Cholesterol Esters: Function & Diseases

Cholesterol esters are cholesterol molecules esterified with fatty acids. They represent a transport form of cholesterol that is found in up to 75 percent of the blood. Esterified cholesterol is more easily broken down in the liver than unesterified cholesterol.

What is cholesterol ester?

Cholesteryl ester represents a cholesterol molecule esterified with fatty acids. Cholesterol is a polycyclic alcohol to whose hydroxyl group a fatty acid molecule attaches with the help of an enzyme, splitting off water. The cholesterol ester is a transport form of cholesterol which, as an ester, can also be broken down more easily in the liver. In the body, 75 percent of cholesterol occurs as cholesterol ester. It serves as an intermediate product and storage substance in the organism’s metabolism. That is why it is also an intrinsic part of the human diet. Cholesterol esters are mainly found in animal food products. The most common fatty acids found in cholesterol esters are oleic acid, palm acid and linoleic acid. The enzyme lecithin-cholesterol acyltransferase is responsible for the esterification of cholesterol. This enzyme is located in the HDL particles and also controls the esterification of cholesterol there. The HDL particles consist of cholesterol, triglycerides and lipoproteins. Bound to the lipoproteins, the water-insoluble cholesterol esters are made transportable and transported from the organs to the liver via the HDL particles. Esterification causes the density of these particles to increase, so they are considered high-density lipoproteins.

Function, effects, and roles

Cholesterol esters represent only one transport form of cholesterol. They are bound to lipoproteins in HDL, LDL, or VLDL. Thus, cholesterol occurs both free and esterified with fatty acids. However, esterified cholesterol is more easily broken down by the liver. It can be transported very well in the blood with the help of lipoproteins. Its formation takes place in the high-density lipoproteins. These are highly concentrated lipoproteins. The HDL transport cholesterol from the extrahepatic organs (organs located outside the liver) to the liver, where it is then broken down into bile acids. In the process, the bile acids are excreted into the intestines via the bile and at the same time emulsify the fats, cholesterol and cholesterol esters absorbed from the diet. More than 90 percent of the cholesterol converted into bile acid is converted back and enters the circulation again. Cholesterol and cholesterol esters are starting materials for the formation of hormones such as sex hormones, mineral corticoids and glucocorticoids (cortisone). Furthermore, they serve for the formation of bile acids and vitamin D.

Formation, occurrence, properties, and optimal levels

Cholesterol esters are formed in the HDL with the help of the enzyme lecithin-cholesterol acyltransferase. The HDL or high-density lipoproteins are responsible for transporting cholesterol from the tissues of the body to the liver. This transport is also known as reverse cholesterol transport. In the liver, the esterified cholesterol can be well broken down. However, from the HDL, the cholesterol esters can also be transferred to the LDL or VLDL with exchange with triglycerides. Therefore, cholesterol esters are also found in the LDL and VLDL. Generally, HDL is called good cholesterol because it transports cholesterol located in the tissues to the liver for degradation. It has been found that the risk of developing arteriosclerosis and cardiovascular disorders is lower with a high HDL concentration. In some cases, a slight regression of atherosclerotic changes has even been observed. For the degradation of cholesterol in the liver, it is first necessary to break the ester bond between cholesterol and fatty acid. This requires a hormone-sensitive lipase. The cholesterol esters ingested with food are broken down into their individual components by a bile salt-activated lipase. This releases both the fatty acids and the cholesterol. Within a cell, free cholesterol is also esterified by the so-called sterol O-acyltransferase and converted into its storage form as cholesterol ester. Thus, undesirable effects due to free cholesterol are avoided in the cytosol. However, accumulations of cholesterol esters in macrophages or smooth muscle indicate the onset of arteriosclerosis.

Diseases and disorders

A balance is formed in cells between cholesterol synthesis and release from cholesterol esters. The breakdown of cholesterol esters is accomplished by a process called acid lipase. There are two very rare clinical pictures that are associated with the loss of function or reduced activity of acid lipase. For example, a genetic defect on chromosome 10 affects a gene that encodes acid lipase. In the case of complete loss of this enzyme, cholesterol esters can no longer be broken down in the lysosomes. The result is a reduced concentration of cholesterol in the cytoplasm of the cell. This interrupts the control loop and leads to an uncontrolled production of cholesterol. This also increases LDL receptor activity. The cell is now overloaded with cholesterol, which eventually leads to cell death. This disease is usually fatal in early infancy (at the age of three to six months). A much milder form of the disease is cholesterol ester storage disease (CEST). Here, too, the same gene is affected. However, acid lipase still has a residual function here, so that the disease only affects the liver. This residual function means that cholesterol ester degradation can still take place in most cells. However, due to the high metabolic activity in the liver, the slowed degradation has an effect there. Thus, increased concentrations of cholesterol esters are stored in the liver. The disease usually becomes apparent after the age of 18, with an enlarged liver and an increased risk of developing atherosclerosis.