for educational purpose

1. LIPOPROTEINS- TRANSPORT AND
METABOLISM
SUBMITTED BY:-NAIR ANAGA MADANMOHAN
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2. Products of fat digestion:-
1. Glycerol
2. Free fatty acids
3. Monoacylglycerols
4. Diacylglycerol
1. During absorption through intestinal mucosal cells, much resynthesis of triacylgycerols occurs from the hydrolysis
products.
2. This occurs mainly in the endoplasmic reticulum and golgi apparatus of mucosal cells
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3. Triglycerols are derived from three primary sources:-
1) The diet
2) De-novo biosynthesis in the liver
3) Storage deposits in the adipocytes
1. The insolubility of lipids during digestion is met with action of bile salts on them, while the problem of
transport through the blood and lymph is dealt with by complexing of lipids with proteins to form soluble
aggregates called lipoproteins.
2. Triacylglycerols emerge into lymph system complexed with proteins to form lipoproteins called
chylomicrons.
3. Apolipoproteins (“apo” means “detached”or “separate,” designating the protein in its lipid-free
4. form) combine with lipids to form several classes of lipoprotein particles, spherical aggregates with
hydrophobic lipids at the core and hydrophilic protein side chains and lipid head groups at the surface.
5. Chylomicron- an oil droplet coated with more polar lipids and a skin of protein which helps disperse and
partially solubilize the fat for transport to tissues.
6. It is also the transport vessel for dietary cholesterol.
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6. Lipoproteins
1. Chylomicrons constitute just one class of lipoproteins present in the bloodstream.
2. Distinct families of lipoproteins are present and as classified in terms of their density as determined by
centrifugation.
3. They have a characteristic apoprotein and distinct lipid compositions.
4. A total of nine major apolipoproteins are found in human plasma
5. As lipids are much lower in terms of density than proteins the lipid content of lipoprotein class is inversely related
to its density.
6. The higher the lipid abundance the lower the density.
The standard lipoprotein class includes, in increasing order of density:-
 Chylomicrons
 Very low density lipoproteins
 Intermediate density lipoproteins
 Low density lipoproteins
 High density lipoprotein
They all share common structural features.
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1. Chylomicrons ; Formed in the mucosal cells of the small intestine .
2. Largest of lipoprotein & least dense.
3. Contains high portion of triacylglycerols.
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2. Very-low-density lipoprotein (VLDL) ; Formed in the liver.
Transport triacylglycerol , phospholipids, and cholesterol to the tissues for storage or to the muscles for energy.
90% lipid ,10%protein
3. Low-density lipoprotein (LDL) ; Synthesized from IDL.
It transport cholesterol to tissues to be used for the synthesis of cell membranes, steroid hormones, and bile salts .
78% lipid, 58% cholesterol & CE
4.High-density lipoprotein (HDL) ; It remove excess cholesterol from the tissues and carry it to the liver where it is
converted to bile salts and eliminated . 52% protein, 48% lipid, 35% C & CE
5.Very high density lipoprotein (VHDL)
( when level of LDL exceeds the amount cholesterol needed by the tissues, the LDLs deposit cholesterol in the arteries
and/or myocardial infarctions (heart stacks). ie why it is called as “bad” cholesterol.
When HDL levels are high, cholesterol that is not needed by the tissues is carried to the liver for elimination rather
than deposited in the arteries, which gives the HDLs the name of “good”cholesterol.)

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9. 1. Some apolipoproteins have specific function than being mere passive carriers of lipids from one tissue to
other.
2. Apo c-II is an activator of triacylglycerol hydrolysis by lipoprotein lipase.
3. Other lipoproteins target specific lipoproteins to targeted cells by being recognized by receptors in the
plasma membranes of the cells.
4. Together the apolipoproteins help maintain in emulsified form some 500 mg of total lipid per 10 ml of human
blood in the post absorptive state after contents of a meal are digested and absorped.
5. hence their two main functions include:-
a)Target lipoprotein to specific tissue.
b)activating enzyme that act on lipoprotein.
FUNCTIONS OF APOLIPOPROTEINS
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10. Transport of lipoproteins
1. Dietary fat is to be mainly transported from intestinal to peripheral tissues, notably
heart, muscle, and adipose tissues.
2. The triacylglycerols in the lipoproteins are hydrolysed into glycerol and fatty
acids at the inner surfaces of capillaries in the peripheral tissues.
3. This hydrolysis involves activation of extracellular enzymes lipoprotein lipase by
apoprotein c-II.
4. Some of the released free fatty acids are absorbed by the nearby cells while the still
insoluble ones are complexed with the serum albumin for transport to more distant
cells.
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11. Fate after absorption of fatty acids derived by action of lipoprotein
lipase:-
1. Storage
2. Catabolized to generate energy
3. Resynthesize triacylgycerol from adipose tissues
4. Returned to liver for synthesis of glucose
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12. CHYLOMICRONS
1. synthesized in the ER of epithelial cells that line the small intestine.
2. move from the intestinal lacteals to the lymphatic system and finally into the thoracic duct and enter the
bloodstream via the left subclavian vein.
3. Looks like a milky suspension, hence the name.
4. Half life of the particles is about 10 minutes
5. The apolipoproteins of chylomicrons include apoB-48 (unique to this class of lipoproteins), apoE, and apoC-II
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13. VLDL-Very low density lipoproteins
1. When the diet contains more fatty acids than are needed immediately as fuel, they are converted to triacylglycerols in
the liver and packaged with specific apolipoproteins into very-low-density lipoprotein.
2. Excess carbohydrate in the diet can also be converted to triacylglycerols in the liver and exported asVLDLs
3. VLDLs contain
 cholesterol
 cholesteryl esters,
 apoB-100, apoC-I, apoC-II, apoC-III, and apo- E
1. These lipoproteins are transported in the blood from the liver to muscle and adipose tissue, where activation of
lipoprotein lipase by apoC-II causes the release of free fatty acids from theVLDL triacylglycerols.
2. Adipocytes reconvert them to triacylglycerols, and store the products in intracellular lipid droplets
3. Myocytes oxidize the fatty acids to supply energy.
4. VLDL remnants are removed from the circulation by hepatocytes.
5. The uptake is receptor mediated and depends on the presence of apo E
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14. LDL- Low density lipoproteins
Removal of triacylglycerol fromVLDL produces low-density lipoprotein (LDL)
Very rich in cholesterol and cholesteryl esters and containing apoB-100 as their major apolipoprotein
Carry cholesterol to extrahepatic tissues that have specific plasma membrane receptors that recognize apoB-100.
Receptor mediated endocytosis:-
1. apoB-100, is recognized by specific surface receptor proteins, LDL receptors, on cells that need to take up cholesterol.
2. The binding of LDL to an LDL receptor initiates endocytosis.
3. The endosome fuses with a lysosome, which contains enzymes that hydrolyze the cholesteryl esters, releasing
cholesterol and fatty acid into the cytosol.
4. The apoB-100 of LDL is also degraded to amino acids that are released to the cytosol
5. LDL receptor escapes degradation and is returned to the cell surface, to function again in LDL uptake
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15. UPTAKE OF CHHOLESTEROL BY RECEPTOR MEDIATED ENDOCYTOSIS
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16. high-density lipoprotein (HDL)
1. Originates in the liver and small intestine, contain little cholesterol and no cholesteryl esters
2. HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins and the enzyme lecithin-cholesterol acyl
transferase (LCAT).
3. LCAT catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol.
4. LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of
chylomicron andVLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped
nascent HDL to a mature, spherical HDL particle.
5. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded; some of this cholesterol
is converted to bile salts.
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17. Mechanism of uptake of HDL by the liver
1. bind to plasma membrane receptor proteins called SR-BI
2. These receptors mediate partial and selective transfer of cholesterol and other lipids in HDL to the cell.
3. Depleted HDL then dissociates to recirculate in the bloodstream and extract more lipids from chylomicron andVLDL
remnants.
4. can also pick up cholesterol stored in extrahepatic tissues and carry it to the liver, in reverse cholesterol transport
pathways.
5. apoA-I in depleted HDL interacts with an active transporter, the ABC1 protein, in a cholesterol-rich cell.The apoA-I is
taken up by endocytosis, then resecreted with a load of cholesterol, which it transports to the liver.
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18. Fate of lipoprotein remnants
1. Chylomicrons andVLDL are degraded to protein-rich remnants.
2. Receptors in the liver bind to the apoE in the chylomicron remnants and mediate their uptake by endocytosis.
3. Both are taken up by the liver an further degraded in liver lysosomes.
4. The apoprotein is reused for synthesis of LDL, which is the principal form in which cholesterol is transported
and HDL plays important role in bringing the excess cholesterol back from the liver for metabolism and
excretion.
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REFERENCE
BOOKS:-
Principles of biochemistry -Lehninger 5th ed
Biochemistry – Mathews et.al
Outlines of Biochemistry – Conn and Stumpf

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