Page 82 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN008C-380 June 29, 2001 16:42

Lipoprotein/Cholesterol Metabolism 649

FIGURE 6 The VLDL → IDL → LDL pathway. VLDL is secreted by the liver directly into the bloodstream. Like
chylomicrons, VLDL triglyceride is a substrate for lipoprotein lipase and is hydrolyzed while at the luminal surface
of adipose tissue and muscle capillaries. The VLDL remnant (IDL), unlike the chylomicron remnant, can give rise to
LDL. Some IDL is also directly cleared by the liver. LDL is cleared by the liver and by extrahepatic tissues.

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
FIGURE 7 Chylomicrons contain a different form of apoB than
has physiological importance. The carboxy-terminal half
VLDL or LDL. In the intestine, an RNA editing event introduces
a stop codon in apo-B, resulting in a truncated protein product, of apo-B is required for receptor recognition. Thus, apo-
apo-B48. VLDL is secreted with full-length apoB, apo-B100, and B100 can bind to cellular receptors (described below);
thus gives rise to LDL particles with apo-B100. The receptor- apo-B48 cannot. For this reason, chylomicron remnants
binding domain of apoB is at the C-terminal half of the protein, cannot be cleared from the circulation via apo-B48. In-
thus apo-B48 cannot bind to the LDL receptor; chylomicrons de- stead, chylomicron remnant clearance is mediated by an-
pend upon apo-E for receptor binding. Note: the particles are not
drawn to scale; chylomicrons are about five times larger than LDL other receptor ligand, apo-E. Indeed, genetic deficiency of
particles. apo-E leads to massive accumulation of cholesterol ester-
rich chylomicron remnants and IDL in the bloodstream.
If chylomicrons and VLDL contain apo-E, why are they
Main Features of VLDL and IDL Metabolism
not cleared before they are acted upon by lipoprotein li-
The liver is an important lipogenic tissue and exports pase? One explanation is that the apo-E on chylomicrons

newly synthesized triglyceride in VLDL particles. and VLDL is masked by another protein, apoC-III. During