C h a p t e r 1 8
Disorders of Blood Flow and Blood Pressure
405
apoB-100) remain attached to the same lipoprotein par-
ticle from biosynthesis to breakdown.
8
There are two pathways involved in the generation
and transport of lipoproteins: the exogenous intesti-
nal and endogenous hepatic pathways.
1,2,7,9
The exog-
enous pathway is involved in the transport of dietary
cholesterol and triglycerides from the intestine to the
liver. The endogenous pathway involves the processing
of triglycerides and cholesterol by the liver and their
distribution throughout the body (Fig. 18-4).
Exogenous Pathway.
The exogenous pathway involves
the chylomicron transport of dietary triglycerides and
cholesterol from the intestines to the liver. The chylomi-
crons, which are the largest of the lipoprotein molecules,
are synthesized in the wall of the small intestine. These
triglyceride-rich lipoproteins transfer their triglycerides
to peripheral tissues, especially adipose tissue and skel-
etal muscle, for energy and storage. The remnant chy-
lomicron particles, which contain cholesterol, are then
taken up by the liver and the cholesterol is used in the
synthesis of VLDL or excreted in the bile.
Endogenous Pathway.
The liver is the central site for
handling of lipids: it is able to store glycerols and fats in
its cells; synthesize triglycerides; and use esterified cho-
lesterol and triglycerides to form VLDL. Like chylomi-
crons, VLDLs carry their triglycerides to fat and muscle
cells, where the triglycerides are removed. The resulting
IDL particles, which are reduced in triglyceride content
and enriched in cholesterol, are then taken to the liver
and recycled to form VLDL or converted to LDL.
Low-Density Lipoproteins
Sometimes called
bad cholesterol
, LDL is the main car-
rier of cholesterol. Low-density lipoprotein particles are
rich in cholesterol and cholesterol esters. Approximately
60% of the LDL is transported back to the liver, where its
apoB-100 binds to specific LDL receptors on liver cells,
allowing the particles to be internalized.
2,7,9
The remain-
ing 40% of LDL particles are carried to extrahepatic
tissues, such as those of the adrenal cortex and gonads,
which also have apoB-100 receptors that allow them to
internalize the LDL particles and use the cholesterol in the
synthesis of their cell membranes and steroid hormones.
There are different types of LDL, and some people
with markedly elevated LDL do not develop atheroscle-
rotic vascular disease, whereas other people with only
modest elevations in LDL develop severe disease. This
can be partially explained by the quality and size of the
LDL particles. Small, dense LDL is more toxic or ath-
erogenic to the endothelium than large, buoyant LDL. It
is more likely to enter the vessel wall, become oxidized,
and trigger the atherosclerotic process.
High-Density Lipoproteins
Often referred to as the
good cholesterol,
HDL is synthe-
sized by several pathways, including direct secretion by
the intestine and liver and transfer of lipid constituents
released during lipolysis of lipoproteins that contain apo-
B100. It participates in reverse cholesterol transport (see
Fig. 18-4)—that is, carrying cholesterol from the periph-
eral tissues back to the liver. Epidemiologic studies show
an inverse relation between HDL levels and the develop-
ment of atherosclerosis.
6
It is thought that HDL, which
is low in cholesterol and rich in surface phospholipids,
Low
density
High
density
HDL
5% triglycerides,
20% cholesterol,
50% protein
LDL
10% triglycerides,
50% cholesterol,
25% protein
Chylomicrons
80%–90% triglycerides,
2% protein
VLDL
55%–65% triglycerides,
10% cholesterol,
5%–10% protein
FIGURE 18-2.
Lipoproteins are named based on their protein
content, which is measured in density. Because fats are less
dense than proteins, as the proportion of triglycerides decreases,
the density increases. HDL, high-density lipoprotein; LDL,
low-density lipoprotein; VLDL, very–low-density lipoprotein.
Cholesterol
esters
Nonesterified
cholesterol
Phospholipids
Apolipoproteins
Triglycerides
FIGURE 18-3.
General structure of a lipoprotein.The
cholesterol esters and triglycerides are located in the
hydrophobic core of the macromolecule, surrounded by
an outer hydrophilic shell of phospholipids, nonesterified
lipoproteins, and apolipoproteins.
