Lipoproteins

 Lipoproteins= Lipid + Apolipoproteins

 Transport lipids in plasma

 Classification:
1. Chylomicrons

2. Very low density lipoproteins (VLDL)

3. Low Density lipoproteins (LDL)

4. High density lipoproteins (HDL)

STRUCTURE
 Non-polar lipid core: contains triacylglycerol and
cholesteryl esters
 A single layer of amphipathic phospholipid and cholesterol
layer
 Their polar groups face outward to the aqueous medium
and interact with protein moieties
 Lipid content in lipoproteins:
 Maximum→ Chylomicrons
 Minimum→ HDL
 Triglyceride content in lipoproteins:
 Maximum→ Chylomicrons
 Minimum→ HDL
 Maximum exogenous/ dietary triglyceride→ Chylomicron
  Maximum endogenous triglyceride→ VLDL
 Cholesterol content in lipoproteins:
 Maximum→ LDL
 Minimum→ Chylomicron
 Phospholipid content in lipoproteins:
 Maximum→ HDL
 Minimum→ Chylomicron
 Protein content in lipoprotein:
 Maximum→ HDL (upto 70% in various HDL fractions)
 Minimum→ Chylomicron (1%)
 APOLIPOPROTEINS

 One or more apolipoproteins are present in each

lipoprotein; e.g. Apo-A, B, C, D, E
 The Distribution of Apolipoproteins Characterizes the
Lipoprotein
 Some apolipoproteins are integral and cannot be
removed (e.g. Apo-B)
 others are bound to the surface and are free to transfer
to other lipoproteins (Apo-C & Apo-E)
 CHARACTERISTICS
 Apolipoprotein : A to J [except F] & Apo(a)
 Genetically and structurally distinct
 Apolipoprotein vary from 6 KDA (Apo C1) to 550 KDA
(Apo B100)
 Apolipoprotein E is rich in Arginine
 Apo(a):Carbohydrate rich protein, covalently bind the
Apo B 100 through a disulfide bond
 Lipoprotein (a)[Lp(a)] particle contains one molecule of
Apo (a) and one molecule of Apo B 100
 Family Apolipoprote Density class of lipoproteins Synthesis
in
    1. HDL- most important 1. Liver
  Apo-AI 2. Chylomicrons 2. Intestine
 Apo-A Apo-AII HDL & chylomicrons
Apo-AIV HDL & chylomicrons Intestine
Apo-AV Chylomicrons, VLDL Liver
  Apo-B100 IDL, LDL, VLDL Liver
Apo-B Apo-B48 Chylomicrons Intestine
   Apo-CI 1. Chylomicron Liver
Apo-C Apo-CII 2. VLDL
Apo-CIII 3. HDL
 Apo-D --------  HDL Spleen, brain, testis,
adrenal
    1. Chylomicron  
Apo-E -------- 2. VLDL Liver
3. HDL
Important apolipoproteins associated with various lipoproteins are:

HDL Apo-AI → Major structural protein,

Apo-CII, Apo-E
LDL Apo-B100

VLDL Apo-B100, Apo-CII, Apo-E

Chylomicron Apo-B48, Apo-CII, Apo-E

 FUNCTIONS OF APOLIPOPROTEINS
I. Activating important enzymes in lipoprotein
metabolism pathway

II. Maintain the structural integrity of lipoprotein

complex

III. Facilitating the uptake of lipoprotein into cells

through their recognition by specific cell surface
receptors
 METABOLISM OF LIPOPROTEINS
A. Chylomicron:
 Chylomicrons carry dietary (exogenous) TAG, cholesterol, fat-
soluble vitamins, and cholesteryl esters to the peripheral tissues
 They are assembled in intestinal cells and secreted into lacteals of
lymphatic system and ultimately into blood
 Assembly of apolipoproteins and lipid into chylomicrons requires
microsomal triglyceride transfer protein ([MTP]
 Apo-B48 is a unique component of chylomicron
 Nascent chylomicron molecules only contain Apo-B48 and Apo-A
B. VLDL:
 Produced in the liver
 Carries endogenous TAG from the liver (site of synthesis) to the
peripheral tissues, where TAG is degraded by LPL
 VLDLs are secreted directly into the blood by the liver as nascent
particles containing Apo B-100
 They must obtain Apo C-II and Apo-E from circulating HDL
 As VLDLs pass through the circulation, TAG is degraded by LPL, causing
the VLDLs to decrease in size and become denser.
 C and E apolipoproteins, are returned to HDL, but VLDL particles retain Apo
B-100
 Additionally, some TAGs are transferred from VLDL to HDL in an exchange
reaction that concomitantly transfers cholesteryl esters from HDL to VLDL
by cholesteryl ester transfer protein (CETP)
 With these modifications, the VLDL is converted in the plasma to LDL
C. LDL:
 The primary function of LDL particles is to provide cholesterol to
the peripheral tissues or return it to the liver
 LDL transports cholesterol to various tissues by binding to cell surface
membrane LDL receptors ak/a Apo B-100/Apo E receptors
 After binding, the LDL–receptor complex is taken in by endocytosis
 The vesicle containing LDL loses its clathrin coat and fuses with other
similar vesicles, forming larger vesicles called endosomes
 The pH of the endosome falls (due to the proton-pumping activity of
endosomal ATPase), which allows separation of the LDL from its
receptor
 Lipoprotein remnants in the vesicle are transferred to lysosomes and
degraded by lysosomal acid hydrolases, releasing free cholesterol,
amino acids, fatty acids, and phospholipids
 D. HDL:
 Apo A-1 is made by the liver and intestine and secreted
into blood

 In bloodstream, addition of lipid to Apo-A1 gives rise to

HDL particles

 HDLs perform a number of important functions,

including the following

 Apolipoprotein supply: HDL particles serve as a

circulating reservoir of Apo C-II and Apo-E

 Reverse cholesterol transport

 APOLIPOPROTEIN-A
 Apo-A1 is:

1. Major structural protein of HDL

2. Major activator of and Cofactor for LCAT ( Lecithin Cholesterol Acyl

Transferase)

 To maintain the structural integrity of HDL the ratio of Apo AI: AII in HDL is
3:1
 Apo A-II: Inhibitor of LCAT and LPL
 Apo A-IV : activates LCAT in vitro
 Helps in transport of cholesterol from peripheral tissues to liver
 APOLIPOPROTEIN B

 Apo B100 and B48: The translation products of single structural gene

 Apo B100 :

1. Only structural protein in LDL

2. Helps in stabilization of chylomicrons

3. Major mediator of LDL uptake by LDL receptors of liver

 ApoB-48 is an exclusive content of chylomicrons

 APOLIPOPROTEIN-C

 Apo CI, CII, CIII associated with all lipoproteins except LDL

 Apo CI activates LCAT and LPL and inhibits CETP

 Apo CII is a principal activator of lipoprotein lipase(LPL) and

plays an important role in metabolism of TAG rich lipoprotein

 Apo CIII inhibits LPL & activates LCAT

 APO – E
 Present in chylomicron, VLDL, HDL & helps in metabolism of
chylomicrons and VLDL remnants
 It regulates & facilitates lipoprotein uptake in liver via:

I. Interaction of chylomicron remnants with chylomicron remnants

receptors
II. By binding of VLDL remnants to LDL receptors
Bad  LDL cholesterol
cholesterol  LDL transports both exogenous (dietary) & endogenous
cholesterol from liver to peripheral tissues
 It is the major source of cholesterol in peripheral tissues
 It is the causative agent of coronary artery disease (CAD),
atherosclerosis & AMI
 Therefore, a marker for cardiovascular disease
Good  HDL cholesterol
cholesterol  Helps in reverse cholesterol transport; i.e. transport of
cholesterol from peripheral tissues to liver for excretion
 Scavengers - remove free/ unesterified cholesterol from
extra-hepatic tissue; thereby preventing atherosclerosis
& AMI
 Hence, HDL is cardioprotective and anti-atherogenic
(particularly, HDL-2)
 SEPARATION OF LIPOPROTEINS
 Electrophoresis: Frederickson’s method
 Separation of LPs on basis of charge & mass; i.e. by their charge/
size ratio
 Different mobility towards the positively charged end/ anode on
paper/ agarose electrophoretic media

   
Chylomicron No mobility- remains in original position
 
LDL β-globulin region
   
VLDL Pre- β-globulin region
 
   
HDL α-globulin region
 
 DISORDERS OF LIPOPROTEIN METABOLISM
1. Hyperlipoproteinemias
2. Hypolipoproteinemias

Hyperlipoproteinemias: Fredrickson’s classification- 5 types.

Type-1 Familial LPL deficiency ↑TAG (Hypertriglyceridemia);

Pancreatitis
Type-2a Familial hypercholesterolemia ↑LDL
LDL receptor deficiency
Type-2b Familial combined hyperlipidemia ↑LDL, ↑VLDL
LDL receptor deficiency
↑ secretion of Apo-B100
Type-3 familial dysbetalipoproteinemia/ broad-β-disease ↑Cholesterol, ↑TAG,
Abnormality in Apo-E (E4) Xanthoma, atherosclerosis
Type-4 Familial hypertriglyceridemia ↑VLDL
↓Apo-A-V
Type-5 Endogenous hypertriglyceridemia ↑VLDL + TAG
Abetalipoproteinemia:
 Deficiency of Apo-B containing LPs
 Extremely low serum cholesterol
 Normal HDL level
 Malabsorption of TAG & lipid soluble vitamins
 Accumulation of Apo B in enterocytes & hepatocytes & lipid droplets
 PBS shows acanthocytes
 Neurological disease, Retinitis pigmentosa, Ataxia, Retardation

Tangier’s disease:
 Rare autosomal disorder
 α lipoprotein deficiency [ HDL-c (deficiency of Apo A1)]
 Severe decrease in plasma HDL
 Hepatosplenomegaly
 Orange tonsil
 Neuropathy
Familial LCAT Deficiency:
 Autosomal recessive disorder characterized by high level of LDL,
chylomicrons
 Due to mutation in LCAT enzyme, which synthesized in liver with the help
of Apo A1
 It has two types
 primary or complete deficiency (fish eye Disease)
 secondary-progressive renal failure

Alzheimer’s disease:
 Alzheimer’s disease has a correlation with Apo E4,
 People having the Apo E4 allele has a tendency to develop Alzheimer’s
disease
 Apo E2 & E3 helps in cytoskeletal configuration (microtubules) of neurons,
which is not a feature of Apo E4, thus it might affect the growth of amyloid
fibers
Thank You!!!!!