Lipoproteins and lipid transport.

Fat absorbed from the diet & fat synthesized by

the liver must be transported between the
various tissues& organs for utilization & storage.

Since lipids are insoluble in water, these are

transported in the form of lipoprotein
 Structure of a lipoprotein includes:
1] a core: of TGL and/or cholesteryl esters.
2] a coat: of PL, unesterified cholesterol
and
specific proteins (Apo lipoproteins).


ABCA1 = adenosine triphosphate-binding cassette-A1; A-I = apolipoprotein A-I; B =

apolipoprotein B; CE = cholesterol ester; CETP = cholesteryl ester transfer protein; FC =
free cholesterol; HDL = high-density lipoprotein; LCAT = lecithin cholesterol
acyltransferase; LDL = low-density lipoprotein; LDLR = low-density lipoprotein receptor;
SR-B1 = scavenger receptor B1; TG = triglycerides
 Reverse cholesterol transport
Reverse cholesterol transport (RCT) is defined as:
the efflux of cholesterol from extrahepatic tissue and its transport to the liver for
excretion via the intestines together with bile acids.
HDL plays a key role in the efflux of cholesterol from atherosclerotic lesions and its
transport to the liver.
 Reverse cholesterol transport and the role of HDL
The main HDL protein, (ApoA-I), is synthesized by the liver (70%) and intestine.
In bloodstream, it binds with phospholipids (act as a reservoir for cholesterol transport ).
ApoA-I "guides" nascent HDL (poor in lipids & rich in protein) to extrahepatic tissues, mainly to macrophages,
where it interacts with the ***ATP binding cassette transporter A-1 (ABCA-1) receptor, and
extracts cholesterol from them.
Back in the bloodstream, lecithin-cholesterol acyltransferase (LCAT) esterifies the cholesterol, and
mature HDL is formed. LCAT catalyzes the transfer of 2-acyl groups from lecithin to free cholesterol from
macrophagescholesterol esters and lysolecithin.
This can return to the liver:
A] mainly interact with the ***Scavenger receptor class-B type I (SR-BI) in the hepatocytes and "pour" the
cholesterol into the liver for subsequent biliary excretion,
or B] can exchange their esterified cholesterol for triglycerides with (LDL) and (VLDL) by ***CETP, that
can travel to the liver to eliminate the cholesterol (via the LDL receptor).
The overall effect of CETP on HDL consists in depleting it of cholesterol esters and providing triglycerides,
such that the size of the HDL particle is reduced.

LCAT
Reverse cholesterol transport (RCT) is defined as:
the efflux of cholesterol from extrahepatic tissue and its transport to the liver for
excretion via the intestines together with bile acids.
HDL plays a key role in the efflux of cholesterol from atherosclerotic lesions and its
transport to the liver.
ATP binding cassette transporter A-1 (ABCA-1) receptor
Scavenger receptor class-B type I (SR-BI)
Cholesterol ester transfer protein (CETP), LCAT, ACAT

ATP binding cassette transporter A-1 (ABCA-1)

 Maturation and Remodelling of HDL
The nascent HDL particles undergo an intravascular process of remodelling and
maturation by the action of several enzymes:
LCAT (lecithin-cholesterol acyltransferase): within the discoidal nascent HDL molecule,
LCAT catalyzes the transfer of 2-acyl groups from lecithin to free cholesterol from
macrophagescholesterol esters and lysolecithin. The cholesterol esters are more
hydrophobic than free cholesterol, and therefore they move to the core of the lipoprotein
particle, thus forming a mature HDL molecule, which is large and spherical.
Cholesterol ester transfer protein (CETP): CETP transfer cholesterol esters from HDL
particles to lipoproteins that contain apoprotein B (LDL, chylomicrons and VLDL) in
exchange for triglycerides. CETP transfers triglycerides from VLDL, chylomicrons and LDL
to HDL.
The end result is the migration of cholesterol esters back to LDL; the Reverse cholesterol
transport (RCT) cycle is completed with the re-uptake of cholesterol esters by the liver LDL
receptors.
The overall effect of CETP on HDL consists in depleting it of cholesterol esters and
providing triglycerides, such that the size of the HDL particle is reduced.
HDL synthesis and
function
ACS refers to a spectrum of clinical presentations ranging from STEMI
to NSTEMI or in UA.
chylomicron (largest; lowest in
density due to high lipid/protein
ratio; highest in triacylglycerols as
% of weight)
VLDL (2nd highest in
triacylglycerols as % of weight)
IDL (intermediate density
lipoprotein)
LDL (highest in cholesteryl esters
as % of weight)
HDL (highest in density due to
high protein/lipid ratio).
Lipoproteins:
 Apolipoproteins
Apo A1 - Found in HDL, chylomicrons.
Apo B - Found in LDL, VLDL (B100), Chylomicrons (B48).
Apo CII - Causes release of FA in Capillaries
Apo E - Facilitates uptake in liver
Roles and Functions of Apo lipoproteins