| The integrated view of lipoprotein metabolism: the two pathways
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| The metabolism of chylomicrons and VLDL, from their assembly, through hydrolysis of triacylglycerols, to the formation and uptake of remnants, forms a major fuel distribution network in the body. Thus, it could be called the fuel transport pathway (Fig. 17.6). The fuel transport pathway is associated with the reverse cholesterol transport through component exchange.
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| The fuel transport pathway generates LDL as a byproduct of fuel distribution; further fate of LDL particles is not related to fuel supply. Therefore, the LDL metabolism, from the stage of remnants on, can be called 'the overflow pathway'. The concept of the two pathways is helpful in the understanding of atherogenesis, and the development of disorders of lipoprotein metabolism.
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| Figure 17.7 Reverse cholesterol transport. HDL are assembled in the liver and intestine as discoidal particles. They acquire cholesterol from cell membranes aided by cholesterol efflux regulatory protein (CERP). LCAT associated with HDL esterifies the acquired cholesterol. The formed cholesteryl esters move to the inside of the particle, and the particle becomes spherical. HDL exchanges apoproteins and cholesteryl esters with triacylglycerol-rich lipoproteins. This is facilitated by cholesterol ester transfer protein (CETP). HDL acquire triacylglycerols in exchange for cholesteryl esters. This increases their size further. However, when cholesterol transfer to the liver mediated by the scavenger receptor BI is completed, the HDL size decreases again: some of the redundant material is used to construct apoAI-rich, lipid-poor particles (pre-beta HDL). These re-enter the cholesterol removal cycle. |
| Pathway overload may result either from oversupply or from decreased degradation of a lipoprotein. Normally the apoE-containing remnants are quickly metabolized in the fuel
transport pathway and no excess LDL appear in the circulation. However, if dietary intake of cholesterol (or VLDL production) is high, or if there is a decrease in the number of apoB/E receptors, more LDL particles enter the overflow pathway.
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