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

IV. Phospholipids
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The regulation of triacylglycerol synthesis is not fully
understood and differs among tissues. In small intestine,
substrate availability is most important because triacylglycerol
synthesis in that organ is an integral part of triacylglycerol
absorption. In mammary gland, substrate
availability and the hormones that support lactation regulate
triacylglycerol synthesis.
In liver, the limiting enzyme in the pathway appears to
be phosphatidate phosphohydrolase. This enzyme is subject
to an interesting control mechanism in which it is switched
between a less active and more active state by the enzyme
itself being translocated between the cytosol and endoplasmic
reticulum, respectively. Intracellular cAMP, which
increases with high plasma glucagon or low plasma insulin
levels (e.g., fasting or diabetes), inhibits binding of the
enzyme to the endoplasmic reticulum, whereas LCFA or
LCFA-CoA promote binding of the enzyme to the endoplasmic
reticulum ( Bernlohr et al ., 2002 ; Gurr et al ., 2002 ). The
role of LCFA and LCFA-CoA in promoting synthesis of triacylglycerols
in the liver is important and explains how fat
synthesis and fatty liver can occur in the fasting state when
hormonal changes would oppose triacylglycerol synthesis.
In adipose tissue, the synthesis of triacylglycerol is very
much regulated by hormones, especially glucagon, catecholamines,
and insulin. The first two hormones increase intracellular
cAMP, and the latter tends to decrease it, although
insulin probably has effects independent of cAMP. In conditions
in which glucagon would be elevated and insulin
would be decreased (e.g., fasting), hormone-sensitive lipase
will be activated and lipolysis will be occurring. It is important
that fat synthesis not be operative during lipolysis, so
as not to waste energy. Low insulin and elevated catecholamine
or glucagon levels decrease the level of lipoprotein
lipase (LPL) in adipose tissue. Fat cells need LPL in order
to hydrolyze plasma triacylglycerol so that the resulting
LCFA can be absorbed and used for triacylglycerol synthesis.
Decreased plasma insulin levels will decrease entry
of glucose into adipocytes, which will result in less glycerolphosphate
being synthesized. Increased intracellular
cAMP in adipose tissue decreases the activity of several
key enzymes in fat synthesis, including fatty acyl-CoA synthetase,
glycerolphosphate acyltransferase, phosphatidate
transferase, and diacylglycerol acyltransferase; however, the
mechanism of inhibition is uncertain ( Saggerson, 1988 ).
C. Catabolism of Triacylglycerol
Catabolism of triacylglycerol involves the action of lipases,
which are specialized esterases that hydrolyze glyceride
bonds. The major lipases are pancreatic lipase, hepatic
lipase, hormone-sensitive lipase of adipose, lipoprotein
lipase found on endothelial cells, and lysosomal lipases
contained in most cells. Pancreatic lipase is the essential
lipase for digestion of triacylglycerol in the GI tract and is
discussed later. Hepatic lipase is synthesized in hepatocytes
from where it migrates to the surface of hepatic endothelial
cells. Hepatic lipase primarily attacks triacylglycerol
in the plasma, which are part very low density lipoprotein
(VLDL) remnants to produce low-density lipoproteins
(LDL), and it attacks triacylglycerol in high-density lipoproteins
(HDL) as well.
Lipoprotein lipase attacks triacylglycerol in chylomicrons
and VLDL in plasma and is found on the endothelium
of many organs and tissues, but it is in greatest
quantity in adipose, heart, skeletal muscle, and mammary
gland. Lipoprotein lipase is synthesized by the underlying
tissue and migrates to the capillary endothelium where it
is anchored on the cell surfaces to glycoproteins, which
have polysaccharide chains structurally similar to heparin.
If heparin is injected into an animal, lipoprotein lipase can
switch its attachment from cell surface glycoproteins to the
free injected heparin and, thus, appears in the plasma. If
the animal had a lipemia before injecting the heparin, the
large amount of lipoprotein lipase released into the plasma
will clear the lipemia. Phospholipids and apolipoprotein
C-II must be present for lipoprotein lipase to have full
activity ( Fielding and Fielding, 2002 ).
IV. PHOSPHOLIPIDS
A. Structure and Properties of
Phospholipids
Most of the phospholipids found in the body consist of
a core of glycerol, which has LCFA esterified to its 1 and
2 carbons and phosphate esterified to its 3 carbon, a compound
called phosphatidate. In addition, the phosphate is
often esterified to a hydroxyamino compound such as choline,
ethanolamine, or serine to produce phosphatidylcholine
(also called lecithin), phosphatidylethanolamine, and phosphatidylserine,
respectively. Inositol may be esterified to the
phosphate to produce phosphatidylinositol. Because of the
phosphate group, phospholipids are very polar on one end
but are nonpolar on the other end and still must be part of
lipoproteins for transport through the plasma. Phospholipids
are constituents of all cellular membranes, lipoproteins, and
bile micelles. The fatty acid portion of the molecule is oriented
toward the center of the membrane or micelle, and
the phosphatidyl group is oriented toward the outer surface
(i.e., toward the aqueous medium). In micellar structures,
like lipoproteins and bile micelles, the surface coating of the
polar ends of constituent phospholipids provides a surface
charge that helps to keep the micelles in suspension.
B. Synthesis of Phospholipids
Phospholipids are synthesized either from phosphatidate
(e.g., phosphatidylinositol) or diacylglycerol (e.g., phosphatidylcholine
and phosphatidylethanolamine), both of