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LIPOPROTEIN METABOLISM Darien Liew Daojuin


13 August 2017
CONTENTS
1. Lipids
2. Lipoproteins
3. Apolipoproteins
4. Fat metabolism
exogenous intestinal absorption
endogenous
reverse cholesterol transport
1. Association with atherosclerosis
2. Summary
LIPIDS
It comprises a group of naturally occurring molecules that include fats,
waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E, and K),
monoglycerides, diglycerides, triglycerides, phospholipids, and others.
NORMAL LIPID VALUES
LIPOPOROTEINS
INTRODUCTION

Large macromolecular complexes


composed of lipids and proteins that
transport poorly soluble lipids (primarily
triglycerides, cholesterol, and fat-soluble
vitamins) through body fluids (plasma,
interstitial fluid, and lymph) to and from
tissues.
Play an essential role in the
absorption of dietary cholesterol, long chain
fatty acids, and fat-soluble vitamins
the transport of triglycerides, cholesterol, and
fat-soluble vitamins from the liver to peripheral
tissues
the transport of cholesterol from peripheral
tissues to the liver and intestine.
What is apolipoproteins?
These are proteins associated with lipoprotein.

LIPOPROTEINS Function?
Involved in assembly, structure, function, and metabolism

CLASSIFICATION of lipoproteins.
Activate enzymes important in lipoprotein metabolism
and act as ligands for cell surface
receptors.
A breakdown of VLDL
will form IDL
APOLIPOPROTEINS
Apolipoproteins are
proteins that bind
lipids to form
lipoproteins.
They facilitate
lipoproteins to
transport lipids through
the lymphatic and
circulatory systems
APOLIPOPROTEINS
Because lipids are insoluble, apolipoproteins have detergent like
(amphipathic) properties, alongside phospholipids, can surround lipids,
creating a lipoprotein particle that is water soluble and can move
through the blood circulatory system.
Apolipoproteins also serve as enzyme cofactors, receptor ligands and
lipid transfer carriers that regulate the metabolism of lipoproteins and
their uptake in tissues.
APOLIPOPROTEINS
ENZYMES IN LIPID METABOLISM
FAT METABOLISM
1. Exogenous
2. Endogenous
3. Reverse cholesterol transport
Luminal Phase

Fat Solubilisation

Lipase Action

Absorption

Exocytosis
1. Exogenous source of lipid via
intestinal absorption.

2. From the lacteals to the blood


stream, chylomicrons are
modified by apolipoproteins
and hydrolysed by LPL on the
endothelium.

3. LDL remnants are rapidly


cleared in the liver by binding
to LDL receptos.

4. Secretion of VLDL by the liver,


rich in TG. Differ from
chylomicrons due to full length
Apo-B.

5. VLDL gets hydrolysed to


release TG which can form FFA.
This converts VLDL to IDL, and
cleared by the liver, by LDLR.

6. Some IDL gets converted to


LDL, by removing the TG and
other materials, except Apo
B100.
In dyslipoproteinamia
conditions, when there is a
defective LDLR (familial
hypercholesterolemia),
LDL accumulates in the blood
and is subjected to oxidation.

In hyperlipidemia, it can
cause endothelial injury,
lipoproteins accumulate
within the intima, and
generate oxidised LDL and
cholesterol crystals. In
addition, Apo B (in the LDL)
that can no longer be
cleared, triggers
inflammation foam cells.

More LDLs come by, coupled


with smooth muscle
recruitment, proliferation and
deposition of collagen, ECM
and lipid, this results in
atherosclerosis.
ASSOCIATION BETWEEN
HYPERLIPIDEMIA, ENDOTHELIAL Defective LDL Receptors
DYSFUNCTION AND ATHEROSCLEROSIS
Hyperlipidemia

Atherosclerosis
REVERSE
CHOLESTEROL
TRANSPORT
1. Lipid poor Apo A1, from the
liver and immature HDL accepts
cellular cholesterol and
phospholipids via ABCA1.

2. This produces HDL (contains


cholesterol) which can take in
more cholesterol from the cells,
via ABCG1.

3. Small HDL gets esterified by


LCAT, to maintain an uptake
gradiet and mature the HDL..
LOW DENSITY LIPOPROTEINS
LDL particles contain cholesterol, triglycerides, phospholipids, and
apolipoproteins B-100 and C-III.
Elevated plasma concentrations of apo B-100-containing lipoproteins
can induce the development of atherosclerosis even in the absence of
other risk factors.
It has been proposed that the initiating event in atherogenesis is the
subendothelial retention of apo B-100-containing lipoproteins via a
charge-mediated interaction with proteoglycans in the extracellular
matrix.
HIGH DENSITY LIPOPROTEIN
HDL particles, in contrast to LDL and VLDL particles, have
antiatherogenic properties that include
removal of cholesterol from macrophages (termed macrophage cholesterol efflux),
antioxidation,
protection against thrombosis,
maintenance of endothelial function, and
maintenance of low blood viscosity through an action on red cell deformability

So what about triglycerides?


TRIGLYCERIDES
Triglycerides role in atherosclerosis is likely because of
delayed clearance of triglyceride-rich lipoproteins on VLDL particles that carry apo C-
III or reduced lipoprotein lipase activity, which is common in insulin resistance,
the VLDL remnants may enter the vessel wall or be converted to small LDL particles.
Small LDL particles have conformational changes in apoB reduced LDL receptor-
mediated clearance allowing these particles to circulate for a longer duration where
they become susceptible to oxidation, glycation, and glyco-oxidation.

Further Reading
Further Reading

CETP
High concentrations of chylomicron remnants or VLDL particles result in lower levels
of HDL cholesterol, due to cholesterol ester transfer protein (CETP) mediating a
process of exchange HDL/LDL to VLDL/chylomicrons.

Triglyceride-enriched HDL particles have reduced macrophage cholesterol efflux


capacity. Triglyceride-rich lipoproteins increase endothelial activation, facilitate
monocyte infiltration into the arterial wall, and increase activation of pro-
inflammatory genes via AP-1

TG
HDL Cholesterol VLDL
Phospholipids
Estyl
SUMMARY
REFERENCES
UpToDate
https://www-uptodate-com.ezproxy.lib.monash.edu.au/contents/lipoprotein-
classification-metabolism-and-role-in-
atherosclerosis?source=see_link&sectionName=LIPOPROTEINS%20AND%20ATHERO
SCLEROSIS&anchor=H15#H16

Medscape
http://www.medscape.org/viewarticle/416521_2

Davidsons Principles and Practice of Medicine, 22nd Edition


Robbins Basic Pathology, 9th Edition