Acetyl-coenzyme A transporter 1

Acetyl-coenzyme A transporter 1 (ACAT1), also known as thiolase, is a key enzyme involved in the metabolism of fatty acids. It is responsible for the transport of acetyl-CoA into the mitochondria, where it is used in the citric acid cycle to generate adenosine triphosphate (ATP), the main source of energy in cells.

Function

ACAT1 is a member of the carnitine/acylcarnitine translocase family. It is an integral membrane protein located in the mitochondrial inner membrane, where it facilitates the transport of acetyl-CoA from the cytosol into the mitochondrial matrix. This is a crucial step in the beta-oxidation of fatty acids, as acetyl-CoA is a key intermediate in this metabolic pathway.

Structure

The ACAT1 protein is composed of 621 amino acids and has a molecular weight of approximately 70 kDa. It contains six transmembrane domains, which form a channel for the transport of acetyl-CoA across the mitochondrial inner membrane. The protein also contains a catalytic site for the thiolase activity, which is located in the cytosolic domain of the protein.

Clinical significance

Mutations in the ACAT1 gene can lead to a rare metabolic disorder known as beta-ketothiolase deficiency. This condition is characterized by an inability to properly break down the amino acids isoleucine and methionine, leading to a buildup of harmful substances in the body. Symptoms can include metabolic acidosis, ketosis, and neurological problems.

See also

• Acetyl-CoA
• Beta-oxidation
• Mitochondria
• Beta-ketothiolase deficiency