Ketogenesis is the synthesis of ketone bodies. Three are 3 ketone bodies namely, acetoacetate, β-hydroxybutyrate, and acetone. Normally in our body, a very less amount of ketone bodies are present in our blood as the starting material for ketogenesis is acetyl-CoA which enters the TCA cycle. When there is the excess formation of acetyl CoA from β-oxidation, It undergoes ketogenesis in the mitochondria of the liver. There are 2 conditions that generate more ketone bodies by excessive lipolysis which are prolonged starvation and uncontrolled diabetes mellitus. Our body completely depends upon ketone bodies for energy during these 2 conditions. The first step of ketogenesis is a condensation of two molecules of acetyl CoA to form acetoacetyl CoA, catalyzed by an enzyme thiolase. In the second step of the ketogenesis pathway, another molecule of acetyl CoA reacts with the acetoacetyl CoA to form 3-Hydroxy-3-methyl glutaryl CoA (HMGCoA). This reaction is catalyzed by the HMG-CoA synthase enzyme that is the rate-limiting enzyme. The HMG-CoA converted to acetoacetate by the action of the enzyme HMG-CoA lyase. The acetoacetate is spontaneously decarboxylated to acetone. Acetoacetate also can be reversibly converted to β-hydroxybutyrate by a β-hydroxybutyrate dehydrogenase enzyme.
Utilization of ketone bodies