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LIPID TRANSPORT
DR. TISCHLER
OBJECTIVES
1. List the lipid components of the diet.
2. Describe the five steps of digestion and absorption of lipids
including the important enzymes and location where each
step occurs.
3. Describe the general structure of a lipoprotein
4. 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
OBJECTIVES
5. Discuss the function of lipoprotein lipase.
6. 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.
7. Describe how defects in the LDL receptor are associated
with familial hypercholesterolemia and atherosclerosis
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.
Figure 1 Five steps of lipid
digestion and absorption
Lipids:
Triacylglycerol
Cholesterol esters
Phospholipids
Lingual Lipase
STEP 1
Gastric Lipase
STEP 2
Pancreas releases:
Lipase (+colipase)
cholesterol esterase pancreas
phospholipase A2
STEP 3
Liver releases bile
acids to solubilize
lipid products in
mixed micelles
liver
stomach
small intestine
STEP 4
Lipids absorbed
from micelles into
epithelial cells
STEP 5
Chylomicrons form and
travel through lymphatics
Table 1. Steps of lipid digestion and absorption
Step
Location
Enzymes
1. Minor digestion
(TAGs  DAGs + FFA)
mouth and stomach
lingual/ gastric
lipase
lumen of the small
intestines
pancreatic lipase
(+colipase)
cholesterol esterase
phospholipase A2
lumen of the small
intestines
N/A
2. Major digestion (all)
TAG  MAG + 2FFA (PL)
CE  chol. + ester (CE)
PL  FA + lysoPL (PLA)
3. Formation of mixed
micelles
(uses bile salts as
biological detergent)
4. Passive absorption of into intestinal
lipolytic products
epithelial cell
N/A
5. Assembly and export
of chylomicrons
N/A
from intestinal cells
to the lymphatics
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
Table 2. The major classes of lipoproteins and their
relative content of triacylglycerol, cholesterol and protein
Class
Triacylglycerol
Cholesterol
Protein
>95%
3%
2%
Very Low Density
Lipoprotein (VLDL)
70%
20%
10%
Low Density
20%
55%
25%
High Density
15%
35%
50%
Chylomicrons
I
N
T
E
S
T
I
N
E
Lymph
system:
ApoB48
helps with
chylomicron
chylomicron interacts
with lipoprotein lipase
removing FFA
chylomicrons
acquire apo
CII (C) and E
(E) from HDL
non-hepatic tissues
CE
CE
CE CE
CE
CE CE
CE CE
chylomicron remnants
travel to liver
C
E
E EC
E C
EE E
Liver: apo E on
remnants bind receptor
Cholesterol
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
B100 (B) helps
assemble and export
nascent VLDL
VLDL acquires
apo CII (C) and E
(E) from HDL
VLDL interacts with LPL
Produce LDL
non-hepatic tissues
LIVER
CE
bile
acids
CE
CE CE CE C EC E CECE
LDL travels to tissues
B100 binds to receptors
Apo E binds to
receptor
BB
C
C
EB
E
B
B
B BB
B BB
LDL into cell delivers
cholesterol
Figure 4. Endogenous pathway of lipid transport.
HDL
scavenges
cholesterol
Recycling
Recyclingofof
clathrin
clathrinand receptor
LDL
receptor
Ligand/receptor
dissociate in
sorting endosome
transport vesiclelysosome fuse forming
late endosome
lysosome
clathrincoated pit
o
o
o
o
o
o
endocytosis
vesicle
Golgi
late endosome NPC-1
mediated free pool of
transfer
cholesterol
CEcholesterol
B100  a. acids
ACAT
CE stored
in droplets
CE CE
LDL
CE
Figure 5. Steps in the cellular uptake of cholesterol via the LDL receptor.
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 nonhepatic tissues and delivers to the liver
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