LIPOPROTEIN TYPES

AND TRANSPORT
 LIPOPROTEINS

What are lipoproteins and why do we need them?

Lipoproteins are a handful of different molecules

that interact with water insoluble fat molecules,
and transports those fats in the plasma
The textbook describes the lipoproteins as oil
tankers
Different lipoproteins are responsible for the
transportation of different fats
Lipoproteins allow fat to be dissolved into the
plasma
 LIPOPROTEIN FUNCTION

Transport lipids in plasma by the

protein portion (keep lipids soluble)
Transporting their lipid content to &
from tissues

N.B. In humans, the transport system is less

perfect than in other animals cholesterol
deposition in tissues atherosclerosis
 COMPOSITION OF PLASMA
LIPOPROTEINS

Neutral core (TAG, exogenous or de

novo, cholesterol esters)
Amphipathic apolipoprotein
Phospholipids
Cholesterol
 TRANSPORT OF CHOLESTEROL AND
LIPOPROTEIN

Chylomicron Transpot TAG From

Cholesterol diet

Lipoprotein

Transpot TAG From

VLDL, LDL, HDL
Cholesterol liver
 Cholesterol

Found only in animals

Important component of membranes, steroid
hormones, bile and Vitamin D

Exogeneous cholesterol comes from diet

Endogeneous cholesterol is synthesized by the
liver

70 % of cholesterol associated with cellular

components
30 % is in the plasma ( free form , esterfied )

Transported by HDL and LDL
 Apoliproproteins

Outer protein shell of the lipoprotein

molecule

The protein lipid interaction allows the

water insoluble lipid to become soluble in
plasma

The apolipoprotein is responsible for the

interactions with cell membranes and
enzymes to transport lipids to specific
locations
 APOLIPOPROTEINS

ApoA-I, II and IV
ApoB-48 and 100
ApoC-I, II and III
ApoD
Cholesterol ester transfer protein
ApoE
ApoH
APOLIPOPROTEINS
 APOLIPOPROTEIN A-I

ApoA-I synthesized in intestine and

liver

Associated with chylomicrons and

HDL
 APOLIPOPROTEIN A-II

Exchangeable apolipoprotein

Associated with HDL

 APOA-I AND II BIND TO HDL

HDL, highest density lipoprotein due to its

protein lipid ratio

Contains almost no cholesterol or

cholesterol esters when synthesized

Obtains cholesterol esters from

cholesterol by the HDL associated
enzyme, lecithin: cholesterol
acyltransferase (LCAT)
 LCAT
LCAT is synthesized in the liver
LCAT makes cholesterol esters from free
cholesterol found in chylomicron remnants
and VLDL remnants

LCAT transfers a fatty acid from the C-2

position of lecithin to the C-3-OH of
cholesterol, generating a cholesterol ester and
lysolecithin

The action of LCAT requires interaction with

ApoA-I
 LIPOPROTEIN TYPES AND
TRANSPORT

Function: Transport of fat soluble

substances

Types: 1) Chylomicron

2) VLDL

3) LDL

4) HDL
 CHYLOMICRONS

Made by: the small intestines in the fed state

Absorbed into: the lymph vessels, then -->
moves into the blood

Rich in: TAGs

Function: deliver energy-rich triacylglycerol

(TAG) to cells in the body cells to be used as
fuel
 CHYLOMICRON

Triglycerides

3 Fatty Acids Glycerol

Adipose Skeletal Heart Blood

(storage) Muscle (energy)
(energy)
Liver

Chylomicron Remnant

Liver
 VLDL

= Very Low Density Lipoprotein

Made in: the liver from excess dietary
carbohydrate and protein along with the
Chylomicron remnant
Secreted into: the bloodstream
Rich in: TGs - triacylglycerol
Function: Deliver TGs to body cells
Contains apo B100
Similar to Chylomicrons, but made by
different tissues
 Notes: triacylglycerol

TAG is stripped from chylomicrons and VLDL

through the action of lipoprotein lipase, an
enzyme that is found on the surface of
endothelial cells. This enzyme digests the TAG
to fatty acids and monoglycerides, which can
then diffuse into the cell to be oxidized, or in
the case of an adipose cell, to be re-
synthesized into TAG and stored in the cell.
 VLDL

Triglycerides

3 Fatty Acids Glycerol

Adipose Skeletal Heart Blood

(storage) Muscle (energy)
(energy)
Liver

Once VLDL looses much of its TGs it becomes LDL

 LDL

= Low Density Lipoprotein

Made in: the Liver as VLDL

Arise from: VLDL once it has lost a lot of its
TGs
Secreted into: the bloodstream
Rich in: Cholesterol

Function: Deliver cholesterol to all body cells

 LDL

As VLDL particles are stripped of triacylglycerol, they

become more dense. These particles are remodeled at
the liver and transformed into LDL.

The function of LDL is to deliver cholesterol to cells,

where it is used in membranes, or for the synthesis of
steroid hormones (blue pathway). Cells take up
cholesterol by receptor-mediated endocytosis. LDL
binds to a specific LDL receptor and is internalized in an
endocytic vesicle. Receptors are recycled to the cell
surface, while hydrolysis in an endolysosome releases
cholesterol for use in the cell.
 HDL

= High Density Lipoprotein

Made in: the Liver and Small Intestine

Secreted into: the bloodstream

Function: Pick up cholesterol from body

cells and take it back to the liver = reverse
cholesterol transport
Potential to help reverse heart disease
NORMAL CHOLESTEROL METABOLISM

Key concepts: synthesis

Primary synthetic sites are extrahepatic, but liver is
key regulator of homeostasis
Key concepts: absorption
Largest source is biliary secretion, not diet.
Normal absorption: 50%
For cholesterol to be absorbed it must:
undergo hydrolysis (de-esterification by esterases)
be incorporated into micelles
be taken up by cholesterol transporter
be re-esterified and incorporated into
chylomicrons
NORMAL TRIGLYCERIDE METABOLISM

Key concepts: absorption

Triglyceride (i.e. energy) assimilation is key to

the survival of the organism.
Dietary triglyceride must be hydrolyzed to
fatty acids, mono-glycerides and glycerol
prior to absorption.
Fatty acids must partition to micellar phase
for absorption.
For transport, triglyceride must be
reconstituted from glycerol and fatty acid
and incorporated into chylomicrons.
 TRIGLICERIDES
Glycerol with 3 attached fatty acids

Exogenesis source : Dietary

Endogeneous : Liver and tissue storage

95 % of body fat is triglycerides

Energy source when plasma glucose is decreased
Triglyceride catabolism is regulated by lipase,
epinephrine and cortisol

Triglycerides transported by Chylomicrons

(exogeneous) and VLDL (endogenous)
THE NORMAL FAT-TRANSPORT TASKS

Lipid in plasma

Cholesterol and phospholipids - represent

2/3 of the plasma lipid, - slower turnover
than fatty acids

The major fat-transport tasks are movement

of free fatty acids and fatty acid esters of
glycerol (glycerides)
 LIPOPROTEIN TOP 10 - RESUME

Lipoproteins transport various lipids ( fats ) thru plasma to different

locations
High relationship between specific lipoproteins and CAD
Apolioproteins are the protein shells that interact with lipids and allow
them to be water soluble

HDL ( Good Cholesterol ) transports cholesterol away from tissues to

the liver
LDL ( Bad Cholesterol ) transports cholesterol to the tissues from the
liver
VLDL transports endogenous triglycerides from liver to tissues
Chylomicrons transport exogenous triglycerides from GI tract to liver

Accurate Lipoprotein testing requires a fasting specimen

LDL is not directly measured , but calculated from the Friedwald

Calculation

LDL CHOL - ( HLD VLDL ) 29

 ATHEROSCLEROSIS

HDL and ApoA-I negatively correlated with

atherosclerosis
ApoA-II positively correlated with
atherosclerosis
Deposits of fat and cholesterol building up
in lining of arteries
Atherosclerosis->cardiovascular heart
disease
 HOW HDL PREVENTS
ATHEROSCLEROSIS

HDL transports cholesterol from

peripheral tissues to liver for catabolism

LCAT converts cholesterol into

cholesterol esters

ApoA-I needs to be bound to HDL to

activate LCAT
 CONCLUSION

Helps prevent
ApoA-I HDL Activate LCAT
atherosclerosis

ApoA-I

Leads to higher
Does not activate
ApoA-II Levels of
LCAT
Atherosclerosis

HDL