Lipoprotein Metabolism Cycles

Exogenous Pathway of Lipid Metabolism

The exogenous metabolic pathway is concerned with the transport and utilisation of dietary fats.¹ After intestinal absorption, cholesterol and fatty acids from dietary fat are re-esterified to form triglycerides and cholesterol esters in intestinal mucosal cells. These molecules, together with bile acids, form water-soluble micelles that carry the lipid to absorptive sites in the duodenum. Following absorption in the duodenum, chylomicrons are formed which enter the bloodstream via intestinal lymphatics and the thoracic duct.

On entering the plasma, rapid changes take place in the chylomicron. It is hydrolysed by the enzyme lipoprotein (LP) lipase releasing the triglyceride core, free fatty acids and mono- and diglycerides for energy production or storage. The residual chylomicron undergoes further delipidation, resulting in the formation of chylomicron remnants. These are taken up by a number of tissues. In the liver they undergo lysosomal degradation, and are either used for a variety of purposes including remanufacture into new lipoproteins, production of cell membranes or excretion as bile salts.¹

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Endogenous Pathway of Lipid Metabolism

Whilst chylomicrons transport triglyceride from the gut to the liver, VLDL is the analogous particle that transports triglycerides from the liver to the rest of the body. Triglycerides together with cholesterol, cholesteryl ester and other lipids are transported in VLDL in the bloodstream, where VLDL undergoes delipidation with the enzyme lipoprotein lipase in a similar way to chylomicrons; this is the endogenous pathway of lipid metabolism. During this process, triglyceride is removed from the core and exchanged for cholesterol esters, principally from HDL. Whilst most VLDL is transformed into LDL, the larger VLDL particles are lipolysed to IDL, which is then removed from the plasma directly. Lipoprotein lipase is the main enzyme used in the lipolysis of large VLDL particles, whereas hepatic lipase reacts with the small VLDL and IDL particles.1 IDL is highly atherogenic.

The product of this metabolic cascade, LDL, exists in the plasma in the form of a number of subfractions; LDL I-IV. It has been shown that small dense LDL particles are the most atherogenic. They are absorbed by macrophages within the arterial wall to form lipid-rich foam cells, the initial stage in the pathogenesis of atherosclerotic plaques.¹

The enterohepatic circulation provides a route for the excretion of cholesterol and bile acids.¹

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Reverse Cholesterol Transport

As cholesterol cannot be broken down within the body, it is eliminated intact. It is transported via HDL from the peripheral tissues to be excreted by the liver. HDL begins as a lipid-deficient precursor which transforms into lipid-rich lipoprotein. In this form it transfers cholesterol either directly to the liver or to other circulating lipoproteins to be transported to the liver for elimination.¹

The observation that HDL acts as a vehicle for the transport of cholesterol for elimination has led to the identification of HDL as a protective factor against the development of atherosclerosis.¹

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Reference
1. In: Fast Facts - Hyperlipidaemia. Eds Durrington P, Sniderman A. Health Press Ltd, Oxford, 2000. 1–17.

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