Lipoprotein metabolism is a complex system of enzymes, receptors, and transport mechanisms, which may be thought of as three interconnected transport pathways. The exogenous pathway is responsible for the absorption and distribution of alimentary fat and the endogenous pathway for the production of cholesterol in the liver. The third pathway accomplishes the cholesterol transport to the peripheral tissue and the reverse cholesterol transport back to the liver for excretion.

Exogenous Pathway. Alimentary fats are taken up by intestinal enterocytes in the form of micelles and resynthesized to triglycerides and cholesteryl esters and incorporated into chylomicrons. Chylomicrons are then secreted in the portal circulation. In the capillaries of adipose tissue, heart, and skeletal muscle, triglycerides are removed from chylomicrons by the action of lipoprotein lipase, an enzyme located on the luminal side of the endothelial cells of these capillaries. The liberated fatty acids are rapidly taken up by adipose tissue or muscle cells by an insulin-dependent mechanism. In case of insulin resistance, free fatty acids increase in the blood and more free fatty acids are recirculated to the liver.

Endogenous Pathway. Through the above described process chylomicrons are depleted of triglycerides and this leaves two main residual particles of chylomicrons: a so-called chylomicron remnant and a precursor of HDL. The remnant particle is taken up by the liver and either used for synthesis of VLDL or excreted in the bile acid. In the fasting state, the liver synthesizes triglycerides as an energy source and secretes them as triglyceride-rich VLDL. Similar to the chylomicrons, the VLDL is depleted of triglycerides by the action of the endothelial lipoprotein lipase. The resultant VLDL remnants are called intermediate density lipoproteins (IDL). From IDL, the cholesterol-rich low density lipoproteins (LDL) are synthesized. LDL will eventually be removed from the circulation by the LDL receptor pathway in the liver and peripheral tissue. In addition, through a pathway that is less specific and less well understood, LDL can also be incorporated in atheromatose plaques.

Third Pathway. High density lipoproteins are synthesized in the liver and intestine and also in part by lipolysis of chylomicrons and VLDL. One of their functions is to remove cholesterol from the peripheral tissues and transport it to the liver for excretion. This cholesterol-lowering effect of HDL is considered atheroprotective.

Apolipoproteins. Apolipoproteins are important structural components of the lipoproteins and have important functions as activators and coactivators of many enzymatic pathways of the lipoprotein metabolism. The main apoprotein of HDL, the apolipoprotein A-I, for example, is an activator of the enzyme lecithin cholesterol acyltransferase, which catalyses the transfer of fatty acids from peripheral tissue into the HDL. A mutation of the LDL apolipoprotein, apo-B100, results in hypocholesterolemia because the mutant apoprotein can no longer mediate the binding of LDL to the LDL receptor.