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Abdul Salam M.

Sofro
Faculty of Medicine
YARSI University

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

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

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

Sites of action of the phospholipases A1, A2, C and D.

Phospholipid Structures
Phosphatidylcholine (PC)

Phosphatidylethanolamine (PE)

Phosphatidylserine (PS)

Cont.

Chylomicron derived from intestinal absorption


of TAG
Very Low Density Lipoproteins (VLDL of pre-lipoproteins) derived from the liver for export of
TAG
Low Density Lipoproteins (LDL or -lipoproteins)
representing the final stage in the catabolism of
VLDL
High Density Lipoproteins (HDL) or -lipoproteins)
involved in VLDL & chylomicron metabolism and
also in cholesterol transport

Function of lipoproteins

Chylomicrons
Transport triacylglycerols from intestines to other
tissue except kidneys

VLDL
Bind triacylglycerols in liver and carry them to fat
tissue

LDL
Carry cholesterol to peripheral tissues

HDL
Bound to plasma cholesterol. Transport cholesterol
to liver

Composition of lipoproteins in human plasma


Fraction

Source

Chylomicro
ns
Chylomicro
n
remnants
VLDL
IDL
LDL

Intestine
Chylomicrons

1-2
6-8

98-99
92-94

88
80

Liver
(intestine)
VLDL
VLDL

7-10
11
21

90-93
89
79

56
29
13

32
33
57
70

68
67
43
30

2
16
13
-

HDL1
HDL2
HDL3
Pre--HDL

Liver &
intestine
VLDL
Chylomicrons

Protein Total lipid


(%)
(%)

TAG
(%)

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 freely
transferable between several different lipoproteins
Apo E (arginine rich) are present in VLDL & HDL

Apolipoproteins of human plasma


lipoproteins
Apolipoprotein
s

Lipoproteins

Molecular
Mass (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,

34,000

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

TAG is transported from the intestines in


chylomicrons and from the liver in VLDL.
Chylomicrons are found in chyle formed by the
lymphatic system draining the intestine and
responsible for the transport of all dietary lipids
into the circulation.
Smaller & denser particles having the physical
characteristics of VLDL are also to be found in
chyle. Their formation occurs even in the
fasting state, their lipids originating mainly from
bile & intestinal secretion

Chylomicrons & VLDL are rapidly


metabolized. Larger particles are
catabolized more quickly than smaller
ones.
Liver does not metabolize native
chylomicrons or VLDL significantly
TAG of chylomicrons & VLDL are
hydrolyzed by lipoprotein lipase located
on the walls of blood capillaries

The action of lipoprotein lipase (results in the


loss of approx. 90% of TAG of chylomicron &
the loss of Apo C) forms remnant lipoproteins
or chylomicron remnant.
Liver is responsible for the uptake of remnant
lipoproteins, mediated by a receptor specific
for Apo E.
LDL is metabolized via the LDL receptor
HDL takes part in both lipoprotein TAG &
cholesterol metabolism

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 and
synthetizing TAGs & phospholipids
It converts FA to ketone bodies
(ketogenesis)
It plays an integral part in the synthesis &
metabolism of plasma lipoprotein.

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

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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