What are cholesterol esters?

Cholesterol Esters: Structure, Function, and Metabolism

Cholesterol esters are hydrolyzable lipids formed by the esterification of cholesterol with long-chain fatty acids, primarily serving as storage and transport forms of cholesterol in the body. 1

Structure and Physical Properties

Cholesterol esters have a distinct structure consisting of:

• A cholesterol molecule covalently linked to a fatty acid via an ester bond
• Hydrophobic core components that make them more nonpolar than free cholesterol
• Hundreds to thousands of cholesterol ester molecules can be carried in the core of different lipoproteins 1

Physical characteristics include:

• More nonpolar than free cholesterol, making them ideal for storage and transport
• Ability to exist in crystal, liquid crystal, and liquid states depending on temperature 2
• Complex phase behavior that cannot be predicted from the individual properties of cholesterol and fatty acids 2

Biological Functions

Cholesterol esters serve several key functions in human physiology:

1. Transport of cholesterol:

   • Primary form for cholesterol transport in the bloodstream via lipoproteins 1
   • More efficient transport due to their ability to be packaged in larger amounts in lipoproteins 3

2. Storage of cholesterol:

   • Stored in intracellular lipid droplets 1, 3
   • Universal mechanism to store large quantities of cholesterol between organs and tissues 4
   • Helps avoid toxicity from excess cellular free cholesterol 4

3. Cholesterol homeostasis:

   • Play an active role in metabolic pathways that form the basis of cholesterol trafficking 5
   • Critical for maintaining appropriate cholesterol levels in cells and tissues 5

Metabolism and Transport

Cholesterol esters are integral to lipoprotein metabolism:

• Lipoprotein transport: Cholesterol esters are transported in the hydrophobic cores of lipoproteins including chylomicrons, VLDL, LDL, and HDL 1

• HDL metabolism: Within HDL, cholesterol is transported from the periphery to the liver, where it can be converted into bile acids, providing a mechanism to withdraw cholesterol from circulation 1

• Enzyme interactions:

  • Formation catalyzed by lecithin-cholesterol acyltransferase (LCAT) in plasma 1
  • Intracellular formation mediated by acyl-CoA:cholesterol acyltransferase (ACAT) 5

Clinical Significance

Cholesterol esters have important implications in several pathological conditions:

1. Atherosclerosis and cardiovascular disease:

   • Oxidized cholesterol esters (OxCEs) are major components of minimally and extensively oxidized LDL and of human atherosclerotic lesions 6
   • OxCEs can activate macrophages via toll-like receptor-4 (TLR4), inducing lipid accumulation and secretion of inflammatory cytokines 6

2. Dyslipidemia:

   • Abnormal cholesterol ester metabolism is associated with dyslipidemia, particularly in overweight and obesity 1
   • Elevated cholesterol esters in lipoproteins contribute to atherogenic patterns of dyslipidemia 1

3. Malignancy:

   • Tumor cells often show abnormal cholesterol metabolism with increased intracellular cholesterol esters 5
   • Alterations in cholesterol biosynthesis, uptake, esterification, and efflux contribute to this accumulation 5

Therapeutic Considerations

Several therapeutic approaches target cholesterol ester metabolism:

• Bile acid sequestrants: These medications can affect cholesterol ester metabolism by promoting cholesterol excretion 1

• Plant sterols/stanols: Compete with cholesterol for intestinal absorption, thus modulating cholesterol ester formation and total cholesterol levels 1, 7

• Targeting oxidized cholesterol esters: Specific inhibition of OxCE-induced TLR4 activation may offer novel treatments for atherosclerosis and cardiovascular disease 6

Understanding cholesterol esters and their metabolism provides important insights into lipid disorders and potential therapeutic targets for cardiovascular disease prevention and treatment.