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7/28/2019 Bm2-Lipid Transport and Storage
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Abdul Salam M. Sofro
Faculty of Medicine
YARSI University
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Learning objectives
• By the end of lectures, the students are
expected to:
– Understand lipid transport in the body (or the
blood plasma)
– Recognize various lipoprotein and the role of liver
in lipid transport and metabolism
– Understand lipid storage for energy reserve
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Lipid are insoluble in water
• How to transport in the blood plasma?
– Solved by associating non-polar lipid (TAG &
cholesteryl ester) with amphipathic lipids
(phospholipids & cholesterol) and protein to
make water-miscible lipoprotein
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Four major lipid classes are present in
lipoprotein
• Triacylglycerol (TAG)
• Phospholipids
• Cholesterol
• Cholesteryl ester
Another plasma lipid: Free Fatty Acids (FFA)
only 5% of the total FA present in the plasma
and the most metabolically active plasma lipid
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Sites of action of the phospholipases A1, A2, C and D.
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Phospholipid Structures
Phosphatidylcholine (PC)
Phosphatidylethanolamine (PE)
Phosphatidylserine (PS)
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Cont.
•
Chylomicron – derived from intestinal absorption of TAG
• Very Low Density Lipoproteins (VLDL of pre-β-
lipoproteins) – derived from the liver for export of TAG
• Low Density Lipoproteins (LDL or β-lipoproteins) –
representing the final stage in the catabolism of VLDL
• High Density Lipoproteins (HDL) or α-lipoproteins) –
involved in VLDL & chylomicron metabolism and also incholesterol transport
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Function of lipoproteins
•Chylomicrons
Transport triacylglycerols from intestines to othertissue – except kidneys
• VLDL
Bind triacylglycerols in liver and carry them to fattissue
• LDL
Carry cholesterol to peripheral tissues• HDL
Bound to plasma cholesterol. Transport cholesterolto liver
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Composition of lipoproteins in human plasma
Fraction Source Protein(%)
Total lipid(%)
TAG(%)
Chylomicrons
Chylomicron
remnants
VLDL
IDL
LDL
HDL1
HDL2
HDL3
Pre-β-HDL
Intestine
Chylomicrons
Liver (intestine)
VLDL
VLDL
Liver & intestine
VLDL
Chylomicrons
1-2
6-8
7-10
11
21
32
33
57
70
98-99
92-94
90-93
89
79
68
67
43
30
88
80
56
29
13
2
16
13
-
Albumin-FFA Adipose tissue 99 1 0
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Protein moiety of a lipoprotein is known as
apolipoprotein or apoprotein
• One or more apolipoproteins are present in
each lipoprotein:
– Apo A is major apoprotein of HDL
– Apo B is major apoprotein of LDL (Apo B-100), but is
found also in VLDL (Apo B-100) & chylomicrons
(Apo B-48)
–Apo C-I, C-II & C-III are smaller polypeptides freelytransferable between several different lipoproteins
– Apo E (arginine rich) are present in VLDL & HDL
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Apolipoproteins of human plasma lipoproteins
Apolipoproteins Lipoproteins MolecularMass (Da)
Apo A-I HDL, Chylomicrons 28,000
Apo A-II HDL, Chylomicrons 17,000
Apo A-IV Secreted with chyomicrons but
Transfer to HDL
46,000
Apo B-100 LDL, VLDL, IDL 550,000
Apo B-48 Chyloicrons, chylomicron remnants 260,000
Apo C-I VLDL, HDL, chylomicrons 7,6000
Apo C-II VLDL, HDL, chylomicrons 8,916
Apo C-III VLDL, HDL, chylomicrons 8,750
Apo D Subfraction of HDL 19,300
Apo E VLDL, IDL, HDL, Chylomicrons,
Chylomicron remnants
34,000
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Note:
• FFAs in the plasma arise from lipolysis of TAG
in adipose tissue or as a result of the action of
lipoprotein lipase during uptake of plasma
TAG into tissues. They found in combination
with albumin, rapidly metabolized to form
energy or esterified, the level may arise in
uncontrolled DM
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• TAG is transported from the intestines in
chylomicrons and from theliver
in VLDL.• Chylomicrons are found in chyle formed by the
lymphatic system draining the intestine andresponsible for the transport of all dietary lipids
into the circulation.
• Smaller & denser particles having the physicalcharacteristics of VLDL are also to be found in
chyle. Their formation occurs even in the fastingstate, their lipids originating mainly from bile &intestinal secretion
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• Chylomicrons & VLDL are rapidly metabolized.Larger particles are catabolized more quicklythan smaller ones.
• Liver does not metabolize native chylomicronsor VLDL significantly
• TAG of chylomicrons & VLDL are hydrolyzed by
lipoprotein lipase located on the walls of blood capillaries
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• The action of lipoprotein lipase (results in the
loss of approx. 90% of TAG of chylomicron &the loss of Apo C) forms remnant lipoproteinsor chylomicron remnant.
• Liver is responsible for the uptake of remnantlipoproteins, mediated by a receptor specificfor Apo E.
• LDL is metabolized via the LDL receptor
• HDL takes part in both lipoprotein TAG &cholesterol metabolism
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• Liver plays a central role in lipid transport &
metabolism:
– Facilitate digestion & absorption of lipids by
the production of bile
– It has active enzyme systems for synthesizing
& oxidizing FA aand synthetizing TAGs &
phospholipids
– It converts FA to ketone bodies (ketogenesis)
– It plays an integral part in the synthesis &
metabolism of plasma lipoprotein.
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Clinical aspects & others
• Imbalance in the rate of TAG formation & export
causes fatty liver when accumulation of lipid in
the liver becomes chronic, fibrotic changes occur
in the cell that progress to cirrhosis & impaired
liver function.
• Ethanol also causes fatty liver.
• Adipose tissue is the main store of TAG in the
body.
• Lipolysis is controlled by hormone-sensitive lipase
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• Increased glucose metabolism reduces the output of
FFA
• Insulin reduces the output of FFA fall in circulating
plasma FFA.• Several hormones promote lipolysis:
– Glucocorticoids
– Thyroid hormones
– Catecholamines
• Brown adipose tissue promotes thermogenesis.
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