Acetoacetyl-CoA

Acetoacetyl-CoA is an important intermediate in the metabolism of fatty acids and ketone bodies. It is formed by the condensation of two molecules of acetyl-CoA and is involved in several metabolic pathways, including the ketogenesis and cholesterol synthesis pathways.

Formation

Acetoacetyl-CoA is synthesized from two molecules of acetyl-CoA by the enzyme thiolase. This reaction is a key step in the ketogenesis pathway, which occurs in the mitochondria of liver cells. The reaction can be summarized as follows:

2 Acetyl-CoA → Acetoacetyl-CoA + CoA-SH

Role in Metabolism

Acetoacetyl-CoA plays a crucial role in the metabolism of fatty acids and ketone bodies. It serves as a precursor for the synthesis of beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA), which is a key intermediate in the mevalonate pathway for cholesterol and isoprenoid synthesis. The conversion of acetoacetyl-CoA to HMG-CoA is catalyzed by the enzyme HMG-CoA synthase.

In the ketogenesis pathway, acetoacetyl-CoA is further converted to beta-hydroxybutyrate and acetoacetate, which are important ketone bodies used as energy sources by various tissues, especially during periods of fasting or carbohydrate restriction.

Clinical Significance

Abnormalities in the metabolism of acetoacetyl-CoA can lead to metabolic disorders. For example, defects in the enzymes involved in the ketogenesis pathway can result in conditions such as ketotic hypoglycemia and HMG-CoA lyase deficiency. These disorders can lead to an inability to properly produce and utilize ketone bodies, resulting in metabolic imbalances.

See Also

• Acetyl-CoA
• Ketogenesis
• Cholesterol synthesis
• Fatty acid metabolism
• HMG-CoA synthase
• Beta-hydroxybutyrate
• Acetoacetate