Chylomicrons and VLDL carry many apolipoproteins,
among them apo-B and apo-E. Apo-B is a large
(MW=516 kDa) protein stably associated with the
lipoprotein particle. The intestine produces a truncated
form of the apoB, termed apo
-B48, which is missing the
carboxy-terminal half of apoB. The mechanism for the
truncation involves a unique RNA editing event in the intestine
that changes a Gln codon (CAA) to a STOP codon
(UAA). Since only VLDL is converted to LDL, this means
all apo-B in LDL is apo-B100 (Fig. 7).
Main Features of VLDL and IDL Metabolism
- The liver is an important lipogenic tissue and exports
newly synthesized triglyceride in VLDL particles.
- VLDL is synthesized in the liver and secreted directly
into the bloodstream.
- As occurs with chylomicrons, VLDL is acted upon by
lipoprotein lipase, on the surface of adipose and
muscle capillaries. Unlike chylomicrons, VLDL
remnants (IDL) are both cleared from the circulation
and converted to LDL. This branch point is a factor
that determines the rate of LDL production.
Whether or not a particle carries apo-B48 or apo-B100
has physiological importance. The carboxy-terminal half
of apo-B is required for receptor recognition. Thus, apo-
B100 can bind to cellular receptors (described below);
apo-B48 cannot. For this reason, chylomicron remnants
cannot be cleared from the circulation via apo-B48. Instead,
chylomicron remnant clearance is mediated by another
receptor ligand, apo-E. Indeed, genetic deficiency of
apo-E leads to massive accumulation of cholesterol esterrich
chylomicron remnants and IDL in the bloodstream.
If chylomicrons and VLDL contain apo-E, why are they
not cleared before they are acted upon by lipoprotein lipase?
One explanation is that the apo-E on chylomicrons
and VLDL is masked by another protein, apoC-III. During
lipolysis, the apoC-III protein falls off the particle, thereby
exposing apo-E and permitting it to mediate particle
Some Key Points
In terms of mass movement, export of triglyceride
(TG) from the liver and intestine is where the action
is. This means net movement to extrahepatic cells.
- Most of the plasma TG (in the fasting state, when no
chylomicrons are present) is carried in VLDL. Thus,
if fasting plasma TG is high, VLDL is high.
- Dietary fat is packaged into chylomicrons in the
intestine. Excess endogenous substrate is converted
into TG for export by the liver.
- Chylomicrons and VLDL are depleted of TG in the
circulation, thus accomplishing their mission of
delivering TG to peripheral cells.
- Chylomicron remnants are not converted to LDL; they
are cleared by the liver.
- Only VLDL can be converted to LDL.
- In humans, most of the plasma cholesterol is carried in
LDL. If plasma cholesterol is elevated without
elevation of plasma TG, then LDL is high.