Lipoproteins are complexes of lipids and proteins essential for transporting lipids in blood, with apolipoproteins serving as their protein component. Various types of lipoproteins, such as chylomicrons, VLDL, LDL, and HDL, perform specific functions in lipid transport and metabolism, while disorders in lipoprotein metabolism can lead to dyslipoproteinemia. Cholesterol biosynthesis is regulated with HMG-CoA reductase being the key enzyme, producing cholesterol for vital functions including hormone synthesis and vitamin D formation.

1. Lipoproteins
- Lipoproteins are lipids (triacylglycrol,cholesterol
ester,phospholipid,free cholesterol) combined with proteins
(Apolipoproteins orApoproteins).

2. Lipoproteins
-
Lipoproteins are lipids combined with proteins
.
Importance of lipoproteins formation
1- Lipids are water insoluble substance and can not be trasported in an aqueous
medium (blood plasma ).
2- in order to transport lipids between blood and different tissues they are
associated with a protein to form water soluble complex “plasma lipoproteins “
3- This protein fraction is synthesized in the liver and intestinal mucosa and called
apoprotein (apolipoprotein).
4- Failure of liver to synthesize apoprotein prevents mobilization of fat from liver causing
fatty liver .

3. Apolipoproteins or Apoproteins
They are the protein moiety of lipoproteins. They account for about 60% in HDL and only
1% in chylomicrons.
Some of these apoproteins are integral and cannot be removed and others are peripheral
i.e. they are free to transfer to other lipoproteins.
Types of Apoliporproteins:
:
Five types of apolipoprotiens are known
Apolipoprotein A: There are Apo-A-I, Apo-A-II and Apo-A-IV. They are present in HDL lipoproteins (-
lipoproteins ).
Apolipoprotein B: They are Apo-B- 48 and Apo-B-100. Apo-B-48 is present in chylomicrons and
chylomicron remnants. Apo-B-100 is present in VLDL, LDL and IDL .
Apolipoprotein C: They are Apo-C-I, Apo-C-II and Apo-C-III. All of them are present in VLDL,
HDL and chylomicrons.
Apolipoprotein D: It is present in the subfraction of HDL
Apolipoprotein E: It is present in VLDL, HDL, chylomicrons and
chylomicron remnants
.
.

4. Functions of Apolipoproteins:
1) Enzyme activators:
e.g. Apo-C-II for lipoprotein lipase and Apo-A-I and
Apo-C-I activates lecithin: cholesterol acyl
transferase(LCAT).
2) They actas ligands forinteraction with lipoprotein receptors
in tissues e.g. Apo-B-100 and Apo-E for LDL receptors,

5. Fractions of plasma lipoproteins:
- Five groups of plasma lipoproteins are present. These are:
1) Chylomicrons.
2) Very low density lipoprotein (VLDL, or pre--lipoprotein).
3) Low density lipoprotein (LDL, or -lipoprotein).
4) High density lipoprotein (HDL or -liporotein).]
5) Free fatty acids.
Methods of separation:
1-By electrophoresis:
2-Ultra-centrifugation:
Ultracentrifugation Electrophoresis
Chylomicrons, nonmobile
-lipoproteins
pre-lipoproteins
-lipoproteins
Albumin-free fatty
acids complex
+
_
Chylomicrons
-lipoproteins, LDL
pre-lipoproteins, VLDL
-lipoproteins, HDL
Albumin-free fatty
acids complex

7. Types of lipoproteins:
1- Chylomicrons:
Site of synthesis: Intestinal mucosa.
Function: They carry triglyceride, cholesterol ester and
phospholipids from the intestine(exogenous lipid) to the
peripheral tissues.
Apoproteins: Apo-B48, Apo-C II, Apo-E, and Apo-A.
Main lipid component: triglycerides.
Catabolism: It occurs in the plasma by lipoproteins lipase enzyme
which is activated by Apo-C-II.
The enzyme acts on triglycerides converting them into glycerol
and fatty acids.
The chylomicron remnants are taken up by the liver.
*lipoprotein lipase (plasma- clearing factor):
-Lipoprotein lipase is localized on endothelial cells of blood
vessels
- Removal of most of the lipid in chylomicrons by lipoprotein
lipase leaves chylomicron remnants .

9. 2-Very low density lipoproteins (VLDL):
Site of synthesis: Liver
Function: It carries triglycerides from the liver(endogenous lipid)
to extrahepatic tissues.
Apoproteins:Apo-C II, Apo-E, and Apo-B100.
Main lipid component: triglycerides.
Catabolism: It is catabolized in the plasma by lipoprotein lipase
It acts on triglycerides leading to formation of intermediate
density lipoproteins (IDL) which is further changed into low
density lipoproteins (LDL).

11. 3-Low density lipoprotein (LDL or -lipoprotein):
Site of synthesis: It is synthesized from VLDL in the circulation
and also in the liver.
Function: It carries cholesterol to various tissues.
Main lipid component: Cholesterol.
Apoproteins: Apo-B100.
Catabolism: It occurs through LDL-receptors.
LDL has specific receptors in the tissues such as liver, suparenal
cortex, ovary and testis.
LDL-receptors allow the cells to uptake and metabolize plasma
LDL.
Deficiency of these receptors leads to severe
hypercholesterolaemia.
Estrogen (female sex hormone) increases the number of LDL-
receptors in the liver, so it decrease blood cholesterol in females

12. 4-High density lipoprotein (HDL or -Lipoprotein):
Site of synthesis: Intestine and Liver.
Function: 1-It carries cholesterol from tissues to the liver to be
catabolized, this is called reverse cholesterol transport.
Main lipid component: Cholesterol ester and phospholipids.
Apoproteins: Apo-A, Apo-C, Apo-E, and Apo-D.

13. High density lipoprotein (HDL or -Lipoprotein):
Site of synthesis: Intestine and Liver
.
Function: It carries cholesterol from tissues to
the liver to be catabolized, this is called reverse
cholesterol transport
.
Main lipid component: Cholesterol ester and
phospholipids
.
Apoproteins: Apo-A, Apo-C, Apo-E, and Apo-D
.
It is the site of action of lecithin cholesterol
acyltransferase enzyme (LCAT
.)
Deficiency of HDL leads to accumulation of
cholesterol in the tissues (Tanger’s disease
.)

14. Cholesterol Metabolism
Biosynthesis of cholesterol:
Site and carbon source:
- cytosol
- All carbon atoms of cholesterol are derived from acetyl-CoA,
- Steps:
Formation of mevalonate from acetyl-CoA:
CH2 C SCoA
O
C
CH3
O
Acetoacetyl-CoA
CoASH
Thiolase
2 Acetyl-CoA
CoASH
H2O
CH3 C SCoA
O
CH2 C SCoA
O
C
CH3
OH
3-Hydroxy-3-Methyl-
Glutaryl-CoA, HMG-CoA
CH2 COOH
HMG-CoA
Synthase
HMG-CoA
Reductase
Acetyl-CoA
CH3 C SCoA
O
2 NADPH.H+
2 NADP + CoASH
CH2 CH2
C
CH2
OH
CH3
OH
HOOC
Mevalonate
Regulation of cholesterol biosynthesis:
Key regulatory enzymes:
- HMG-CoA reductase reaction is the rate-limiting step in
cholesterol biosynthesis.

15. Functions of cholesterol:
1-Vitamen D formation
2-bile acid and salts
3-male and female sex hormones
4-adrenocortical hormones

16. Dyslipoproteinemia
• Dyslipoproteinemia, also referred to as dyslipidemia,
encompasses a range of disorders of lipoprotein lipid
metabolism that include both abnormally high and low
lipoprotein concentrations, as well as abnormalities in the
composition of these lipoprotein particles

17. Dyslipoproteinemia