1. BIOC 460
DR. TISCHLER
LECTURE 36
 LIPID TRANSPORT

2. 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

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. Figure 1 Five steps of lipid digestion and absorption
Lipids:
Triacylglycerol
Cholesterol esters
Phospholipids
Lingual Lipase
Gastric Lipase
STEP 1
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

5. Table 1. Steps of lipid digestion and absorption
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)
N/A
4. Passive absorption of lipolytic products
into intestinal epithelial cell
5. Assembly and export of chylomicrons
from intestinal cells to the lymphatics

6. Figure 2. Model of low density lipoprotein
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

7. Table 2. The major classes of lipoproteins and their relative content of triacylglycerol, cholesterol and protein
Class
Triacylglycerol
Cholesterol
Protein
Chylomicrons
>95% 3% 2%
Very Low Density Lipoprotein (VLDL)
70%
20%
10%
Low Density
55%
25%
High Density
15%
35%
50%

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

9. VLDL acquires apo CII (C) and E (E) from HDL
B100 (B) helps assemble and export nascent VLDL
VLDL interacts with LPL
Produce LDL
non-hepatic tissues
LIVER CE
C E CE B CE
C E
C E
bile acids B
LDL travels to tissues
B100 binds to receptors B
Apo E binds to receptor B
LDL into cell delivers cholesterol
HDL scavenges cholesterol
Figure 4. Endogenous pathway of lipid transport.

10. ACAT CE stored in droplets
Recycling of clathrin and receptor
Recycling of clathrin
Ligand/receptor dissociate in sorting endosome
LDL receptor
transport vesicle- lysosome fuse forming late endosome
lysosome
clathrin-
coated pit
ooo
late endosome
Golgi
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.

11. Table 3. Summary of lipoprotein functions
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

12. 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
binds liver receptor for remnants to enter cell
VLDL
B-100
assembly of VLDL
binds liver receptor for VLDL to enter cell
LDL
binds LDL receptor for LDL to enter cell
HDL A1
facilitates cholesterol efflux from cells
HDL stored, transfer to chylos/VLDL
binds liver receptor for HDL to enter cell