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

88
Chapter | 4 Lipids and Ketones
which are intermediates in the synthesis of triacylglycerol.
In all cases, cytidine triphosphate (CTP), a high-energy
organophosphate that derives its phosphates from ATP, plays
an important role. In the case of phosphatidylinositol, CTP
reacts with phosphatidate to form CDP-diacylglycerol,
which then reacts with inositol to form phosphatidylinositol
and CMP. In the case of choline or ethanolamine, it must
first be phosphorylated by reaction with ATP. Then the
phosphocholine or phosphoethanolamine reacts with CTP
to form CDP-choline or CDP-ethanolamine, respectively,
which then reacts with diacylglycerol to produce phosphatidylcholine
and phosphatidylethanolamine, respectively.
Phosphatidylserine is formed by serine replacing ethanolamine
in phosphatidylethanolamine. In the endoplasmic
reticulum of the liver, a methyl group from S-adenosylmethionine
can be transferred to phosphatidylethanolamine to
produce phosphatidylcholine ( Vance, 2002a ). Figure 4-3
illustrates the synthesis of phospholipids.
The enzymes that synthesize CDP-choline and CDPethanolamine
(cytidylyltransferases) appear to be rate
limiting for the synthesis of phosphatidylcholine and
phosphatidylethanolamine, respectively. Phosphocholine
cytidylyltransferase is subject to regulation similar to that
of phosphatidate phosphohydrolase, the control enzyme
in triacylglycerol synthesis. When phosphocholine cytidylyltransferase
is bound to the endoplasmic reticulum,
it is relatively active, but when it is free in the cytosol, it
is relatively inactive. Factors that increase binding of the
enzyme to the endoplasmic reticulum are decreased levels
of phosphatidylcholine, increased levels of diacylglycerol
or LCFA, and dephosphorylation of the enzyme. Opposite
changes in these factors inhibit binding of the enzyme to
the endoplasmic reticulum forcing it to remain inactive
( Vance, 2002a ).
C. Catabolism of Phospholipids
Phospholipids are hydrolyzed by phospholipases, which
can be found in lysosomes of most tissues and in pancreatic
secretion. Mammalian phospholipases are primarily of
the A type, meaning that they hydrolyze the glycerol-LCFA
ester bond at either position 1 (A 1 type) or 2 (A 2 type), but
not both ( Gurr et al ., 2002 ; Waite, 2002 ). Phospholipase
types B, C, and D, which hydrolyze at other locations in
the molecule, exist in mammalian tissues, but with lower
activities.
FIGURE 4-3 Synthesis of phospholipids. Diacylglycerol is the lipid to which organic bases and phosphate are
transferred via CDP derivatives. Abbreviations: CTP, CDP, CMP, cytidine tri-, di-, and mono-phosphate, respectively.