Lipoproteins are complexes of lipids and proteins that transport hydrophobic lipids through the aqueous environment of the bloodstream. They consist of a hydrophobic core of triacylglycerols and cholesteryl esters surrounded by a hydrophilic shell of phospholipids, free cholesterol, and proteins called apolipoproteins.
Lipoprotein Classification
Lipoproteins are classified by density, which reflects their lipid-to-protein ratio. Chylomicrons are the largest and least dense, transporting dietary lipids from the intestine. Very low-density lipoproteins (VLDL) carry endogenously synthesized triacylglycerols from the liver. Intermediate-density lipoproteins (IDL) are VLDL remnants formed after triacylglycerol removal. Low-density lipoproteins (LDL) are cholesterol-rich particles derived from further VLDL metabolism. High-density lipoproteins (HDL) are the smallest and densest, involved in reverse cholesterol transport.
Apolipoproteins
Apolipoproteins serve as structural components, cofactors for enzymes, and ligands for receptors. ApoB-48 is the essential structural protein of chylomicrons, while apoB-100 is found on VLDL, IDL, and LDL. ApoC-II activates lipoprotein lipase, and apoE mediates the hepatic uptake of remnant particles. ApoA-I is the main protein of HDL and activates lecithin-cholesterol acyltransferase.
The Exogenous Pathway
Dietary lipids are absorbed by enterocytes, incorporated into chylomicrons, and secreted into the lymphatic system. Chylomicrons enter the bloodstream and interact with lipoprotein lipase on capillary endothelial surfaces of adipose tissue and muscle. Lipoprotein lipase, activated by apoC-II, hydrolyzes triacylglycerols, releasing free fatty acids for uptake by tissues and subsequent fatty acid oxidation and synthesis. The resulting chylomicron remnants are cleared by the liver via apoE-mediated receptor binding.
The Endogenous Pathway
The liver secretes VLDL, which transports endogenously synthesized triacylglycerols. As VLDL circulates, lipoprotein lipase hydrolyzes its triacylglycerol content, converting VLDL to IDL. IDL can be taken up by the liver or further processed by hepatic lipase to form LDL. LDL is the primary cholesterol-carrying particle in the blood and delivers cholesterol to peripheral tissues via the LDL receptor. Cells regulate their cholesterol uptake by modulating LDL receptor expression.
Reverse Cholesterol Transport
HDL plays a central role in reverse cholesterol transport, removing excess cholesterol from peripheral tissues and delivering it to the liver for excretion or reutilization. Nascent, disk-shaped HDL particles are produced by the liver and intestine. They acquire cholesterol from cells via the ABCA1 transporter, and the enzyme lecithin-cholesterol acyltransferase esterifies the cholesterol, converting HDL to a spherical, mature form. HDL cholesterol can be transferred to LDL and VLDL by cholesteryl ester transfer protein, or delivered directly to the liver via the SR-BI receptor.
Clinical Significance
High LDL cholesterol is a major risk factor for atherosclerosis and cardiovascular disease, while HDL cholesterol is considered protective. Elevated triglycerides are associated with increased cardiovascular risk and can signal metabolic disorders. Lipid profiles routinely measure total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides to assess cardiovascular risk. Statins lower LDL by inhibiting HMG-CoA reductase, while fibrates target triglycerides and HDL.
