Structure & function of IDL, Metabolism of IDL, Structure & function of LDL, Metabolism of LDL, Structure & function of HDL, Metabolism of HDL

1. METABOLISM OF LDL, IDL
AND HDL
Ashwathi Govind

2. content
• Structure & function of IDL
• Metabolism of IDL
• Structure & function of LDL
• Metabolism of LDL
• Structure & function of HDL
• Metabolism of HDL
• Reference

3. STRUCTURE OF IDL
Their size is in general 25 to 35
nm in diameter
They contain primarily a range of
TAG and cholesterol esters.
Contain multiple copies of the
receptor ligand ApoE in addition
to a single copy of Apo B100.

4. METABOLISM OF IDL
• Enable fats and cholesterol to move within
the water based solution of the
bloodstream.
• Each native IDL particle consist of protein
that encircles various lipids enabling as a
water soluble particle these lipids to travel
in the aqueous blood environment as part
of the fat transport system within the body.
• Promote the growth of atheroma.

5. IDL has two
competing
metabolic fates
Uptake by the
liver
Further
processing to
become LDL

6. • Formed from the degradation of VLDL as well
as HDL
lipoprotein lipase
• VLDL IDL LDL
TAG TAG + Apo E

7. METABOLISM OF LDL

8. * Bad cholesterol
cholesterol
* liver peripheral tissue
l

9. Synthesis of LDL

10. METABOLISM
LDL is taken
up by
peripheral
tissue by
receptor
mediated
endocytosis.
LDL receptor
are present in
all tissues.
But most
abundant in
hepatic cells
LDL receptors
are located in
specialized
regions called
clatherin
coated pits.
Binding of LDL
to receptor is
by apo B 100

11. LDL RECEPTORS
It is a polypeptide consists of 839 amino acids.
Contains extracellular and intracellular domains.
Extracellular domain is responsible for the clustering of LDL
receptors into regions of plasma membrane termed coated pits.
Apo B100 binds to Apo B100 receptor, receptor LDL complex is
internalized by endocytosis.

12. The endosome vesicle fuses with lysosomes.
The receptor is recycles and returned to the
cell surface.
LDL particles, Apo proteins and cholesterol
esters are hydrolyzed by hydrolases, forming
free amino acids and free cholesterol.
70% of LDL is degraded in the liver and
remaining is in extra hepatic tissues.
Free cholesterol incorporated into plasma
membrane or stored in cells.

14. FUNCTION OF LDL
75% of plasma cholesterol
is incorporated into LDL
particles.
LDL transport cholesterol
from liver to peripheral
tissues.
The transported
cholesterol has following
fates
• For synthesis of steroids
• May be incorporated into
membranes
• May be esterified to
MUFA and stored.

15. Clinical significance of LDL
LDL concentration is
increased in
cardiovascular diseases
Small fraction of
cholesterol is taken
up by macrophages.
Increased levels of
LDL or modified LDL
or oxidized LDL
increases the
fraction of
cholesterol taken by
macrophages.

16. There is an LDL infiltration
through arterial wall and
taken up by macrophages
or scavenger cells.
This is starting event
of atherosclerosis
leading to MI
Defects in LDL
receptor synthesis
leads to familial
hypercholesterolemia.

18. Structure of HDL

19. FUNCTION OF HDL
HDL transport cholesterol from peripheral tissues to liver,
called as reverse cholesterol transport
Cholesterol is excreted through bile
Cholesterol excretion needs prior esterification with PUFA
PUFA reduces serum cholesterol levels.

20. METABOLISM
Intestin
al cells
synthes
is
compo
nents
of HDL
and
release
into
blood
Nascen
t HDL
are
discoid
in
shape.
Free
cholest
erol is
taken
up by
the
HDL
Apo A 1
of HDL
activate
s LCAT.
LCAT
binds
to HDL
disc
Cholest
erol
from
cell is
transfer
red to
HDL by
cholest
erol
efflux
regular
protein,
which
is an
ABC
protein

21. Lecithin is
a
compone
nt of lipid
bilayer of
HDL disc.
Second
carbon of
lecithin
contains
PUFA
This PUFA
is
transferre
d to 3rd
OH group
of
cholester
ol to form
cholester
ol esters.
Cholester
ol esters
moves
into the
interior
of HDL
disc.
HDL
become
spherical
shape
with lot
of
cholester
ol are
formed
This is
called as
HDL-3

22. Mature HDL
are taken up
by the liver
cells by apo
A 1
mediated
receptor
mechanism.
HDL is taken
up by
hepatic
scavenger
receptor B1
Hepatic
lipase
hydrolyzes
HDL
phospholipid
and TAG.
Cholesterol
esters are
released into
liver cells.
These
cholesterol
esters are
used for the
synthesis of
bile acid or
excreted as
bile.

23. When HDL3
remains in
circulation,
cholesterol
esters from
HDL is
transferred
to VLDL,IDL
and LDL by a
cholesterol
ester transfer
protein(
CETP)
TAG from
VLDL,IDL and
LDL is
transferred
to HDL in
exchange for
cholesterol
esters
HDL particle
rich in TAG
and spherical
are called as
HDL2
These
particle are
first acted
upon by
hepatic
triglyceride
lipase (HTGL)
Efflux of
cholesterol
from
peripheral
cells to HDL
is mediated
by ABC
transporter
protein.

25. CLINICAL SIGNIFICANCE
Serum HDL levels
are inversely related
to the incidence of
MI
HDL levels <35
mg/dl increases risk
of CAD,>65mg/dl
reduce the risk of
CAD

27. Reference
• Lippincott’s; fifth edition; Richard A Harvey
• Biochemistry; debajyothi;13th edition
• Vasudevan & Sreekumari, Text book of
biochemistry for medical students.(6th Ed.).
• Biochemistry; Sathyanarayana,u Chakrapani.