Sterol O-acyltransferase

Sterol O-acyltransferase (SOAT), also known as acyl-CoA:cholesterol acyltransferase (ACAT), is an enzyme crucial in the physiology and pathology of lipid metabolism. It catalyzes the formation of cholesteryl esters from cholesterol and fatty acyl-CoA. This reaction is fundamental in the process of lipid storage and transport. There are two known isoforms of the enzyme, SOAT1 and SOAT2, which have distinct tissue distributions and functions.

Function

SOAT plays a key role in the intracellular storage of cholesterol. By esterifying cholesterol, it facilitates the formation of lipid droplets, allowing cells to store excess cholesterol efficiently. This process is vital in cells that are involved in lipid transport and storage, such as adipocytes and hepatocytes. Moreover, SOAT activity is essential in the adrenal glands and ovaries, where cholesteryl esters are precursors for steroid hormone synthesis.

Isoforms

SOAT1

SOAT1 is ubiquitously expressed but is particularly abundant in the liver, adipose tissue, and adrenal glands. It is localized to the endoplasmic reticulum and is believed to play a key role in the systemic regulation of cholesterol levels.

SOAT2

SOAT2 is mainly found in the liver and intestines. It is thought to be involved in the assembly and secretion of apolipoprotein B-containing lipoproteins, such as very-low-density lipoprotein (VLDL) and chylomicrons. This isoform's activity influences the plasma levels of cholesterol and triglycerides, impacting cardiovascular health.

Clinical Significance

Abnormal SOAT activity is associated with various diseases, primarily those related to lipid metabolism disorders. Overactivity of SOAT can lead to the accumulation of cholesteryl esters, contributing to the development of atherosclerosis and cardiovascular disease. Inhibitors of SOAT are being explored as potential therapeutic agents for treating hypercholesterolemia and atherosclerosis.

Pharmacology

Several inhibitors of SOAT have been developed, aiming to reduce the risk of atherosclerosis by lowering intracellular cholesteryl ester formation and, consequently, circulating LDL cholesterol levels. These inhibitors vary in their specificity for SOAT1 and SOAT2, and their clinical efficacy and safety are subjects of ongoing research.

Genetics

The genes encoding SOAT1 and SOAT2 are located on different chromosomes. Mutations in these genes can affect enzyme activity and influence the risk of developing cardiovascular diseases. Genetic studies are exploring the relationship between SOAT gene variants and disease susceptibility, aiming to identify potential targets for therapeutic intervention.

See Also

• Lipid metabolism
• Cholesterol
• Atherosclerosis
• Hypercholesterolemia