Transcript Slayt 1 - Cumhuriyet University

Lipoproteins
• Function: Transport of fat soluble substances
• Types:
1) Chylomicron
2) VLDL
3) LDL
4) HDL
Lipoprotein
class
Density
(g/mL)
Diameter
(nm)
Protein % Phospho Triacylglycerol
of dry wt lipid %
% of dry wt
HDL
1.063-1.21
5 – 15
33
29
8
LDL
1.019 –
1.063
18 – 28
25
21
4
IDL
1.006-1.019 25 - 50
18
22
31
VLDL
0.95 –
1.006
30 - 80
10
18
50
chylomicrons
< 0.95
100 - 500
1-2
7
84
Apolipoproteins: specific lipid-binding proteins that attach to the surface
intracellular recognition for exocytosis of the nascent particle
after synthesis
activation of lipid-processing enzymes in the bloodstream,
binding to cell surface receptors for endocytosis and clearance.
Main lipid components: triacylglycerols, cholesterol esters, phospholipids.
Major lipoproteins:
chylomicrons
very low density lipoproteins (VLDL)
low density lipoproteins (LDL)
high density lipoproteins (HDL)
Subfraction: intermediate density lipoproteins (IDL)
Electrophoretic mobility (charge):
HDLs =  lipoproteins
LDLs = - lipoproteins
VLDLs = pre- lipoproteins (intermediate between  and 
mobility).
I
N
T
E
S
T
I
N
E
Lymph system:
Chylomicrons
to capillaries
via lymph
chylomicron interacts
with lipoprotein lipase
removing FFA
Nascent chylomicrons acquire
apo CII (C) and E
(E) from HDL
non-hepatic tissues
CE
CE
CECE
CE
CECE
CE CE
ApoB48 aids
with chylomicron
assembly
Figure 3. Exogenous pathway of lipid transport.
Chylomicrons carry dietary fatty acids to tissues
and the remnants take cholesterol to the liver
LIVER
Triacylglycerol
in core
Chylomicron (or VLDL)
To Liver
Apo CII
LIPOPROTEIN LIPASE
Glycerol
Free fatty acids
Polysaccharide
Chain
Capillary
Endothelial
Surface of cell
In cellulo (muscle & adipose)
Free fatty acids
Figure 4. Lipoprotein lipase action on chylomicron triacylglycerol (an
identical reaction occurs with VLDL)
I
N
T
E
S
T
I
N
E
Lymph system:
chylomicron interacts
with lipoprotein lipase
removing FFA
chylomicron
acquires apo
CII (C) and E
(E) from HDL
non-hepatic tissues
CE
CE
CECE
CE
CECE
CE CE
C
E
ApoB48
chylomicron
remnants lose
CII to HDL
E
C
E
E C
EE E
Liver: apo E receptor
takes up remnants to
deliver cholesterol
LIVER
Figure 3. Exogenous pathway of lipid transport. Chylomicrons carry dietary fatty
acids to tissues and the remnants take cholesterol to the liver
B100 (B) helps
assemble and export
nascent VLDL
nascent VLDL acquires
apo CII (C) and apo E
(E) from HDL
LPL hydrolyze TAGs; FFA
uptake; LDL circulate to tissues
non-hepatic tissues
LIVER
CE
bile acids
Cholesterol
uptake;
excreted as
bile acids
Apo E binds
liver receptor
CE
CE CE
CE
CE
CE
CECE
CII and E release to HDL
apo B100 on LDL bind
to receptor
B B
CE
CE
B
B
B
B BB
B BB
LDL taken into the cell
to deliver cholesterol
HDL
scavenge
cholesterol
Figure 5. The liver-directed endogenous pathway
of lipoprotein metabolism.
Chylomicrons:
Exogenous Pathway
Fig. 6 Chylomicron Processing and Interface with HDL
Nascent Chylomicron
Assembly in Gut
Mediated by B48
HDL: Both Pathways
B48
E
E
A1
CII
E
E B48 apo E & CII
CII
from HDL
Mature Chylomicron
Apo E and CII
added from HDL
E
CII activates LPL
E
CII
B48
CII
Nascent HDL
Assembled in liver
Loans apo E/ apo CII
to nascent chylomicrons
Lipoprotein Lipase
capillary walls
hydrolyzes TAG
deliver FFA into adipose/muscle
CII
CII
Chylomicron Remnant
from mature chylomicron
apo CII returned to HDL
adipose &
muscle
FFA
apo CII
A1
CII
E
B48
CII
CII
Triacylglycerol
Mature HDL
CE from peripheral cells via
LCAT activated by apo A1
Apo CII returned by
chylomicrons
Cholesterol
ester
Phospholipid
sorting endosome:
ligand/receptor
dissociation
LDL
receptor
transport vesiclelysosome fuse forming
late endosome
Recycling
Recyclingofofreceptor
receptor
oand clathrin
clathrincoated pit
o
o
o
o
o
lysosome
late endosome
endocytosis
ACEH
CE  cholesterol
B100  amino
acids
vesicle
LDL
CE
NPC-1
mediated
transfer
free pool of
cholesterol
Membrane
Cholesterol
Cholesterol metabolism to
bile acids or steroids
Apo A1 receptor
L
C
A
T
CE in nascent HDL
ACAT (stimulated
by cholesterol)
CE stored in
Cholesterol droplets
CE CE
Esterase
Cholesterol release for
transport to liver
CERP
Figure 7. Cellular
cholesterol uptake,
metabolism and release.
Golgi
A1
CII
E
Reverse
Cholesterol
Transport
A1
E
CII
Apo A1 binds to receptor, activates
CERP to pump out cholesterol, and
LCAT to esterify cholesterol
Mature HDL:
Cleared by liver