LIPOPROTEINS

• Major role is transport of water insoluble

lipids
• They also play an important role in cholesterol
and triglyceride metabolism
• They undergo a series of complex metabolic
processes where changes and exchanges
occur in and between various lipoproteins this
is referred to as the lipoprotein cascade
 CHYLOMICRONS

• Transport dietary fat and are synthesized by

and released from the intestinal epithelial cells
• Lipid content is derived predominantly from
the alimentary tract and is considered
exogenous
• Major lipid fraction is TG constituting
approximately 80 % by weight
• 1-2 % of the total particle is made of
apolipoproteins notably B-48 , A-I , A- II, A-IV
and C
• Chylomicrons do not enter portal venous
circulation but traverse the lymphatics into
the thoracic duct
• They directly enter the jugular vein and the
main systemic circulation
• While traversing the lymphatics they acquire
significant quantities of Apo C from HDL
• In the systemic circulation Chylomicrons are
hydrolyzed by Lipoprotein Lipase (LPL)
• The TG component is hydrolyzed to
monoglycerides, glycerol and FFAs
• Apo A-I , A-II and C are transferred to HDL
together with a small amount of lipid
• The remainder of the Chylomicron is known as
the remnant ( 30 – 80 nm) and is rich in
cholesterol esters
• The remnants are rapidly removed from
circulation ( < 10 min ) by the Apo E receptor
in the liver
• They are rapidly internalized by receptor-
mediated endocytosis and degraded in the
hepatic lysosomes
 VERY LOW DENSITY LIPOPROTEINS (VLDL)

• VLDL is synthesized and released from the liver

• It transports hepatic-synthesized TG and
cholesterol derived from dietary precursors such
as FFAs, glycerol and CHO
• Synthesis is stimulated by energy excess without
regard to calorie source
• Besides TG , VLDL contains about 10 % cholesterol
and functionally important apoproteins
• Apo C- II in VLDL is a cofactor of extra hepatic
LDL which removes TG from VLDL
• Lack of C-II leads to accumulation of
Chylomicrons and VLDL
• As VLDL is catabolised, Apo C is transferred to
HDL
• Apo C on HDL is transferred back to
Chylomicrons and VLDL to complete the cycle
• The half-life of VLDL in serum is 1-3 h
 INTERMEDIATE - DENSITY LIPOPROTEINS (IDLs)

• After VLDL hydrolysis by LPL, a short-lived IDL particle

which is partly depleted of TG is formed
• It contains equal amounts of TG and cholesterol and
its major apolipoproteins are B and E
• Apo E determines the continued catabolic process
(cascade) of IDL to LDL for hepatic uptake and
degradation
• Disease processes characterized by defective
catabolism of chylomicron remnants and IDL
metabolism stem from a defect in Apo E
 LOW DENSITY LIPOPROTEIN

• normally IDL is further delipidated by hepatic

LPL to form LDL
• LDL catabolism takes place in the liver and
peripheral tissues
 LDL interacts with high affinity receptor sites
located in the cell membrane (coated pits)
 Bound LDL is internalized by invagination of the
pits into the cell and pinched off as endocytic
vesicles
 Vesicles fuse with the intracellular lysosomes
and LDL moiety undergoes enzymatic
degradation
 Esterified cholesterol in LDL is hydrolyzed by
lysosomal cholesterol esterase and free
cholesterol (FC) enters cytoplasm
• Release of FC is responsible for 3 regulatory
processes assisting cholesterol homeostasis:
 A) Suppression of the rate limiting step
catalyzed by HMGCo reductase and of new
cholesterol synthesis
B) Activation of ACAT to esterify excess
cholesterol for intracellular storage as
cholesterol ester droplets
C) Modulation of the number of receptors
expressed on the membrane
• A non-specific pathway (bulk endocytosis)
occurs in scavenger cells or macrophages of
the reticuloendothelial system
 HIGH DENSITY LIPOPROTEINS (HDLS)

• Consists of a number of polydisperse and

heterogeneous particles varying in respect to size
and lipid content
• Three well defined HDL subgroups include:
- HDLᶜ
- HDL₂
- HDL₃
• Approximately 50 % of the HDL mass is protein, 30
% phospholipid and 20 % cholesterol
• The major apoproteins on HDL are Apo A-I and
Apo A-II in the ratio of 3:1 by weight
• Both the liver and the intestine synthesize HDL
• Nascent HDL consists of Apo A-I, A-II, lecithin
and FC
• The discoidal (nascent) HDL is transformed
into the spherical form by the action of the
enzyme LCAT
• HDL components may arise from Chylomicrons
and VLDL during their catabolism
• HDL appears to play an important role in
cholesterol efflux from the tissues, thereby
reducing the amount of cholesterol stored in
tissues
• From epidemiological studies there seems to
be an inverse relationship and development of
coronary disease