BIOC 460

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BIOC 460 DR. TISCHLER LECTURE 30
 LIPID TRANSPORT
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OBJECTIVES
1. Describe the five steps of digestion and
absorption of lipids including the important
enzymes and location where each step
occurs. 2. Describe the general structure of a
lipoprotein 3. Name the 4 main classes of
lipoproteins and the major lipid component(s) in
each and apoproteins of each including the
function of the apoprotein. 4. Describe the
lipid-transport function of each lipoprotein. 5.
Discuss the function of lipoprotein lipase.
6. Compare and contrast the processing of
chylomicrons and VLDL. 7. Describe how
defects in the LDL receptor are associated with
familial hypercholesterolemia and
atherosclerosis.
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PHYSIOLOGICAL PREMISE Atherosclerosis is a
major cause of death in this country. Excess
cholesterol in the blood accumulates on the walls
of blood vessels which provide oxygen to the
heart. This accumulation causes the formation of
plaques. As the plaque increases in size, it
occludes the blood vessel reducing oxygen
delivery to the affected part of the heart.
Eventually no oxygen is delivered to the cells
making them ischemic. The ischemia causes cells
to die resulting potentially in a myocardial
infarction. In bypass surgery, blood vessels,
obtained from extremities, are attached to
"bypass" the area of occluded blood vessel.
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FAT FACTS

• fat (lipid) makes up 37 of the calories in the
  American diet
• energy rich and provides 9 kcal/gm
• dietary lipids 90 triacylglycerols (TAGs) also
  include cholesterol esters, phospholipids,
  essential unsaturated fatty acids fat-soluble
  vitamins
• most dietary fat transported to adipose for
  storage
• dietary TAGs hydrolyzed in the intestine by
  pancreatic lipases then reassembled in the
  intestinal cells
• dietary fats transported to tissues as TAG or
  cholesterol via chylomicrons
• at peripheral tissues (e.g., adipose or
  muscle), FA removed from the TAG by a
  lipoprotein lipase in the capillary walls
  released fatty acids diffuse into the cell

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saturated fatty acid CH3-(CH2)n-COOH unsaturat
ed fatty acid CH3-CHCH-(CH2)n-COOH polyunsatu
rated fatty acid CH3-CHCH-CH2-CHCH-(CH2)n-COOH
?
CH2----OOC-R1 CH2OH
HOOC-R1 ?
R2-COO----CH CHOH
HOOC-R2 ?

CH2----OOC-R3 CH2OH
HOOC-R3
Lipolysis
Figure 1. General structures of fatty acids and
triacylglycerol. Lipolysis of stored
triacylglycerol by lipases produces fatty acids
plus glycerol.
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Figure 2 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
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Figure 3. 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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100
80
60
Composition
40
20
0
Chylo- microns
VLDL
LDL
HDL
Lipoprotein Type
Figure 4. The major classes of lipoproteins and
their relative content of triacylglycerol (T),
cholesterol (C) and protein (P).
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chylomicron interacts with lipoprotein lipase
removing FFA
Lymph system
INTEST INE
non-hepatic tissues
ApoB48 helps with chylomicron
LIVER
Figure 5. Exogenous pathway of lipid transport.
Chylomicrons carry dietary fatty acids to tissues
and remnants take cholesterol to the liver
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CHILD WHO CANNOT ABSORB FAT BECAUSE CHYLMICRON
FORMATION IS DEFECTIVE Patient slide to be shown
in class
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Medical Scenario 59 year old male entered the
hospital suffering from chronic gnawing,
epigastric pain. The mild symptoms had become
worse in the last year, with bloating, flatulence
and loose bowel movements daily. As a boy he had
been healthy living on a diet relatively low in
fat. At 18 he became a sailor the diet on board
ship was higher in fat. At 24, he had a
perforated duodenal ulcer, which was treated
surgically. At the time of the surgery, his
blood serum was described as lipemic, with a
serum triglyceride of 1100 mg/100 ml (nllt165),
but serum cholesterol of 214 mg/100 ml
(nl150-220). Physical examination showed a
pale and wasted man. His stool contained 22.6 g
of fat per day on a diet containing 100 g of fat.
Because of a sudden fall in the patients
hemoglobin, he received a transfusion of packed
red blood cells. The hemoglobin rose to normal
and also had a remarkable effect on the plasma
triglycerides. The levels that had previously
been 1750 mg/100 ml, fell to just 196 mg/100 ml
two days after the transfusion. However over the
next 2 weeks, the triglycerides rose once again
to 1750mg/100 ml. This patient has a defect of
his apo CII. The transfusons temporarily provided
him with normal apo CII that influenced his
plasma lipoprotein levels causing the patients
triglyceride-rich lipoproteins to decrease. After
two weeks the normal apo CII was replaced with
his defective form and the hypertriglyceridemia
returned.
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VLDL interacts with LPL Produce LDL
non-hepatic tissues
LIVER
LDL into cell delivers cholesterol
HDL scavenges cholesterol
Figure 6. 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 7. Steps in the cellular uptake of
cholesterol via the LDL receptor. NPC-1
Niemann-Pick C protein moves cholesterol ACAT
(acyl CoAcholesterol acyltransferase)
esterifies cholesterol for storage.
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Planar and tuberous xanthomas, plus joint
cholesterol build-up in a patient with familial
hypercholesterolemia Slide to be shown in class
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Normal coronary artery with no atherosclerosis
and a widely patent lumen that can carry as much
blood as the myocardium requires
Coronary artery with a narrowed lumen from
atherosclerosis
SLIDES TO BE SHOWN IN CLASS
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Table 2. Summary of lipoprotein functions
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Table 3. Summary of apoproteins and their
characteristics