BCHS-4361-09-LDL-REC_39434

BCHS-4361-09-LDL-REC_39434 - LOW DENSITY LIPOPROTEIN(LDL...

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LOW DENSITY LIPOPROTEIN (LDL) RECEPTORS AND FAMILIAL HYPERCHOLESTEROLEMIA (FH) FH is a genetic disorder, which arises because of a defect in LDL receptors. We will first consider the metabolism of LDL and its relationship to other plasma lipoproteins. Lipoprotein Composition and Structure: Plasma lipids consist of triacylglycerols (TG), cholesterol (CH), phospholipids (PL), cholesterol esters (CE) and free fatty acid (FFA). FFA upon release from adipose tissue are transported in bloodstream bound to albumen. All other lipids are transported bound to proteins; these complexes are the plasma lipoproteins.
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I. PLASMA LIPOPROTEINS They are spherical particles which are constructed so their core contains hydrophobic lipid (TG and CE) and the surface coat consists of more polar lipids (CH and PL) and protein. The original basis for distinguishing among lipoproteins was by the differences in density, which is a function of the amount of core lipid they possess. The major classes of lipoproteins in order of increasing density are: – Chylomicrons Very low density lipoproteins (VLDL) Low density lipoprotein (LDL) High density lipoprotein (HDL) (In addition ,there are small amounts of intermediate density lipoprotein (IDL), which has a density between VLDL and LDL. “Common knowledge”: HDL: “good cholesterol; LDL: “bad cholesterol.
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Figure 1. Model of low density lipoprotein. Other lipoproteins have a similar structure differing in the core content of lipid and the type of apoproteins on the surface of the molecule
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0% 20% 40% 60% 80% 100% Chylo- microns VLDL LDL HDL Lipoprotein Type Composition C P T C P T T P C C P T Figure 2. The major classes of lipoproteins and their relative content of triacylglycerol ( T ), cholesterol ( C ) and protein ( P ).
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Lipoprotein classes: supplies apo CII, E to chylomicrons and VLDL; mediates reverse cholesterol transport 1:1 cholesterol ester A1, CII, E ("ACE") liver HDL CE to liver (70%) and peripheral cells (30%) 1:3 cholesterol ester B100 blood LDL Synthesized: FFA adipose/muscle CE LDL 1:9 triacylglycerol (CE) B100, CII*, E* liver VLDL Dietary: FFA Adipose/muscle CE Liver via remnants 1:49 triacylglycerol (CE) B48, CII*, E* gut Chylo- microns Function Protein:Lipid/ Major (minor) Lipid Transported Apo Proteins in Mature Source Lipo- protein
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Lipoprotein Classes Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000; 149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994. HDL HDL LDL LDL Chylomicrons Chylomicrons, VLDL, and VLDL, and their catabolic remnants remnants > 30 nm > 30 nm 20 20– 22 nm 22 nm 9– 15 nm 15 nm D<1.006 g/ml D=1.019-1.063g/ml D=1.063-1.21 g/ml Lipids Online
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II. PLASMA LIPOPROTEINS: PROTEIN COMPONENTS Apolipoproteins A-E are distributed among the various plasma llipoproteins and exert a variety of functions.
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