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Lipoprotein Overview
Lipoprotein Particle Structure
Apolipoprotein
Apolipoprotein Apolipoprotein
NONPOLAR
LIPID CORE
Cholesterol Ester
Triglyceride
POLAR
SURFACE COAT
Phospholipid
Free cholesterol
Lipoprotein Subclasses
5 10 20 40 60 80 1000
Diameter (nm)
1.20
1.10
1.06
1.02
1.006
0.95
Den
sity
(g
/ml)
HDL2
HDL3
Chylomicron
Remnants
VLDL
IDL
Chylo-
microns
Lp(a)
LDL
Lipoprotein Classes
Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000;149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.
HDLLDLChylomicrons,VLDL, and
their catabolic remnants
> 30 nm 20–22 nm 9–15 nm
D<1.006 g/ml D=1.019-1.063g/ml D=1.063-1.21 g/ml
Lipids Online
What do lipoproteins do?
Serve to transport lipid-soluble compounds
between tissues
Substrates for energy metabolism (TG)
Essential components for cells (PL, UC)
Precursors for hormones
Precursors for eicosanoids
Lipid soluble vitamins
Precursors for bile acids
The Players - Apolipoproteins
Apo AI (liver, small intestine)
Structural; activator of lecithin:cholesterol acyltransferase
(LCAT)
Apo AII (liver)
Structural; inhibitor of hepatic lipase; component of ligand for
HDL binding
Apo A-IV (small intestine)
Activator of LCAT; modulator of lipoprotein lipase (LPL)
Apo A-V (liver)
Direct functional role is unknown; regulates TG levels.
Apolipoproteins
Apo B-100 (liver)
Structural; synthesis of VLDL; ligand for LDL-
receptor
Apo B-48 (small intestine)
Structural; synthesis of chylomicrons; derived from
apo B-100 mRNA following specific mRNA editing
Apo E (liver, macrophages, brain)
Ligand for apoE receptor; mobilization of cellular
cholesterol
Apolipoproteins
Apo C-I (liver)
Activator of LCAT, inhibitor of hepatic TGRL
uptake
Apo C-II (liver)
Activator of LPL, inhibitor of hepatic TGRL uptake
Apo C-III (liver)
Inhibitor of LPL, inhibitor of hepatic TGRL uptake
Lipoprotein Metabolism
Exogenous/chylomicron pathway
(dietary fat)
Endogenous pathway (lipids
synthesized by the liver)
HDL metabolism (apolipoprotein
transfer, cholesteryl ester transfer,
reverse cholesterol transport
Lipoprotein Metabolism
Exogenous/chylomicron pathway
(dietary fat)
Endogenous pathway (lipids
synthesized by the liver)
HDL metabolism (apolipoprotein
transfer, cholesteryl ester transfer,
reverse cholesterol transport
Rutas Metabólica de las Lipoproteínas en Humanos
Lipoprotein Metabolism
Exogenous/chylomicron pathway
(dietary fat)
Endogenous pathway (lipids
synthesized by the liver)
HDL metabolism (apolipoprotein
transfer, cholesteryl ester transfer,
reverse cholesterol transport
Surface MonolayerPhospholipids (12%)Free Cholesterol (14%)Protein (4%)
Hydrophobic CoreTriglyceride (65%) Cholesteryl Esters (8%)
TG Rich: VLDL
Cholesterol and
Atherosclerosis, Grundy)
VLDL Biogenesis
Cholesterol and
Atherosclerosis, Grundy)
Microsomal
TG transfer
protein (MTP)Facilitates the
translocation, folding
of apoB and addition
of lipids to lipid
binding domains
TG and
cholesterol are
synthesized in
the liver as
VLDL which
contains apoB-
100
VLDL
Metabolism
Cholesterol and
Atherosclerosis, Grundy)
Apo C’s and apoE and
cholesteryl ester are
acquired from HDL in
circulation
Fatty Acid Transport
Cholesterol and
Atherosclerosis, Grundy)
ApoC-II activates
lipoprotein lipase which
catalyses the hydrolysis
of TG
VLDL
Metabolism
Cholesterol and
Atherosclerosis, Grundy)
Apolipoproteins are
transferred back to HDL
The end product is a
VLDL remnant (IDL)
Surface MonolayerPhospholipids (25%)Free Cholesterol (15%)Protein (22%)
Hydrophobic CoreTriglyceride (5%) Cholesteryl Esters (35%)
CE Rich: LDL
Cholesterol and
Atherosclerosis, Grundy)
LDL Metabolism
Cholesterol and
Atherosclerosis, Grundy)
Hepatic Lipase
Cholesteryl ester
transfer protein
LDL is removed by
apoB100 receptors
which are mainly
expressed in the
liver
LDL Cellular Metabolism
Cholesterol and
Atherosaclerosis, Grundy)
LDL are taken up by the LDL Receptor into clathrin-coated pits
LDL Cellular Metabolism
Cholesterol and
Atherosaclerosis, Grundy)
LDL dissociates from the receptor; the receptor recycles to the membrane
LDL Cellular Metabolism
Cholesterol and
Atherosaclerosis, Grundy)
In the lysosome, lipids are deseterified; proteins are hydrolyzed
LDL Cellular Metabolism
Cholesterol and
Atherosaclerosis, Grundy)
Increase in free cholesterol regulates decrease cholesterol synthesis
and uptake; increase cholesterol esterification
Lipoprotein Metabolism
Exogenous/chylomicron pathway
(dietary fat)
Endogenous pathway (lipids
synthesized by the liver)
HDL metabolism (apolipoprotein
transfer, cholesteryl ester transfer,
reverse cholesterol transport
Surface MonolayerPhospholipids (25%)Free Cholesterol (7%)Protein (45%)
Hydrophobic CoreTriglyceride (5%) Cholesteryl Esters (18%)
CE Rich: HDL
Cholesterol and
Atherosclerosis, Grundy)
HDL Subpopulations
Rye KA et al. Atherosclerosis 1999;145:227-238.
Apolipoprotein Composition
A-I HDL A-I/A-II HDL
A-II HDL
Particle Shape
Discoidal
Spherical
Lipid Composition
TG, CE, and PL
Particle Size
HDL2b HDL2a HDL3a HDL3b HDL3c
Lipids Online
HDL Maturation
Cholesterol and
Atherosclerosis, Grundy)
HDL is secreted in a
discoidal form from the liver
and gut.
As it acquires cholesterol
from tissues in the
circulation, it matures into a
spherical form through the
action of lecithin:cholesterol
acyl transferase
HDL MetabolismNascent HDL (lipid-poor apoA-I) is produced by the liver and intestine
Cholesterol Recycling
Cholesterol and
Atherosaclerosis, Grundy)