F IG U R E 2 0 -3
Steps involved in the metabolism of chylomicrons (the exogenous pathway
of lipid transport).
Catabolism of chylomicron remnants may be viewed as
the second step in the processing of chylomicrons. After
the loss of apo C-II and other C and A apoproteins, LPL no
longer acts upon the remnants, and they leave the capillary
surface. Chylomicron remnants are rapidly removed by
uptake into liver parenchymal cells via receptor-mediated
endocytosis. Apo E is important in this uptake process.
The chytomicron receptors in liver are distinct from the
B-E receptor that mediates uptake of LDL. The hepatic
receptor for chylomicrons binds with apo E, but not apo
B-48. Another receptor, known as the LDL receptor-
related protein (LRP), may also function in chylomicron
uptake. Chylomicron remnants are transported into the
lysosomal compartment where acid lipases and proteases
complete their degradation. In the liver, fatty acids so re-
leased are oxidized or are reconverted to triacylglycerol,
which is stored or secreted as VLDL. The cholesterol may
be used in membrane synthesis, stored as cholesteryl ester,
or excreted in the bile unchanged or as bile acids.
monoacylglycerol to fatty acids and glycerol ensues. The
released fatty acids cross the endothelium and enter the
underlying tissue cells, where they undergo reesterifica-
tion to form triacylglycerol for storage (adipocytes) or are
oxidized to provide energy (e.g., muscle). The earlier ac-
quisition of apo C-II by chylomicrons is important because
this apoprotein is an essential activator of LPL. Chylomi-
cron triacylglycerol has a half-life of about 5 minutes in the
circulation. LPL is most active after meals, when it is stim-
ulated by elevated levels of plasma insulin. A low-affinity
form (high
m) of LPL, found principally in adipose tis-
sue, is most active when triacylglycerol levels in plama are
high; it promotes lipid storage after meals. A high-affinity
Km )
form of LPL predominates in heart (and striated
muscle tissues) and is active when triacylglycerol levels
are low, as in the postabsorptive state. The high-affinity
enzyme thus hydrolyzes triacylglycerols into fatty acids
at sites where they will be required for energy production.
Mammary gland LPL is a high-affinity type that facilitates
uptake of fatty acids to promote milk-fat synthesis during
As the core triacylglycerols of a chylomicron are de-
pleted, often reducing its diameter by a factor of
or more,
the surface components are also modified. A substantial
portion of the phospholipids and of apo A and C is trans-
ferred to HDL. The C apoproteins thus cycle repeatedly
between newly produced chylomicrons and HDL. The
chylomicron remnant
is consequently rich in cholesteryl
esters and apo B-48 and E.
Very-Low-Density Lipoproteins
VLDLs are produced by the parenchymal cells of the liver
from lipid and apoprotein constituents in a way similar to
that of chylomicron formation in enterocytes. However,
while the triacylglycerol core of chylomicrons is derived
exclusively from absorbed dietary fatty acids and monoa-
cylglycerols, VLDL triacylglycerols derive from
1. Stored fat released from adipose tissue as fatty acids,
2. Conversion of carbohydrates to fatty acids in the liver,
3. Hydrolysis of lipoprotein triacylglycerols on capillary
endothelia and in the liver.
Although synthesis of apoprotein B-100 is necessary
for VLDL secretion, addition of carbohydrate moieties in
the Golgi apparatus does not appear to be required, since
blockage of this function by tunicamycin does not reduce
VLDL secretion.
The amount of VLDL secreted by the liver is extremely
variable and can be affected in a number of ways. A pri-
mary determinant of VLDL output is the flux of free fatty
acids entering the liver. The liver responds to an increase
in free fatty acids by synthesis of more and larger VLDLs.
If saturated fatty acids predominate in the formation of tri-
acylglycerol, the VLDL particles will be more numerous
but smaller than if polyunsaturated fatty acids predomi-
nate. This finding may be related to the reduction in plasma
cholesterol levels that results from elevating the proportion
of polyunsaturated fats in the diet. The surface-to-volume
ratio is smaller in the larger VLDLs. Since cholesterol
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