BIOC 460

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BIOC 460 DR. TISCHLER LECTURE 36
 LIPID TRANSPORT
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OBJECTIVES

• Common 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

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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

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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
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Table 1. Steps of lipid digestion and absorption
Step Location Enzymes
1. Minor digestion (TAGs ? DAGs FFA) mouth and stomach lingual/ gastric lipase
2. Major digestion (all) TAG ? MAG 2FFA (PL) CE ? chol. ester (CE) PL ? FA lysoPL (PLA) lumen of the small intestines pancreatic lipase (colipase) cholesterol esterase phospholipase A2
3. Formation of mixed micelles (uses bile salts as biological detergent) lumen of the small intestines N/A
4. Passive absorption of lipolytic products into intestinal epithelial cell N/A
5. Assembly and export of chylomicrons from intestinal cells to the lymphatics N/A
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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
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Table 2. The major classes of lipoproteins and
their relative content of triacylglycerol,
cholesterol and protein
Class Triacylglycerol Cholesterol Protein
Chylomicrons gt95 3 2
Very Low Density Lipoprotein (VLDL) 70 20 10
Low Density 20 55 25
High Density 15 35 50
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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
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VLDL interacts with LPL Produce LDL
non-hepatic tissues
LIVER
LDL into cell delivers cholesterol
HDL scavenges cholesterol
Figure 4. Endogenous pathway of lipid transport.
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Recycling of clathrin
Recycling of clathrin and receptor
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.
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Table 3. Summary of lipoprotein functions
Lipoprotein Function
Chylomicron deliver fatty acids as part of triacylglycerol, from dietary fat to muscle, adipose
Chylomicron remnants deliver dietary cholesterol to the liver
VLDL deliver fatty acids, attached to triacylglycerol, derived from liver synthesis to non-hepatic tissues (e.g., muscle, adipose)
LDL from VLDL delivers cholesterol, derived from liver synthesis to various tissues
HDL collects (scavenges) cholesterol from non-hepatic tissues and delivers to the liver
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Table 4. Summary of apoproteins and their
characteristics
Lipoprotein Apoprotein Function
Chylomicron B-48 CII E chylomicron formation activates LPL transferred to remnants
Chylomicron remnants E binds liver receptor for remnants to enter cell
VLDL B-100 CII E assembly of VLDL activates LPL binds liver receptor for VLDL to enter cell
LDL B-100 binds LDL receptor for LDL to enter cell
HDL A1 CII E facilitates cholesterol efflux from cells HDL stored, transfer to chylos/VLDL binds liver receptor for HDL to enter cell