LIPID
TRANSPORT
• Fat from the diet and lipids synthesized
by the liver and adipose tissue must be
transported between the various
tissues and organs for utilization and
storage.
• lipids are insoluble in water.
• how to transport them in plasma?
• LIPOPROTEINS
• Surface: polar
• Core (centre): non polar
• nonpolar lipid core consists of TAG
and cholesteryl ester.
• Surface: of amphipathic phospholipid
and free cholesterol & proteins.
• The protein part is known as an
apolipoprotein or apoprotein,
• 1: chylomicrons: intestinal
• absorption of lipids.
• 2. very low density lipoproteins (VLDL)
from the liver
• 3. low-density lipoproteins (LDL)
• 4. high-density lipoproteins (HDL)
involved in VLDL and chylomicron
metabolism and cholesteroL transport.
• TAG: is the main lipid in chylomicrons
and VLDL.
cholesterol: main lipids in LDL
phospholipid: are the main lipids in
HDL.
• Apolipoproteins:
• The main apolipoprotein of HDL (α-
lipoprotein) is A
• The main apolipoprotein of LDL (β-
lipoprotein) is apolipoprotein B (B-100)
and is found also in VLDL.
• Chylomicrons apoB (B-48)
• B-48: synthesis(intestine)
• B-100 synthesis(liver)
• Apo C-I, C-II, and C-III
• are smaller polypeptides
• freely transferable between different
lipoproteins.
• Apo E is found in VLDL, HDL,
chylomicrons, and chylomicron
remnants;
• Funtions of Apolipoproteins:
• 1. form part of the structure of the
lipoprotein
• 2. enzyme cofactors, eg, C-II for
lipoprotein lipase
• 3. ligands for interaction with
lipoprotein receptors in tissues, eg, apo
B-100 and apo E for the LDL receptor.
• Transport of TAG:
• Chylomicrons:
• transport of all dietary lipids into the
circulation.(TAG)
• VLDL( hepatic) transport of TAG from
the liver to the extrahepatic tissues.
• Newly secreted or “nascent”
chylomicrons and VLDL contain only a
small amount of apolipoproteins C and
E, and the full complement is acquired
from HDL in the circulation
• Apo B is essential for chylomicron and
• VLDL formation.
• abetalipoproteinemia (a rare disease),
lipoproteins containing apo B are not
formed and lipid droplets accumulate in
the intestine and liver.
• Lipoprotein lipase:
• capillaries, heparan sulfate.
• heart, adipose tissue, spleen, lung,
renal medulla, aorta, diaphragm, and
lactating mammary gland, not active in
adult liver.
• Heparin.
• Both phospholipids and apo C-II are
required as cofactors for lipoprotein
lipase activity, while apo A-II and apo
C-III act as inhibitors.
• Hepatic lipase
• This enzyme is concerned with
chylomicron remnant and HDL
metabolism.
• The VLDL receptor
• delivery of fatty acids from VLDL
triacylglycerol to adipocytes by binding
VLDL and bringing it into close contact
with lipoprotein lipase.
• In adipose tissue, insulin enhances
lipoprotein lipase synthesis
• lipoprotein lipase
• Loss of 90% of TAG of chylomicrons
• loss of apo C (which returns to HDL)
• but not apo E, which is retained.
• resulting in chylomicron remnant
• Also VLDL, with the formation of VLDL
remnants or IDL
• Chylomicron remnants are taken up by
the liver by receptor- mediated
endocytosis, and the cholesteryl esters
• TAG are hydrolyzed and metabolized.
• Uptake is mediated by a recept specific
for apo E.
• Hepatic lipase:
• hydrolyzing its TAG and phospholipid.
• fates of IDL:
• taken up by the liver directly via the
LDL (apo B-100, E) receptor,
• or converted to LDL.
• In humans, a relatively large proportion
forms LDL.
• The liver and many tissues express
• LDL (B-100, E) receptor
• This receptor is defective in familial
hypercholesterolemia.
• 30% of LDL is degraded in extrahepatic
tissues and 70% in the liver.
• coronary atherosclerosis and the
plasma level of LDL cholesterol.
• HDL: synthesized and secreted from
both liver and intestine.
• apo C,apo E synthesized in the liver
transferred from liver HDL to intestinal
HDL in plasma.
• HDL act as a repository for the apo C
and apo E for metabolism of
chylomicronsand VLDL.
• Nascent HDL consists of discoid
• phospholipid bilayers containing apo A
and free cholesterol.
• lecithin:cholesterol acyltransferase
• (LCAT) bind to the disk, and the
surface phospholipid and free
cholesterol are converted into
cholesteryl esters
• The nonpolar cholesteryl esters move
into the hydrophobic interior of the
bilayer, whereas lysolecithin is
transferred to plasma albumin
• LCAT remove excess free cholesterol
from lipoproteins and tissues.
• transport of cholesterol from the
tissues to the liver is known as reverse
cholesterol transport and is mediated
by an HDL cycle
• The smaller HDL3 accepts cholesterol
from the tissues.
• cholesterol is then esterified by LCAT,
increasing the size of the particles to
form the less dense HDL2. The cycle is
completed by the re-formation of HDL3.
• free apo A-I is released by these
processes and forms pre-HDL
after associating with a minimum
amount of phospholipid and
cholesterol. Preβ-HDL is the most
potent form of HDL in inducing
cholesterol efflux from the tissues to
form discoidal HDL.