3. Fat from the diet and lipids synthesized by the
liver and adipose tissue must be transported
between the various tissues and organs for
utilization and storage.
Lipids are insoluble in water
3Joseph Dut Buol
4. The Plasma Lipoproteins
Lipids Are Transported in the Plasma as
Lipoproteins.
Lipoproteins are spherical macromolecular
complexes of lipids and specific proteins
(apolipoproteins or apoproteins)
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5. Surface: polar
Core (centre): non polar
Non-polar lipid core consists of TAG and
cholesteryl ester.
Surface: of amphipathic phospholipid and free
cholesterol & proteins.
The protein part is known as an
apolipoprotein or apoprotein
5Joseph Dut Buol
7. Major Groups of Plasma Lipoproteins
The density of a lipoprotein decreases as the proportion of lipid to protein
increases.
Four major groups of lipoproteins have been identified that are important
physiologically and in clinical diagnosis.
These are:
1. Chylomicrons, derived from intestinal absorption of TAG and other lipids
2. Very low density lipoproteins (VLDL) derived from the liver for the
export of TAG
3. Low-density lipoproteins (LDL) representing a final stage in the
catabolism of VLDL
4. High-density lipoproteins (HDL) involved in cholesterol transport and
also in VLDL and chylomicron metabolism.
TAG is the predominant lipid in chylomicrons and VLDL, whereas
cholesterol is predominant in LDL and phospholipid are the predominant
lipids in HDL.
7Joseph Dut Buol
8. The main apolipoprotein of HDL (α-
lipoprotein) designated A
The main apolipoprotein of LDL (β-
lipoprotein) is apolipoprotein B (B-100) and is
found also in VLDL.
Chylomicrons apoB (B-48)
B-48: synthesis(intestine)
B-100 synthesis(liver)
Apolipoproteins
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9. Apo C-I, C-II, and C-III are smaller polypeptides
Freely transferable between different
lipoproteins.
Apo E is found in VLDL, HDL, chylomicrons,
and chylomicron remnants;
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10. Funtions of Apolipoproteins:
1. form part of the structure of the lipoprotein
2. enzyme cofactors, eg, C-II for lipoprotein
lipase
3. ligands for interaction with lipoprotein
receptors in tissues, eg, apo B-100 and apo E
for the LDL receptor.
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11. Four Major Lipid Classes Are Present in
Lipoproteins
Plasma lipids consist of
1. Triacylglycerols (16%)
2. Phospholipids (30%)
3. Cholesterol (14%)
4. Cholesteryl esters (36%) and
5. Free fatty acids (FFA) (4%)
11Joseph Dut Buol
12. Major Groups of Plasma Lipoproteins
The density of a lipoprotein decreases as the proportion of lipid to protein
increases.
Four major groups of lipoproteins have been identified that are important
physiologically and in clinical diagnosis.
These are:
1. Chylomicrons, derived from intestinal absorption of TAG and other lipids
2. Very low density lipoproteins (VLDL) derived from the liver for the
export of TAG
3. Low-density lipoproteins (LDL) representing a final stage in the
catabolism of VLDL
4. High-density lipoproteins (HDL) involved in cholesterol transport and
also in VLDL and chylomicron metabolism.
TAG is the predominant lipid in chylomicrons and VLDL, whereas
cholesterol is predominant in LDL and phospholipid are the predominant
lipids in HDL.
12Joseph Dut Buol
13. The major components of lipoproteins are triacylglycerols,
cholesterol, cholesterol esters, phospholipids, and proteins. The
protein components (called apoproteins) are designated A, B, C,
and E.
1. Chylomicrons are the least dense of the blood lipoproteins
because they have the most TAG and the least protein.
2. Very-low-density lipoprotein (VLDL) is more dense than
chylomicrons but still has a high content of TAG.
3. Intermediate-density lipoprotein (IDL), which is derived from
VLDL, is denser than VLDL and has less than half the amount of
TAG of VLDL.
4. Low density lipoprotein (LDL) has less TAG than IDL and more
protein and, therefore, is denser than the IDL from which it is
derived. LDL has the highest content of cholesterol and its esters.
5. High-density lipoprotein (HDL) is the densest lipoprotein. It has
the lowest TAG content and the highest protein content of all the
lipoprotein particles.
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15. Metabolism of Chylomicrons
Chylomicrons are synthesized in intestinal epithelial cells. Their
TAGs are derived from dietary lipid, and their major apoprotein
(apo) is apo B-48.
Chylomicrons travel through the lymph into the blood. (Step 1) Apo
C-II, the activator of lipoprotein lipase, and apo E are transferred to
nascent chylomicrons from HDL, and mature chylomicrons are
formed. (Step 2)
In peripheral tissues, particularly adipose and muscle, the TAGs are
digested by lipoprotein lipase. As the chylomicron loses TAG, a
chylomicron remnant is formed.
The chylomicron remnants interact with receptors on liver cells and
are taken up by endocytosis.
The contents are degraded by lysosomal enzymes, and the
products (amino acids, fatty acids, glycerol, cholesterol, and
phosphate) are released into the cytosol and reused.
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16. Metabolism of VLDL
VLDL is synthesized in the liver, particularly after a
high-carbohydrate meal. It is formed from TAGs that
are packaged with cholesterol, apoproteins
(particularly apo B-100), and phospholipids, and it is
released into the blood.(Step 3)
In peripheral tissues, particularly adipose and muscle,
VLDL TAGs are digested by lipoprotein lipase, and VLDL
is converted to IDL.
IDL returns to the liver, is taken up by endocytosis, and
is degraded by lysosomal enzymes. (Step 4)
IDL can also be further degraded, forming LDL. (Step 5)
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17. LDL
LDL reacts with receptors on various cells, is taken up by
endocytosis, and is digested by lysosomal enzymes. (Step 6)
Cholesterol, released from cholesterol esters by a lysosomal
esterase, can be used for the synthesis of cell membranes or for
the synthesis of bile salts in the liver or steroid hormones in
endocrine tissue.
Cholesterol inhibits HMG-CoA reductase (a key enzyme in
cholesterol biosynthesis) and, thus, decreases the rate of
cholesterol synthesis by the cell.
Cholesterol inhibits synthesis of LDL receptors (downregulation)
and, thus, reduces the amount of cholesterol taken up by cells.
Cholesterol activates acyl:cholesterol acyltransferase (ACAT), which
converts cholesterol to cholesterol esters for storage in cells.
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20. Metabolism of HDL
HDL is synthesized by the liver and released into
the blood as small, disk-shaped particles.
The major protein of HDL is apo A
Apo C-II, which is transferred by HDL to
chylomicrons and VLDL, serves as an activator of
lipoprotein lipase.
Apo E is also transferred and serves as a
recognition factor for cell surface receptors.
Apo C-II and apo E are transferred back to HDL
after digestion of TAGs of chylomicrons and VLDL.
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21. Tangier disease is a disease of cholesterol transport. The first case was
identified in a patient who lived on the island of Tangier and who had
characteristic orange-colored tonsils, a very low HDL level, and an
enlarged liver and spleen. Because of a mutation in a transport protein,
cholesterol cannot properly exit the cell to bind to apo A (forming HDL).
This results in a very low HDL level.
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22. Cholesterol, obtained by HDL from cell membranes or
from other lipoproteins, is converted to cholesterol
esters within the HDL particle by the
lecithin:cholesterol acyltransferase (LCAT)[known as
phosphatidylcholine:cholesterol acyltransferase (PCAT)]
reaction, which is activated by apo A-I.
a. A fatty acid from position 2 of lecithin
(phosphatidylcholine), a component of HDL, forms an
ester with the 3-hydroxyl group of cholesterol,
producing lysolecithin and a cholesterol ester.
b. As cholesterol esters accumulate in the core of the
lipoprotein, HDL particles become spheroids.
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23. HDL transfers cholesterol esters to other lipoproteins
in exchange for various lipids. Cholesterol ester
transfer protein (CETP) mediates this exchange. VLDL
and other lipoproteins carry the cholesterol esters back
to the liver.
HDL particles and other lipoproteins are taken up by
the liver by endocytosis and hydrolyzed by lysosomal
enzymes.
Cholesterol, released from cholesterol esters, can be
packaged by the liver in VLDL and released into the
blood or converted to bile salts and secreted into the
bile.
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24. LCAT deficiency results in an inability to convert cholesterol associated with
HDL to cholesterol esters. Ordinarily, these cholesterol esters would be transferred
to other lipoproteins, which would then be taken up by receptors in the liver.
Therefore, by inducing esterification of cholesterol, LCAT is important for the
continued removal of cholesterol from the periphery. Clinical manifestations
include defects in the kidneys, red blood cells, and the cornea of the eyes.
24Joseph Dut Buol
26. Hyperlipidemias
Disease Description Etiology of Lipid
Disorder
Biochemical Finding
Type I Hyperlipoproteinemia (rare
genetic disorders)
Lipoprotein lipase
deficiency or apo C-II
deficiency
Chylomicrons high
Type IIa Familial hypercholesterolemia
(common autosomal dominant
inheritance)
LDL receptor deficiency Elevated LDL only
Type IIb Familial combined
hyperlipoproteinemia (common
autosomal dominant inheritance
Decreased LDL receptor
and increased Apo B
LDL and VLDL high and
triglycerides < 1000
mg/dL
Type III Familial dysbetalipoproteinemia
(rare)
Apo E defect Increased IDL (a VLDL
remnant)
Type IV Familial hyperlipemia (common) VLDL overproduction along
with decreased clearance
Increased VLDLs
Type V Hypertriglyceridemia with
Chylomicronemia (uncommon)
Increased VLDL production
and decreased lipoprotein
lipase production
Chylomicrons and VLDL
elevated
26Joseph Dut Buol
28. ONE
Which of the following apoproteins is an
activator of lipoprotein lipase?
(A) Apo A
(B) Apo B
(C) Apo C-II
(D) Apo D
(E) Apo E
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29. TWO
The major carriers of triacylglycerols are
which of the following?
(A) Chylomicrons and VLDL
(B) IDL and LDL
(C) VLDL and LDL
(D) HDL and LDL
(E) Chylomicrons and LDL
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30. THREE
An 8-year-old boy presents with orange-colored tonsils,
a very low HDL level, and an enlarged liver and spleen
and is diagnosed with Tangier disease. Which of the
following statements best describes HDL?
(A) It is produced in skeletal muscle.
(B) It scavenges cholesterol from cell membranes.
(C) Its major protein is apo E.
(D) It is formed when VLDL is digested by lipoprotein
lipase.
(E) It activates ACAT.
30Joseph Dut Buol
31. FOUR
A 25-year-old woman presents with a low red blood
cell count, corneal opacities, and kidney insufficiency.
She is diagnosed with LCAT deficiency. LCAT is involved
in which of the following processes?
(A) Converting cholesterol to cholesterol esters
(B) The transfer of cholesterol esters from HDL to other
lipoproteins
(C) Endocytosis of HDL particles into hepatocytes
(D) Hydrolysis of HDL
(E) Decreased uptake of cholesterol by hepatocytes
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32. FIVE
A 55-year-old woman presents with crushing substernal
chest pain and shortness of breath. A coronary artery is
occluded owing to an atherosclerotic plaque, and a high
myocardial infarct is diagnosed. High serum HDL levels are
protective against the development of atherosclerosis
because HDL does which of the following?
(A) Inhibits cholesterol production by the liver
(B) Inhibits HMG-CoA reductase
(C) Increases VLDL production
(D) Increases LDL production
(E) Brings cholesterol esters back to the liver
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33. SIX
A 30-year-old man presents with weakness in his right upper and
lower extremities. He is diagnosed with an acute middle cerebral
artery stroke secondary to atherosclerosis. Genetic studies show
that he has familial hypercholesterolemia, type II, a disorder caused
by a deficiency of LDL receptors. Which of the following statements
best describes patients with type II familial hypercholesterolemia?
(A) After LDL binds to the LDL receptor, the LDL is degraded
extracellularly.
(B) The number of LDL receptors on the surface of hepatocytes
increases.
(C) Cholesterol synthesis by hepatocytes increases.
(D) Excessive cholesterol is released by LDL.
(E) The cholesterol level in the serum decreases.
33Joseph Dut Buol
34. SEVEN
A young girl with a history of severe
abdominal pain was taken to her local hospital
at 5 a.m. in severe distress. Blood was drawn,
and the plasma appeared milky, with the
triacylglycerol level in excess of 2,000 mg/dl
(normal = 4–150 mg/dl). The patient was
placed on a diet severely limited in fat, but
supplemented with medium-chain fatty acids.
34Joseph Dut Buol
35. A
Which of the following lipoprotein particles are
most likely responsible for the appearance of the
patient’s plasma?
A. Chylomicrons.
B. Very-low-density lipoproteins.
C. Intermediate-density lipoproteins.
D. Low-density-lipoproteins.
E. High-density-lipoproteins.
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36. B
Medium-chain fatty acids are given because they:
A. Are more calorically dense than long-chain fatty acids.
B. Enter directly into the portal blood, and can be
metabolized by the liver.
C. Are activators of lipoprotein lipase.
D. Are more efficiently packed into serum lipoproteins.
E. Can be converted into a variety of gluconeogenic
precursors.
F. Stimulates VLDL production by the liver.
36Joseph Dut Buol