Acetoacetyl-CoA thiolase

Acetoacetyl-CoA thiolase (also known as acetyl-CoA acetyltransferase or AACT) is an enzyme that plays a significant role in lipid metabolism and the ketogenesis pathway. This enzyme catalyzes the Claisen condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA. The reaction is a key step in the biosynthesis of fatty acids and ketone bodies, making it crucial for energy production in organisms, especially during periods of fasting or low-carbohydrate diets.

Function

Acetoacetyl-CoA thiolase operates in both the synthesis and breakdown of ketone bodies. In the liver, it contributes to the production of ketone bodies through ketogenesis. These ketone bodies are then transported to other tissues, such as the brain and muscle, where they are converted back into acetyl-CoA to be used as an energy source. This enzyme is also involved in the mevalonate pathway, which is essential for the synthesis of cholesterol and isoprenoids.

Structure

The enzyme is a homotetramer in most organisms, meaning it is composed of four identical subunits. Each subunit contains an active site where the reaction occurs. The structure of acetoacetyl-CoA thiolase allows it to efficiently catalyze the condensation reaction, making it a vital component in metabolic pathways.

Genetic and Clinical Significance

Mutations in the gene encoding acetoacetyl-CoA thiolase can lead to metabolic disorders, including ketolysis deficiency and beta-ketothiolase deficiency. These conditions are characterized by an inability to properly utilize ketone bodies, leading to a buildup of toxic compounds in the body. Symptoms can include episodes of ketoacidosis, hypoglycemia, and vomiting. Early diagnosis and management are crucial for individuals affected by these disorders.

Pathway

Acetoacetyl-CoA thiolase is involved in several metabolic pathways:

• In ketogenesis, it catalyzes the first step, converting two molecules of acetyl-CoA into acetoacetyl-CoA.
• In the synthesis of fatty acids, it participates in the formation of acetoacetyl-CoA, which can be further converted into malonyl-CoA, a building block for fatty acid synthesis.
• It also plays a role in the mevalonate pathway for cholesterol and isoprenoid synthesis.

See Also

• Ketogenesis
• Lipid metabolism
• Fatty acid synthesis
• Mevalonate pathway

Acetoacetyl-CoA thiolase Resources
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