Lefevre05.ppt - Lipoprotein Assembly and Metabolism Lecture...

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Lipoprotein Assembly and Metabolism
Lecture Outline What are lipoproteins? What do they do Basic structure of lipoproteins Lipoprotein metabolism Cholesterol homeostasis Development of atherosclerosis Role of lipoproteins in atherosclerosis Role of diet in atherosclerosis prevention
Lipoprotein Overview
What are lipoproteins? Lipoproteins are protein-lipid complexes .
The Players – Lipids Triacylglycerol Phospholipids Cholesterol Cholesteryl esters
What are lipoproteins? Hydrophobic lipids (TG, CE) in core; Hydrophilic lipids (UC, PL) on surface
The Players – Lipids Triacylglycerol Phospholipids Cholesterol Cholesteryl esters
The Players - Apolipoproteins Apo AI (liver, small intestine) Structural; activator of lecithin:cholesterol acyltransferase (LCAT) Apo AII (liver) Structural; inhibitor of hepatic lipase; component of ligand for HDL binding Apo A-IV (small intestine) Activator of LCAT; modulator of lipoprotein lipase (LPL) Apo A-V (liver) Direct functional role is unknown; regulates TG levels.
Apolipoproteins Apo B-100 (liver) Structural; synthesis of VLDL; ligand for LDL- receptor Apo B-48 (small intestine) Structural; synthesis of chylomicrons; derived from apo B-100 mRNA following specific mRNA editing Apo E (liver, macrophages, brain) Ligand for apoE receptor; mobilization of cellular cholesterol
Apolipoproteins Apo C-I (liver) Activator of LCAT, inhibitor of hepatic TGRL uptake Apo C-II (liver) Activator of LPL, inhibitor of hepatic TGRL uptake Apo C-III (liver) Inhibitor of LPL, inhibitor of hepatic TGRL uptake
Amphipathic Helices Lipoprotein Surface
What do lipoproteins do? Serve to transport lipid-soluble compounds between tissues Substrates for energy metabolism (TG) Essential components for cells (PL, UC) Precursors for hormones Precursors for eicosanoids Lipid soluble vitamins Precursors for bile acids
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 their catabolic remnants remnants > 30 nm > 30 nm 20–22 nm 20–22 nm 9–15 nm 9–15 nm D<1.006 g/ml D<1.006 g/ml D=1.019-1.063g/ml D=1.019-1.063g/ml D=1.063-1.21 g/ml D=1.063-1.21 g/ml Lipids Online
Lipoprotein Metabolism Exogenous/chylomicron pathway (dietary fat) Endogenous pathway (lipids synthesized by the liver) HDL metabolism (apolipoprotein transfer, cholesteryl ester transfer, reverse cholesterol transport
Lipoprotein Metabolism Exogenous/chylomicron pathway (dietary fat) Endogenous pathway (lipids synthesized by the liver) HDL metabolism (apolipoprotein transfer, cholesteryl ester transfer, reverse cholesterol transport
Surface Monolayer Surface Monolayer Phospholipids (5%) Phospholipids (5%) Free Cholesterol (1%) Free Cholesterol (1%) Protein (1%) Protein (1%) Hydrophobic Core Hydrophobic Core Triglyceride (93%) Triglyceride (93%) Cholesteryl Esters (1%) Cholesteryl Esters (1%) TG Rich: Chylomicrons Cholesterol and Atherosclerosis, Grundy)
Chylomicron Metabolism Cholesterol and Atherosclerosis, Grundy)

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