Citrate—CoA ligase

Citrate—CoA ligase (also known as ATP citrate lyase (ACL)) is an enzyme that plays a crucial role in cellular energy production and lipid metabolism. This enzyme catalyzes the conversion of citrate and Coenzyme A (CoA) into acetyl-CoA and oxaloacetate, a reaction that is essential for the synthesis of fatty acids and cholesterol in the cytosol. Acetyl-CoA is a key metabolic intermediate, serving as a building block for several biosynthetic pathways.

Function

Citrate—CoA ligase is primarily involved in the metabolic pathway that converts carbohydrates into fats. The enzyme is located in the cytosol, where it facilitates the production of acetyl-CoA from citrate, a compound that is transported out of the mitochondria. Acetyl-CoA is then used as a substrate for fatty acid synthesis and the production of cholesterol, which are vital components of cell membranes and precursors to steroid hormones.

Structure

The enzyme is a multimeric protein, typically composed of multiple subunits that work together to catalyze the reaction. The structure of Citrate—CoA ligase includes domains for binding ATP, citrate, and CoA, and its activity is regulated by the availability of these substrates and by the energy needs of the cell.

Clinical Significance

Inhibition of Citrate—CoA ligase has been explored as a therapeutic approach to treat metabolic disorders, such as obesity and type 2 diabetes, by reducing the synthesis of fatty acids and cholesterol. Additionally, because cancer cells often have altered energy metabolism, targeting this enzyme could potentially hinder the growth of certain tumors.

Pharmacology

Several inhibitors of Citrate—CoA ligase have been identified, which could serve as potential drugs for treating metabolic diseases or cancer. These inhibitors work by binding to the enzyme and preventing it from converting citrate to acetyl-CoA, thereby reducing the synthesis of fats and cholesterol.

See Also

• Acetyl-CoA
• Fatty acid synthesis
• Cholesterol synthesis
• Metabolic pathway
• Enzyme inhibitor