For Medical, Paramedicals and Allied Health sciences students

1. Transportation of Lipids
/ Metabolism of
lipoproteins

2. Exogenous pathway
eg: Metabolism of Chylomicrons
&
Endogenous pathways
-Metabolism of VLDL, LDL&
- reverse cholesterol transportation:
HDL

3. Chylomicrons
Density
(g/mL)
Protein
%
CH
%
TG
%
PL
%
Apo
proteins
Site of
syn
Functions
< 0.95 2 4 85 9 Apo-A,
B48, C &
E
Intestine Transport of dietary TGs and
cholesterol esters from
intestine to peripheral tissues
and liver.

4. Chylomicron metabolism
Carry dietary TG, Ch & chE to the
peripheral tissues.
C-II & PL
+
A-II & C-III
-
-E
Thoracic duct
Some of the
PL
LDL receptor
protein (LPL)

5. Endogenous pathways
Very low density lipoproteins (VLDL ) / IDL
Density
(g/mL)
Protein
%
CH
%
TG
%
PL
%
Apo
proteins
Site of
syn
Functions
0.95 –
1.006
10 15 55 20 Apo-B100, C
&E
Liver Transports endogenous TGs
from liver to peripheral
tissues.

6. Transport endogenous Triglycerides, Cholesterol from liver to the peripheral tissues.
Half life is 1 -3hrs
Cholesterol Ester Transfer Protein - CETP Transfer of CE and TG b/w HDL & VLDL & LDL
TG

7. Low Density lipoprotein (LDL)
Density
(g/mL)
Protein
%
CH
%
CE
%
TG
%
PL
%
Apo
proteins
Site of
syn
Functions
1.006-
1.063
20 10 40 8 22 Apo-
B100
Plasma
VLDL
Transports cholesterol
from liver to peripheral
tissues.
50%

8. -E
CE
TG
TG
30%
70%
Half life is 2 days

9. Tissue uptake of LDL
LDL loaded with Cholesterol is taken up by peripheral
tissues by
1. LDL receptors mediated endocytosis
2. Scavenger receptors (macrophages
derived from monocytes) mechanisms
Clathrin
Maintain their cell membrane (All tissues)
Steroid hormone synthesis (adrenal cortex)
Bile acids synthesis (hepatocytes)

10. Transport Cholesterol from liver to the
peripheral tissues.
Receptors mediated endocytosis

11. Scavenger receptors / Receptor independent mechanism
Phagocytic macrophages (monocytes )
• It recognize LDL that has been modified –
oxidized LDL
• Uptake of oxidized LDL by macrophages in
the arterial wall is potentially dangerous
• Macrophages overloaded with CE are
called foam cells

12. Lipoprotein(a) not apoprotein-A
• Lp(a) is a LDLvariant containing a protein- apolipoprotein(a).
• It is attached to apo-B100 of LDL by a disulfide bond
• It is highly atherogenic & impairs fibrinolysis
• It is an important marker of CHD

13. Endogenous pathway
Metabolism of High-Density Lipoproteins
(HDL) /
Reverse cholesterol transport

14. Density
(g/mL)
P
%
C
%
CE
%
TG
%
PL
%
Apo
proteins
Site of
syn
Functions
1.063-
1.210
40 2 23 5 30 Apo-A,
C-II & E
Liver &
Intestine
1) Transports cholesterol from
peripheral tissues to liver.
2) Serves as a circulating reservoir of
Apo C-II & E
3) Transfers cholesteryl esters to VLDL
& LDL in exchange for TG & PL
from these particles
High-Density Lipoprotein
(HDL)
25%

15. Enzymes and Transfer Proteins Functions
Lecithin - Cholesterol Acyl transferase -
LCAT
Esterifies the cholesterol (Cholesterol→
Cholesterol ester) content of HDL to prevent it
from reentering the cells
Acyl-CoA: Cholesterol Acyl transferase-
ACAT
Formation of cholesterol esters in cells
ATP-Binding Cassette-1- ABC-1 Transfer of free CH from plasma membrane to
ApoA-1 (HDL)
Cholesterol Ester Transfer Protein - CETP Transfer of CE and TG b/w HDL & VLDL &
LDL
Phospholipids Transfer Protein -PLTP Transfers phospholipids b/w lipoproteins
Scavenger receptor class-B type-1-SR-B1 Multi ligand receptor that binds not only HDL
but VLDL & LDL also

16. LCAT: Lecithin-Cholesterol Acyl transferase
ABC-1 : ATP-binding cassette-1
SR-B1: scavenger receptor class B type-1
CETP: Cholesterol Ester Transfer Protein
ABC-1
Hepatic HDL receptor
+

17. Significance of reverse cholesterol transport
– Cellular & lipoprotein cholesterol is delivered back to the liver
– It prevents deposition of cholesterol in the tissues
– anti-atherogenic property of HDL to protect LDL from oxidation due to
the association of esterase enzyme paraoxanase with HDL
– Paraoxanase may destroy oxidized LDL
– HDL decreases the risk of coronary heart diseases

18. Disorders of lipoproteins
(Lipoproteinemias/ Hyperlipidemias )
(Frederick son classification of lipoproteinemias)

19. • It causes complex & different disease mechanism, it classified into
• Primary hyper-lipoproteinemia:
– is completely genetic disorders.
• Secondary hyper-lipoproteinemia:
– is manifested due to other disorders (Nephrotic syndrome, type-II
DM & cirrhosis of liver ) .
• Coronary & cerebral vessels are more commonly affected
• Deposition of lipid in subcutaneous tissue leads to xanthomas
HYPER LIPOPROTEINEMIAS
(Increased lipoproteins in the blood)

20. Lipoproteinemias Metabolic
Defect
Elevated -Lp CH TG Clinical feature
Type-I:Familial
lipoprotein lipase
deficiency
Lipoprotein
lipase & Apo
C-II
deficiency
chylomicrons N ↑↑ Eruptive
xanthoma,
hepatomegaly &
Abdominal pain
Type –IIA: Familiar
Hypercholesterolemia
LDL receptor
defect. Apo-B
↑se
LDL ↑↑ N Atherosclerosis,
CDA &
Xanthelesma
Type –IIB: Familiar
Hypercholesterolemia
Overproducti
on of Apo-B
LDL & VLDL ↑↑ ↑ Corneal arcus
Type-I, IV & V: Hyper triglyceridemia, Type-IIa: Hyper cholesterolemia, Type-IIb & III: combined Hyperlipidemia

21. Lipoproteinemias Metabolic
Defect
Elevated -Lp CH TG Clinical feature
Type –III: broad
beta disease
Apo-E & Apo-
CII
broad beta –
VLDL(LDL
& IDL)
↑↑ ↑ Palmar
xanthomas ,
atherosclerosis
Type-IV: Familiar
Hyper
triaglycerolemia
Overproduction
of VLDL& Apo
–C-II
↑sed VLDL ↑ ↑↑ Associated with
diabetes, heart
disease, obesity
Type-V : Combined
hyper lipidaemias /
hyper
triglyceridemia
Secondary to
other causes
↑sed VLDL &
chylomicrons
N ↑↑ Ischemic heart
diseases &
chronic
pancreatitis
Type-I, IV & V: Hyper triglyceridemia, Type-IIa: Hyper cholesterolemia, Type-IIb & III: combined Hyperlipidemia

22. Palmar xanthomas
(Effects the palms)
Corneal arcus
(Deposition of lipid in the peripheral
cornea)
Eruptive xanthoma,
(small yellow nodules associated
with deposition of TG . lesions and
bumps that appear on the skin)
Xanthelasma
(yellow plaques deposits under
the periorbital skin / near
canthus of eyelid)
Tuberous Xanthomas
(deposition of yellow plaqes with
TG& chol in tendons or elbows
&knees)
Acanthocytosis
Irregular shaped RBCs with spikes on
the outside

23. Lipoproteinemias Metabolic
Defect
Decreased -
Lp
CH TG Clinical feature
Abeta-
lipoproteinemia
Apo-48 ↓
& Apo B-
100 ↓↓sed
LDL is
completely
absent
(TG is not
incorporated
into VLDL &
Chylomicrons)
↓↓ ↓ -Malabsorption : causes
mental & physical
retardation.
-Acanthocytes
Familial α-lipo
protein deficiency
(Tangier’s disease)
- Mutation
in the
ABC-1
protein
-HDL↓↓↓ &
-A–I ↓
N N “CE”are accumulated in
tissues leads to
Increased risk of CAD
Large orange yellow
tonsils & muscle atrophy
Recurrent peripheral
neuropathies
HYPO LIPOPROTEINEMIAS
(Decreased lipoproteins in the blood)

24. Thank you