DR. TISCHLER

1. LIPID TRANSPORT DR. TISCHLER

2. OBJECTIVES • List the lipid components of the diet. • Describe the five steps of digestion and absorption of lipids including the important enzymes and location where each step occurs. • Describe the general structure of a lipoprotein • Name the 4 main classes of lipoproteins and • a) indicate whether each is in the exogenous or the endogenous system. • b) identify the major lipid component in each. • c) describe their lipid-transport functions. • d) list their key apoproteins and the functions of these apoproteins

3. OBJECTIVES • Discuss the function of lipoprotein lipase. • Outline the steps in the processing of: • a) chylomicrons from their synthesis in the intestinal cell to the delivery of cholesterol in chylomicron remnants to the liver. • b) VLDL from its synthesis in the liver to the delivery of cholesterol to cells via the low-density-lipoprotein (LDL)receptor including the cellular uptake and processing of cholesterol via LDL. • Describe how defects in the LDL receptor are associated with familial hypercholesterolemia and atherosclerosis

4. Fat (lipid) makes up 37% of the calories in the American diet • Fat is energy rich and provides 9 kcal/gm • Dietary lipids are 90% triacylglycerols, but also include cholesterol esters, phospholipids, essential unsaturated fatty acids and fat soluble vitamins • Normally essentially all (98%) of the fat consumed is absorbed, and most is transported to adipose for storage.

5. Lingual Lipase STEP 1 Gastric Lipase Figure 1 Five steps of lipid digestion and absorption Lipids: Triacylglycerol Cholesterol esters Phospholipids stomach STEP 2 Pancreas releases: Lipase (+colipase) cholesterol esterase phospholipase A2 small intestine pancreas STEP 4 Lipids absorbed from micelles into epithelial cells STEP 3 Liver releases bile acids to solubilize lipid products in mixed micelles liver STEP 5 Chylomicrons form and travel through lymphatics

6. Table 1. Steps of lipid digestion and absorption

7. Figure 2. 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

8. Table 2. The major classes of lipoproteins and their relative content of triacylglycerol, cholesterol and protein

9. chylomicrons acquire apo CII (C) and E (E) from HDL CE CE CE CE CE E CE CE E CE CE C E C chylomicron remnants travel to liver E C E E E Liver: apo E on remnants bind receptor Cholesterol deposited in liver chylomicron interacts with lipoprotein lipase removing FFA Lymph system: INTEST INE non-hepatic tissues ApoB48 helps with chylomicron LIVER Figure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty acids to tissues and remnants take cholesterol to the liver

10. VLDL acquires apo CII (C) and E (E) from HDL B100 (B) helps assemble and export nascent VLDL CE CE CE CE CE CE C E C E CE C E C E bile acids LDL travels to tissues B100 binds to receptors Apo E binds to receptor B B B B B B B B B B B VLDL interacts with LPL Produce LDL non-hepatic tissues LIVER LDL into cell delivers cholesterol HDL scavenges cholesterol Figure4. Endogenous pathway of lipid transport.

11. LDL receptor Recycling of clathrin and receptor Recycling of clathrin Ligand/receptor dissociate in sorting endosome transport vesicle- lysosome fuse forming late endosome lysosome clathrin- coated pit ooo Golgi late endosome NPC-1 mediated transfer ooo free pool of cholesterol ACAT CEcholesterol B100  a. acids endocytosis CE stored in droplets vesicle CE CE LDL CE Figure 5. Steps in the cellular uptake of cholesterol via the LDL receptor.

12. Table 3. Summary of lipoprotein functions

13. Table 4. Summary of apoproteins and their characteristics