Acyl-coenzyme A:cholesterol acyltransferase (ACAT)

Acyl-coenzyme A:cholesterol acyltransferase (ACAT), also known as sterol O-acyltransferase (SOAT), is a membrane-bound enzyme that catalyzes the intracellular esterification of cholesterol with long-chain fatty acyl-CoA to form cholesteryl esters. This reaction is crucial for cellular cholesterol homeostasis, as it allows excess free cholesterol to be stored in a less toxic, more inert form within cytoplasmic lipid droplets. There are two main isoenzymes in mammals: ACAT1 (SOAT1), expressed ubiquitously and involved in intracellular cholesterol homeostasis and foam cell formation, and ACAT2 (SOAT2), primarily localized to enterocytes and hepatocytes, playing a role in dietary cholesterol absorption and lipoprotein assembly. ACAT activity is critical for foam cell formation—a hallmark event during early atherosclerosis—by promoting accumulation of cholesteryl esters inside macrophages. Due to its central role in lipid metabolism, inhibiting ACAT has been explored therapeutically for cardiovascular disease prevention/treatment, Alzheimer’s Disease, and cancer.

Other names

Sterol O-acyltransferaseSOAT

ACAT inhibitors