ATP citrate lyase

ATP citrate lyase (ACL) is an enzyme that plays a key role in the metabolism of fatty acids and cholesterol. It is a crucial enzyme in the cytosol of cells where it catalyzes the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, along with the hydrolysis of ATP.

Function

ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer of apparently identical subunits. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine.

Clinical significance

Several studies have indicated that ACL is a potential target for cancer therapies. It has been shown that human cancers, including lung cancer, breast cancer, and prostate cancer, have increased levels of ACL. Inhibitors of ACL may have therapeutic potential in hyperlipidemia and obesity.

Inhibitors

Several ATP citrate lyase inhibitors have been developed for clinical use, including bempedoic acid and etomoxir. These drugs are used to treat conditions such as high cholesterol and type 2 diabetes.

See also

• Citric acid cycle
• Lipogenesis
• Cholesterol