lipoproteins meadiators

1. LIPOPROTEINS
PESENTED BY :
MANJUNATH D

2.  Lipoproteins are biochemical assembly that contains
both proteins and lipids.
 Lipoproteins are made up of different molecules that
interact with water insoluble fats molecules and
transports those fats in the plasma.
 Lipids are insoluble in water, the problem of
transportation in the aqueous plasma is solved by
associating nonpolar lipids with amphipathic lipids and
proteins to make water miscible lipoproteins.
INTRODUCTION

3.  consist of a nonpolar core and a
single surface layer of
amphipathic lipids.
 The nonpolar lipid core
(triacylglycerol and cholesteryl
ester) and amphipathic
(phospholipids and cholesterol
)molecules.
 The protein moiety of a
lipoprotein is known as an
apolipoprotein or apoprotein.

4. Lipoproteins can be classified in three ways-
1. Based on density- They are separated by
Ultracentrifugation. Depending upon the
floatation constant, 5 major groups are identified.
(i) Chylomicons, Derived from intestinal absorption of
triacylglycerol and other lipids. Transports
exogeneous triglycestrides ,from intestine to the
liver.
(ii) Very low density lipoproteins (VLDL), Derived from
the liver for the export of triacylglycerol.
Transport of triglycerides from the liver to tissues
for storage and energy.

5. 1) Based on density (contd.)
(iii) Intermediate density lipoproteins (IDL) are
derived from the catabolism of VLDL.
(iv) Low-density lipoproteins (LDL), representing a
final stage in the catabolism of VLDL. Transports
cholesterol to peripheral tissues.
(v) High-density lipoproteins (HDL), involved in
cholesterol transport and also in VLDL and
chylomicron metabolism. Transports cholestrol
away from the peripheral tissues to the liver.

6. As the lipid content
increases ,density
decreases and size
increases, that is why
chylomicrons are
least dense but
biggest in size, while
HDL are rich in
proteins, hence most
dense but smallest in
size.

7. 2) Based on electrophoretic
mobilities
Lipoproteins may be separated
according to their electrophoretic
properties into - α, pre β, β, and
broad beta lipoproteins.
The mobility of a lipoprotein is
mainly dependent upon protein
content.
Those with higher protein content
will move faster towards the anode
and those with minimum protein
content will have minimum mobility.

8. 3) Based on nature of Apo- protein content
 One or more apolipoproteins (proteins or
polypeptides) are present in each lipoprotein.
 The major apolipoproteins of HDL (α-lipoprotein) are
designated A.
 The main apolipoprotein of LDL (β -lipoprotein) is
apolipoprotein B (B-100), which is found also in
VLDL.
 Chylomicons contain a truncated form of apo B (B-
48) that is synthesized in the intestine, while B-100
is synthesized in the liver.
 Apo E is found in VLDL, HDL, Chylomicons, and
chylomicron remnants.

9. • Locate in extracellular on the
walls of blood capillaries,
anchored to the endothelium.
• Hydrolyze triglyceride (TG) in
the core of CM and VLDL to
free fatty acids and glycerol.
• The free fatty acids are
transported into the tissue,
mainly adipose, heart, and
muscle (80%), while about 20%
goes indirectly to the liver.
 LPL (Lipoprotein Lipase)

10. • Bound to the surface of liver cells, Hydrolyzes TG
to free fatty acids and glycerol
• Unlike LPL, HL does not react readily with CM
or VLDL but is concerned with TG hydrolysis in
VLDL remnants and HDL metabolism.

13. Apolipoproteins
LpL inhibitor;inflammatory signaling
pathways.
apoC-III
LpL activator.apoC-II
Inhibit Lp binding to LDL R; LCAT activatoapoC-I
apoB-48
Structural protein of all LP except HDL.
Lacks receptor-binding domain of B 100.
apoB100
Tg metabolism;LCAT activator.apoA-IV
HL activationapoA-II
HDL structural protein; activates LCAT.apoA-I

14. (1) They can form part of the structure of the
lipoprotein, e.g. apo B, structural component of
VLDL and Chylomicons
(2) They are enzyme cofactors, e.g. C-II for
lipoprotein lipase, A-I for lecithin: cholesterol acyl
transferase (LCAT), or enzyme inhibitors, eg, 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, e.g. apo B-100
and apo E for the LDL receptor, apo A-I for the
HDL receptor.

15. Metabolism of chylomicrons

16. Metabolism of VLDL and LDL

19. LDL-R
Apo
b

20. Lipoprotein –related diseases
Disorder Defect Comments
Wolman
diseases(cholesteryl
ester storage
disease)
Defect in lysosomal
cholesteryl ester
hydrolase;affects
metabolism of LDLs.
Reduced LDL clearance
leads to
hypercholesterolemia,
resulting in atherosclerosis
and coronary artery
disease.
Tangier disease Reduced HDL
concentrations,noeffect
on chylomicron or VLDL
production.
Tendency to
hypertriglycerideemia;some
elevation in
VLDLs;hypertrophic tonsils
with orange appearance.

21. Lipoprotein –related diseases
Disorder Defect Comments
Heparin-
releasable hepatic
triglyceride lipase
deficiency
Deficiency of the
lipase leads to
accumulation of TG-
rich HDLs and VLDL
remnants (IDLs)
Causes xanthomas
and coronary artery
disease.
LCAT deficiency
Norum disease
Absence of LCAT
leads to inability
of HDLs to take
up cholesterol .
Decrease levels of
plasma cholesteryl
esters and lysolecithin.

22.  Lipoproteins are an important class of
biomolecules that have diverse functions.
 Their association with lipids for the purpose
of transport and storage make them a vitial
part of lipid function.
 Lipoproteins serve as excellent markers for
cardivascular diseases and other lipid related
disorders.