Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 4 Lipids and Ketones
triacylglycerol. Its main apolipoproteins are B 100 , C-series,
and E, but some A-series is present as well. The A-series
apolipoproteins, which are synthesized in the small intestine,
transfer from HDL to VLDL soon after its secretion.
Some C-series and E apolipoprotein may transfer from
HDL to newly secreted VLDL as well. Like chylomicrons,
the main lipid component of VLDL is triacylglycerol (see
Table 4-1 ). VLDL and chylomicrons both serve as a means
to distribute triacylglycerol to tissues. In the case of chylomicrons,
the triacylglycerol is a product of fat digestion,
whereas in the case of VLDL, the triacylglycerol is synthesized
in the liver.
The assembly process for VLDL is complex ( Fig. 4-7 ).
Final steps in the synthesis of triacylglycerol, phospholipid,
and cholesterol occur in the smooth endoplasmic
reticulum. Microdroplets containing these three lipids and
cholesterol esters move toward the confluence of the rough
and smooth endoplasmic reticulums where they are joined
by apolipoproteins synthesized on the rough endoplasmic
reticulum to form the nascent VLDL.
The nascent VLDL particles move through microtubular
membranes to the Golgi apparatus where the apolipoproteins
are glycosylated. In the Golgi apparatus, the
nascent VLDL particles reach final composition and are
surrounded by membranes to form secretory granules.
The secretory granules merge with the plasma membrane
and spill their contents into the plasma (Alexander, 1976;
Vance, 2002b ).
The capacity of the liver to synthesize the protein components
of VLDL is stimulated by a diet high in carbohydrate.
It has been hypothesized that this stimulation is
due to increased insulin and decreased glucagon levels in
plasma. Most studies have shown that glucagon partially
inhibits hepatic VLDL secretion, whereas insulin stimulates
it ( Gibbons, 1990 ). Estrogens ( Crook and Seed, 1990 ;
Haffner and Valdez, 1995 ; Sacks and Walsh, 1994 ) and
glucocorticoids ( Gibbons, 1990 ; Martin-Sanz et al ., 1990 )
stimulate VLDL secretion.
The inherent capacity of the liver to synthesize the lipid
components exceeds its inherent capacity to synthesize the
protein components, a fundamental factor in the development
of fatty liver. In addition, phosphatidylcholine is
essential for lipoprotein assembly, so animals having a
deficiency of choline tend to develop fatty livers ( Vance,
2002a, 2002b ).
Triacylglycerol in plasma VLDL is hydrolyzed by lipoprotein
lipase just like triacylglycerol of chylomicrons, and
most of the released LCFA is absorbed by the underlying
tissue cells. As the VLDL shrink, some of the apolipoproteins
(C-series and E) transfer to HDL. Finally, the shrinking
VLDL becomes an IDL and then an LDL. The LDL will
attach to an apoprotein B 100 or E receptor on hepatocytes
or extrahepatic tissues and be taken into the cell where its
component parts will be hydrolyzed. The transport and
metabolism of VLDL are illustrated in Figure 4-8 .
FIGURE 4-7 Synthesis of very low density lipoprotein (VLDL) in liver.
Triacylglycerol and phospholipid synthesis occurs in the smooth endoplasmic
reticulum to generate lipid particles (large dots), which acquire
small amounts of cholesterol and its esters as well. Apolipoproteins (small
dots) are synthesized on the rough endoplasmic reticulum. Lipid particles
acquire apolipoproteins at the convergence of the rough and smooth endoplasmic
reticulum or by merging of sections of the two organelles. The
nascent VLDL move through tubular membranes to the Golgi apparatus
where apolipoproteins are glycosylated, and the nascent VLDL are collected
in secretory vesicles. The secretory vesicles migrate to and merge
with the plasma membrane (PM) and spill VLDL into the space of Dissé
(SD). The VLDL migrate through the fenestrae (F) between endothelial
cells (E) to enter the plasma in hepatic sinusoids.
E. Metabolism of High-Density Lipoproteins
HDL is synthesized by both liver and small intestine.
Nascent HDL produced in the small intestine has only
A-series apolipoproteins and gains C-series and E apolipoproteins
and LCAT, which are synthesized in the liver,
from other lipoproteins after it enters the circulation.
Nascent HDL produced in the liver gains its A-series apolipoprotein,
which is synthesized in the small intestine,
from other lipoproteins after it enters the circulation. HDL
serves two main functions. It is a repository for A-series,
C-series, and E apolipoproteins, and it transports cholesterol
from peripheral tissues to liver. LCAT is important
in this latter function. The conversion of cholesterol-tocholesterol
ester within HDL creates a favorable concentration
gradient from tissue cell to HDL, which promotes
migration of cholesterol from tissue cells to HDL ( Fielding
and Fielding, 2002 ; Gurr et al ., 2002 ).