The document discusses lipoprotein metabolism, emphasizing their composition, classification, and various metabolic pathways, including chylomicrons, VLDL, LDL, and HDL. It outlines the roles of apolipoproteins and their functions in lipid transport and regulation, as well as the implications of lipoprotein levels on cardiovascular health. Additionally, it highlights the significance of HDL as 'good cholesterol' and its protective effects against heart disease.

1. Lipoprotein Metabolism
Prepared by: Mohammad Reza Abdullahi
Master of Medical Sciences in Biochemistry
Kabul University of Medical Sciences
Allied Health Faculty
Medical Laboratory Technology Department

2. Contents
• Biomedical importance
• Composition of lipoproteins
• Classification of lipoproteins
• Apolipoprotein
• Metabolism of chylomicron
• Metabolism of VLDL
• Metabolism of LDL
• Metabolism of HDL
• Lipoprotein a
• Hyperlipoproteinemia
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3. Biomedical importance
• Lipoproteins are spherical macromolecular complexes of lipids and
specific proteins (apolipoproteins).
• Transport of lipid in blood plasma
• Abnormalities of lipoprotein metabolism cause various hypo- or
hyperlipoproteinemias.
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4. Composition of lipoproteins
• Lipoproteins are composed of a neutral lipid core (containing
triacylglycerol [TAG] and cholesteryl esters) surrounded by a shell of
amphipathic apolipoproteins , phospholipid, and unesterified (free)
cholesterol
• These amphipathic compounds are oriented so that
their polar portions are exposed on the surface of
the lipoprotein, thereby rendering the particle soluble
in aqueous solution
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5. Classification of Lipoproteins
• Depending on the density (by ultra centrifugation) or
on the electrophoretic mobility, the lipoproteins in
plasma are classified into five major types
1. Chylomicrons—contains apoprotein B-48.
2. Very low density lipoproteins (VLDL) or pre-beta
lipoproteins. Main apoprotein is B-100.
3. Intermediate density lipoproteins (IDL) or broadbeta
lipoproteins
4. Low density lipoproteins (LDL) or beta-lipoproteins.
Major apoprotein in LDL is B-100.
5. High density lipoproteins (HDL) or alpha-lipoproteins.
Major apoprotein in HDL is apo-A.
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6. Con…
• Separation by Ultracentrifugation
The lipoproteins are characterized on the
basis of their density. Fat is less dense than
water; so fat floats on water. Lipoproteins
with high lipid content will have a low
density and so float on centrifugation.
• Separation by Electrophoresis
Those with higher protein content will
move faster towards the anode and those
with less proteins have minimum mobility
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7. Apolipoprotein
• The protein part of lipoprotein is called apolipoprotein (apo-Lp) or apoprotein
• Mostly synthesized in the liver
• Some apolipoproteins are integral and cannot be removed (eg, apo B), whereas
others are bound to the surface and are free to transfer to other lipoproteins, eg.
apos C and E).
• Functions:
1) They can form part of the structure of the lipoprotein, for example, apo B48 in
chylomicron and apo B100 in LDL
2) They are enzyme cofactors, for example, C-II for lipoprotein lipase, A-I for
lecithin:cholesterol acyltransferase, or enzyme inhibitors, for example, apo A-II
and apo C-III for lipoprotein lipase, apo C-I for cholesteryl ester transfer protein
3) They act as ligands for interaction with lipoprotein receptors in tissues, for
example, apo B-100 and apo E for the LDL receptor, A-I for the HDL receptor
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8. Metabolism of Chylomicron
• Chylomicrons are assembled in intestinal mucosal cells and carry dietary (exogenous) TAG,
cholesterol, fat-soluble vitamins , and cholesteryl esters to the peripheral tissues.
1) Synthesis of apolipoproteins: Apo B-48 is unique to chylomicrons
2) Assembly of chylomicron: Assembly of the apolipoproteins and lipid into chylomicrons requires
microsomal triglyceride transfer protein (MTP)which loads apo B-48 with lipid.
3) Modification of nascent chylomicron particles: nascent chylomicron receaving apo E & CII from
HDL.
4) Degradation of triacylglycerol by lipoprotein lipase: LPL which is located in capillary walls of
most tissues hydrolysis TAG to FFA and glycerol.
5) Regulation of LPL activity: in the fed state (elevated insulin levels ), LPL synthesis is increased in
adipose but decreased in muscle tissue . Fasting (decreased insulin) favors LPL synthesis in
muscle .
6) Formation of chylomicron remnants: chylomicron loses 90% of its TAG and become smaller and
denser, apo CII returned to HDL and the particle called chylomicron remnant which taken by
hepatic cells (receptors in liver recognize apo E).
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10. Metabolism of very low density
lipoproteins
• VLDLs are produced in the liver. They are composed predominantly of
endogenous TAG (approximately 60%), and their function is to carry this
lipid from the liver to the peripheral tissues.
1) Release from liver: VLDLs are secreted directly into the blood by the
liver as nascent particles containing apo B-100. They must obtain apo
C-II and apo E from circulating HDL.
2) Modification in the circulation: TAG in VLDL degraded by LPL, causing
the VLDLs to decrease in size and become denser. apo C and E, are
returned to HDL, Additionally, some TAGs are transferred from VLDL
to HDL in an exchange reaction that concomitantly transfers
cholesteryl esters from HDL to VLDL. This exchange is accomplished
by cholesteryl ester transfer protein (CETP).
3) Conversion to low density lipoprotein: With these modifications, the
VLDL is converted in the plasma to IDL, then LDL.
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12. Metabolism of low density lipoproteins
• The primary function of LDL particles is to provide cholesterol to the
peripheral tissues. They do so by binding to cell surface membrane LDL
receptors that recognize apo B-100.
• The LDL is taken up by peripheral tissues by receptor-mediated
endocytosis. LDL receptors are located in specialized regions called clathrin
coated pits. When the apo B-100 binds to the apo-B-100 receptor, the
receptor-LDL complex is internalized by endocytosis.
• The endosome vesicle thus formed fuses with lysosomes. The receptor is
recycled and returns to the cell surface. The LDL particle, along with
apoproteins and cholesterol ester are hydrolyzed by lysosomal hydrolases,
forming amino acids and free cholesterol. The free receptors can now
return to the membrane surface to bind further LDL molecules
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13. Con…
• The free cholesterol is incorporated into plasma membranes or esterified
(by ACAT) and stored within the cell. In addition, it could be used for
synthesis of steroid hormones.
• The level of intracellular cholesterol is regulated through cholesterol-
induced suppression of LDL receptor synthesis and cholesterol-induced
inhibition of cholesterol synthesis.
• The increased level of intracellular cholesterol that results from LDL uptake
activates ACAT, thereby allowing the storage of excess cholesterol within
cells. However, the effect of cholesterol-induced suppression of LDL
receptor synthesis is to decrease the rate at which LDLs and IDLs are
removed from the serum. This can lead to excess circulating levels of
cholesterol. The excess cholesterol tends to be deposited within the
arteries, leading to atherosclerosis.
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15. LDL and cardiovascular disease
• The LDL concentration in blood has positive correlation with incidence of
cardiovascular diseases.
• A fraction of cholesterol is taken up by macrophages; this is not a regulated
pathway. Increased levels of LDL or modification of LDL by glycation (as
seen in diabetes mellitus) or oxidation increases the fraction of cholesterol
taken up by macrophages.
• LDL infiltrates through arterial walls, and are taken up by macrophages or
scavenger cells. This is the starting event of atherosclerosis leading to
myocardial infarction.
• When these cells become engorged with cholesterol, foam cells are
formed, that get deposited in the sub-endothelial space triggering
formation of atheromatous plaque.
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17. Metabolism of HDL
• HDL particles are formed in blood by the addition of lipid to apo A-1, an
apolipoprotein made by the liver and intestine and secreted into blood.
[HDLs are also formed within the liver and intestine.]
• HDL functions:
• Apolipoprotein supply:: Apo CII & apo E
• Uptake of unesterified cholesterol: Nascent HDL which is disk shaped particles take
up cholesterols from peripheral tissue.
• Esterification of cholesterol: cholestereol esterify to colesterol esters by LCAT.
Incresead cholesterol esters convert discoidal nascent HDL to spherical HDL3 and
HDL2. CETP moves some of cholestryl esters to VLDL in exchange for TAG.
• Reverse cholesterol transport: HDL transfer cholestrol from peripheral tissue to liver.
HDL is taken up by hepatic scavenger receptor B1. Hepatic lipase hydrolyzes HDL
phospholipid and TAG, and cholesterol esters are released into liver cells. The
cholesterol that reaches the liver is used for synthesis of bile acids or excreted as
such in bile. Therefor, HDL is called good cholesterol.
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19. Clinical significance of HDL-C
• The level of HDL-C in serum is inversely related to the incidence of
myocardial infarction. As it is “anti-atherogenic” or “protective” in
nature, HDL is known as “good cholesterol” in common parlance.
• HDL-C level below 35 mg/dL increases the risk, while level above 60
mg/dL protects the person from coronary artery diseases.
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20. Lipoprotein a or Lp (a)
• Lp (a) is structurally releated to LDL because both lipoproteins
possess one molecule of apo B-100 per particle with similar lipid
compositions. Unlike LDL, Lp(a) also contains a carbohydrate-rich
protein [apo(a)], which is covalently bound to the apo B-100 through
a disulfide linkage.
• Apo(a) is structurally homologous to plasminogen, the precursor of a
blood protease whose target is fibrin, the main protein component of
blood clots.
• It is hypothesized that elevated Lp(a) slows the breakdown of blood
clots that trigger heart attacks because it competes with plasminogen
for binding to fibrin.
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21. Hyperlipoproteinemia
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22. Reference
• Lippincott’s illustrated Reviews Biochemistry/[edited by] Denise R.
Ferrier- 6th edition
• Textbook of Biochemistry for Medical Students/[edited by] DM
Vasudevan, Sreekumari S, Kannan Vaidyanathan- 7th ed.
• Clinical chemistry : principles, techniques, and correlations/[edited by]
Michael L. Bishop, Edward P. Fody, Larry E. Schoeff.—8th ed.
• TIETZ FUNDAMENTALS OF CLINICAL CHEMISTRY/[edited by] Carl A.
Burtis, David E. Bruns- 7th edition
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23. Thanks
For your
attention
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