Endogenous lipoproteins pathway

The rationale for this type of contrast agent is to use the endogenous metabolic pathway of lipid metabolism in the liver for the transport of iodinated substances. Chylomicron remnants are naturally occurring lipoproteins in the blood that are responsible for the transport of lipids into the liver. Three different mechanisms for this transport are discussed direct uptake by the low-density lipoprotein receptor transport to the low-density lipoprotein receptor-related protein (LRP) mediated by heparan sulfate proteoglycan (HSPG) or direct HSPG-LRP uptake and direct HSPG uptake. One of the prerequisites for particles to be transported by these mechanisms is a mean diameter of less than 100-300 run. 

Figure 26-19 Endogenous lipoprotein metabolism pathway. TG, Triglyceride CE, cholesterol ester FC, free cholesterol PL, phospholipids HDL, high-density lipoproteins LDL low-density lipoproteins IDL, intermediate-density lipoproteins VLDL very low-density lipoproteins FA, fatty acid LPL, lipoprotein lipase LCAL lecithin cholesterol acyltransferase B, apolipoproteln B-tOO A, apolipoprotein A-l C, apolipoprotein C-fl , apofipoprotein E. (From RIfai N. Lipoproteins and apolipoproteins Composition, metabolism, and association with coronary heart disease. Arch Pathol Lab Med 1986 110 694-701. Copyright 1986, American Medical Association.)...

Lipoprotein Metabolism. Figure 2 Endogenous pathway of lipoprotein metabolism. 

In the endogenous pathway of lipid transport, lipids are. secreted from the liver. Tliese are triglycerides and cholesterol combined with apoprotein B-KX) and apoprotein B to form VLDL. The VLDL is acted on by lipoprotein lipase in the capillaries of adipo.se tissue to generate FFAs and an IDL. Some IDL binds to LDL receptors in the liver aitd is clciired from plasma by endocylosis. Approximately half of the circulating IDL is converted to LDL in the plasma by additional lo.ss of triglycerides. This LDL has a half-life in... 

The pathways of lipoprotein metabolism are complex. They include exogenous and endogenous pathways based on whether they carry lipids of dietary or hepatic origin (Figures 26-18 and 26-19) and other pathways such as the... 

Conversion of very-low-density lipoproteins (VLDLs) to low-density lipoproteins (LDLs), via intermediate-density lipoproteins (IDLs) (the endogenous pathway of lipid transport). Ox-LDL = Oxidized LDL. 

Fig. 1. Simplified schematic summary of the essential pathways for receptor-mediated human lipoprotein metabolism. The liver is the crossing point between the exogenous pathway (left-hand side), which deals with dietary lipids, and the endogenous pathway (right-hand side) that starts with the hepatic synthesis of VLDL. The endogenous metabolic branch starts with the production of chylomicrons (CM) in the intestine, which are converted to chylomicron remnants (CMR). Very-low-density lipoprotein particles (VLDL) are lipolyzed to LDL particles, which bind to the LDL receptor. IDL, intermediate-density lipoproteins LDL, low-density lipoproteins HDL, high-density lipoproteins LCAT, lecithinxholesterol acyltransferase CETP, cholesteryl ester transfer protein A, LDL receptor-related protein (LRPl) and W, LDL receptor. Lipolysis denotes lipoprotein lipase-catalyzed triacylglycerol lipolysis in the capillary bed.

The endogenous pathway begins in the iiver with the formation of VLDL. Simiiar to chyiomicrons, triglycerides are present in a higher concentration than either choiesteroi or choiesteroi esters however, the concentration difference between these lipids is much less than that seen in chylomicrons. The metabolism of VLDL also is similar to chylomicrons in that lipoprotein lipase reduces the triglyceride content of VLDL and increases the availability of free fatty acids to the muscle and adipose tissue. The resulting lipoprotein, IDL, either can be further metabolized to LDL or can be transported to the liver for receptor-mediated endocytosis. This latter effect involves an... 

Fig. 30.5. Endogenous and exogenous pathways for lipid transport and metabolism. FFA, free fatty acids LDLR, low-density lipoprotein receptor FC, free unesterified cholesterol LCAT, lecithin-cholesterol acyltransferase.

Goti, D., Reicher, H., Malle, E., Kostner, G.M., Panzenboeck, U., and Sattler, W., High-density lipoprotein (HDL3)-associated alpha-tocopherol is taken up by HepG2 cells via the selective uptake pathway and resecreted with endogenously synthesized apo-lipoprotein B-rich lipoprotein particles, Biochem. J. 332 (Pt 1), 57-65, 1998. 

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