Very Low Density Lipoproteins (VLDL)
High Density Lipoproteins (HDL)
Lipoprotein Structure
Protein part: Apoproteins (may be structural or transferred) or apolipoproteins
Lipid part:
 Each lipoprotein contains different types of lipids in various combinations
 Type of lipids in a lipoprotein is governed according to the type of lipoprotein
Spherical molecules of lipids and proteins (apoproteins) = amphipathic molecules
 Outer coat:
 Proteins: Apoproteins
 Lipids (amphipathic): Phospholipids (PL) &Free Cholesterol
 Inner core: Lipids (hydrophobic): Triglycerides (TG) & Cholesterol ester (CE)
Apolipoproteins (Apoproteins):
Five major classes (A-E) divided by structure & function, each has subclasses as Apo A, Apo CII
Functions:
Structural proteins ♥ Enzyme activators ♥ Recognition sites for cell-surface receptors
Types of Lipoproteins: different in lipid & protein composition & therefore, they differ in:
Size ♥ density ♥ Electrophoretic mobility
Plasma Lipoproteins
For triacylglycerol transport (TG-rich):
- Chylomicrons: TG of dietary origin
- VLDL:
TG of endogenous (hepatic) synthesis
For cholesterol transport (cholesterol-rich):
- LDL: Mainly free cholesterol
- HDL: Mainly esterified cholesterol
Chylomicrons
Synthesis: in intestinal mucosal cells
Function: Transport dietary lipids from GIT to tissues (& liver).
Responsible for physiological milky appearance of plasma (up to 2 hours after meal)
Structure: Lowest density ♥ largest size ♥ highest lipid % ♥ lowest protein % ♥ highest
triacylglycerol (dietary origin)
Lipoprotein Lipase
♥ Extracellular enzyme anchored by heparan sulphate to the capillary walls of most tissue
especially those of adipose tissue, cardiac & skeletal muscles
BUT Adult liver does not have this enzyme
♥ its synthesis & transfer to luminal surface of the capillary is stimulated by insulin (in fed state)
♥ Activated by apoC-II
Function of lipoprotein lipase
♥ hydrolyses circulating TG in chylomicrons to fatty acids & glycerol
♥ Fatty acids are stored (in adipose) or used for energy (in muscles)
♥ Glycerol is transferred to the liver (to be used for glycolysis, gluconeogenesis or lipid synthesis)
Deficiency of lipoprotein lipase (or apo CII):
♥ causes type 1 hyperlipoproteinemia (familial lipoprotein lipase deficiency)
♥ accumulation of chylomicrons in plasma (hypertriglyceridemia)
Lipoproteins
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Synthesis: in the liver
Structure: composed predominantly of triglycerides
(TG)
Function:
To carry lipids (mainly TG) from the liver to tissues.
In peripheral tissues, TG are degraded by
lipoprotein lipase to FA & glycerol.
Fatty liver (hepatic steatosis)
Occurs when TG synthesis in liver is more than
VLDL secretion
As in cases of:
Obesity
Uncontrolled DM
Chronic ethanol ingestion
Low Density Lipoproteins (LDL)
LDL is produced in the circulation as the end
product of VLDLs
Compared to VLDLs:
It contains only apo B-10
Smaller size & more dense (less lipids)
Lipid contents:
Less triglycerides (TG)
More cholesterol (C) & cholesterol ester (CE)
Function of LDL
Transport cholesterol from liver to peripheral tissues
Uptake at tissue level by LDL receptor-mediated
endocytosis recognized by apo B-100
Receptor-Mediated Endocytosis
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Synthesis: by intestine and liver
Nascent HDL:
Disk-shaped
Contains apo A-I, C-II and E
Contains primarily phospholipid (PC)
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Mature HDL (HDL2):
First, the HDL3 collects cholesterol (C) from peripheral
tissues & other lipoproteins.
Then, Cholesterol is converted to CE (by PCAT) to form
HDL2.
CE is transported to liver by HDL2.
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Composition of LDL and HDL
Low density lipoprotein (LDL)
Mostly free cholesterol
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High density lipoprotein (HDL)
Mostly cholesterol ester
More % protein
More % phospholipids
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Functions of HDL
Reservoir of apoproteins
e.g. Apo C-II and E to VLDL
Uptake of cholesterol: From peripheral tissue (& other
lipoproteins)
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Esterification of cholesterol:
 Enzyme: PCAT/LCAT
 Activator: Apo A-I
 Substrate: Cholesterol, Co-substrate: PC
 Product: Cholesterol ester (& Lyso-PC)
 Reverse cholesterol transport
 Transports cholesterol from peripheral tissues to liver
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Why Is HDL a Good Cholesterol carrier?
 Inverse relation between plasma HDL levels and
atherosclerosis
 Reverse cholesterol transport involves:
Efflux of cholesterol from peripheral tissues and other
lipoproteins to HDL3
 Esterification of cholesterol & binding of HDL2 to liver
(and steroidogenic cells) by scavenger receptor class B
(SR-B1)
 Selective transfer of cholesterol ester into these cells
 Release of lipid-depleted HDL3
LDL Receptor-Mediated Endocytosis: Regulation
Low Density Lipoprotein Cholesterol (LDL-C)
LDL-C = Total cholesterol – [HDL-C + TG/2.2 ] in
case of mmol/L or 5 in case of mg/dL
Lipoproteins
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Tasneem Aldraye
Lipoproteins
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Tasneem Aldraye
Lp (a):
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Simulates LDL but apo(a) covalently linked to apo B-100
Competes with plasminogen to plasminogen activator
Genetical element
Estrogen decreases it while trans fats increases it
Lipoproteins and Related Clinical Problems
 Atherosclerosis
 Hypertension
 Coronary heart diseases
 Lipoproteinemias (hypo- and hyper-)
 Fatty liver
Abnormalities in lipoprotein metabolism
Hyperlipoprotenemias
Type I hyperlipoproteinemia:
Type II hyperlipoproteinemia :
Familial lipoprotein lipase deficiency
Familial hypercholesterolemia
 Due deficiency of lipoprotein lipase or apo C-II
 Due to deficiency of functional LDL receptors
 Slow clearance of TG–rich lipoproteins in plasma
 Reduced clearance of LDL
(chylomicrons & VLDL)
 Elevation of plasma cholesterol (plasma TG remains
 Hypertriacylglyceremia (increased TG in blood)
normal)
 Treated by reducing fat in diet
 Predispose to atherosclerosis & CHD
Type III hyperlipoproteinemia
Type IV hyperlipoproteinemia
Familial dysbetalipoproteinemia
Familial hypertriacylglycerolemia
or broad B disease
 Increased production of VLDL
 Due to abnormal apo E (on chylomicrons)
 Commonly associated with type II DM & obesity
 Reduction of clearance of chylomicron remnants by
 Elevated blood TG & cholesterol
liver
 Predispose to atherosclerosis & CHD.
 Accumulation of chylomicron remnants in plasma.
 Hyperchloesterolemia
 Predispose to atherosclerosis & CHD
Hypolipoproteinemia
Abetalipoproteinemia
Familial hypobetalipoproteinanemia
 ↓ apo B-100 synthesis
 Defect in triacylglycerol transfer protein (MTP)
responsible for loading of apo-100 with lipids with no
 ↓ VLDL  ↓ blood TG & ↑ TG in liver
chylomicrons & no VLDL synthesis
 ↓ LDL  ↓ blood cholesterol
 No chylomicrons synthesis in intestine  ↓ blood TG
 No VLDL synthesis in liver  ↑ TG in liver
 No VLDL synthesis  no LDL  ↓ blood cholesterol
Lipoproteins
4
Tasneem Aldraye