beta-oxidation. When the concentration of acetyl-CoA increases, particularly when carbohydrate intake is low, the liver shifts its metabolic focus towards ketogenesis. By condensing two acetyl-CoA molecules, acetoacetyl-CoA is formed, setting the stage for the subsequent reactions that lead to the production of ketone bodies such as acetoacetate, β-hydroxybutyrate, and acetone.

This pathway is essential for providing an alternative energy source for various tissues, especially the brain, which can utilize ketone bodies in the absence of glucose. Thus, the condensation of acetyl-CoA to form acetoacetyl-CoA is a critical initiation point for ketone body synthesis.