Transcript Lec5 Lipoproteins

Lipoproteins
The serum lipoproteins are complexes of lipids and specific proteins called
"apoproteins".
Functions of Lipoproteins
Help to transport lipids in blood. Since lipids
are water insoluble, they can't be transported
in blood. For their transport, they are conjugated
with apoprotiens forming lipoproteins which
are water soluble and can be transported in blood
Composition of lipoproteins:
Lipoproteins are composed of a neutral lipid
core (TAG and cholesterol ester) surrounded by a
shell of apoproteins, phospholipids and free
cholesterol, all oriented so that their polar
proteins are exposed to the surface of lipoprotein,
thus making the particle soluble in aqueous
solution.
Spherical molecules of lipids and proteins (apoproteins) =
amphipathic molecules
Outer coat:
- Apoproteins
- Phospholipids
- Cholesterol
(Unesterified)
Inner core:
- TAG
- Cholesterol ester
(CE)
Lipoprotein Structure
Apoproteins
• There are five major classes ( from A-E) of apoproteins
– divided by structure & function
– Each class has subclasses e.g. Apo A1, Apo CII
– Functions of apoproteins
• Some are required as structural proteins e.g.B48, B100
• Some are activators, e.g. Apo CII
• Some are recognition sites (recognized by the receptors and
help binding of lipoprotein to its receptors on cell surface
e.g. Apo E and Apo B
Types of Lipoproteins
• There are various types of
lipoproteins:
– They differ in lipid and protein
composition, therefore they
differ in: Size, density and apoprotein
content
• They are:
Chylomicrons (CM)
Very low density Lipoprotein VLDL)
Low density Lipoprotein (LDL)
High density Lipoprotein (HDL)
Chylomicrons (CM):
Synthesis: CM is synthesized in intestinal mucosal cells from
dietary TAG, cholesterol ester, phospholipids and apoprotein B48.
-Apoprotein B-48 is the structural apoprotein that is unique to
CM and synthesized in endoplasmic reticulum.
-Function:
CM carries dietary (exogenous) TAG and CE from intestinal
mucosal to blood
Metabolism of CM
-Nascent chylomicrons (TAG, CE, B48) travel through the lymph into the blood.
- Apo CII, the activator of lipoprotein lipase (LPL), and apo E are transferred
from HDL, and mature chylomicrons are formed.
-TAG is hydrolysed by the activated LPL into glycerol (which move to liver) and
free fatty acids which are carried by albumin to either adipose tissue (to be stored)
or to muscles (to be used as source for energy).
- The chylomicron remnants interact with receptors on liver cells (which are
recognized by apo E) and are taken up by endocytosis. The contents are degraded
by lysosomal enzymes, and the product (amino acids, fatty acids, glycerol,
cholesterol, and phosphate) are released into the cytosol.
CM metabolism
VLDL:
Synthesis: VLDL is synthesized in the liver. It contains apoprotein (apo B100) as structural apoprotein .
Function: VLDL transport endogenous lipids (synthesized TAG and CE) and
dietary CE from liver to blood.
-In blood, Apo CII and Apo E are transferred from HDL.
-Apo CII activates LPL which hydrolyses TAG into glycerol and free fatty
acids. VLDL is converted into VLDL reminant then to LDL.
LDL
- synthesis: LDL is produced in the circulation as the end product of VLDLs
Function: LDL transport mainly cholesterol ester from blood to peripheral
tissues that require cholesterol for membrane structure or steroid hormone synthesis.
-LDL reacts with receptors on various cells, is taken up by LDL-receptor –
mediated endocytosis (see next slide). The receptors are recognized by apo B100
-Inside cells, LDL is digested by lysosomal enzymes and free cholesterol is released
from cholesterol esters.
-The released free cholesterol is re-esterified by ACAT to CE and stored for use in
cell membrane structure or steroid hormone synthesis.
-High LDL indicates high plasma cholesterol and tend to deliver cholesterol to artery
walls. High blood LDL is associated with high incidence of heart attacks and strokes
so it is called: Bad cholesterol.
LDL: receptor-mediated endocytosis
Synthesis:
HDL is synthesized in liver and
intestine
Functions:
1- HDL is reservoir of Apo CII and Apo E
(transferred apoproteoins).
2- HDL transfer excess cholesterol from tissues to
liver to be excreted in bile as free cholesterol or
converted into bile acids or passed into intestine and
excreted with faces. This process is called “reverse
cholesterol transport.
- HDL is called Good cholesterol as it remove
excess cholesterol from arterial walls into liver to be
excreted. High blood HDL is associated with low
incidence of heart attacks and strokes
Synthesized TAG
and Choleserol
-Chylomicrons are the
lowest of lipoproteins in
density and the largest
in size, contain the
highest lipid (85-90%
TAG) and smallest
protein contents.
-VLDL contains 60%
TAG.
Neutral fat
(TG) %
Protein %
Phospholipid
%
Cholesterol %
Type of
apoprotein
CM VLDL
85-90
60
LDL
8
HDL
3
2
8
10
15
22
20
50
30
5
15
50
17
apo B
apo A-1
apo E
apo C
Apo B48 Apo B100
apo E
apo E
apo C
apo C
-LDL contains the
highest content of CE
(50%)
- HDL is the most
dense, contain the
lowest amount of lipid
and the highest of
protein (50%).
From the Table we can divide lipoprotein according to lipid
content into:
TAG-rich lipoproteins:
- Chylomicrons : transport dietary (exogenous) TAG
- VLDL: transport TAG of endogenous (hepatic) synthesis
Cholesterol-rich lipoproteins:
LDL: transport cholesterol from blood to peripheral
tissues/liver
HDL: transport cholesterol from tissues to liver
Abnormalities in lipoprotein metabolism
Type I hyperlipoproteinemia or familial lipoprotein lipase deficiency
Due deficiency of lipoprotein lipase or apo C-II
CM, VLDL and TAG are increased in plasma
Type II hyperlipidemia or Familial hypercholesterolemia
deficiency of functional LDL receptors
elevation of plasma cholesterol but plasma TG remains normal