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

VII. Digestion and Absorption
431
Lumen
Mucosa
Serosa
Fatty acid
Fatty acid CoA ATP
Fatty acid-CoA
Glucose
L--glycerophosphate
Monoglyceride-P
Fatty acid-CoA
Glycerol
Diglyceride-P
Monoglyceride
Fatty acid-CoA
Diglyceride
Triglyceride
Fatty acid-CoA
Chylomicron
formation
Triglyceride in
chylomicrons
(lymphatics)
FIGURE 14-7 Biochemical reactions involved in intestinal transport of long chain fatty acids and monoglycerides.
From Isselbacher (1966) .
Within the mucosal cell, the fatty acids are transported
by a soluble binding protein to the endoplasmic reticulum,
where the fatty acids and monoglycerides are rapidly
reesterified to triglyceride ( Ockner and Isselbacher, 1974 ;
Ockner and Manning, 1974 ). The two biochemical pathways
for triglyceride biosynthesis in the intestine are summarized
in Figure 14-7 . Direct acylation of monoglyceride occurs in
the intestine and is the major pathway for lipogenesis in the
intestine during normal fat absorption. The initial step in this
series of reactions involves activation of fatty acids by acyl-
CoA synthetase, a reaction that requires Mg 2 , ATP, and
CoA and that has a marked specificity for long-chain fatty
acids. This specificity explains the observation by Bloom
et al. (1951) that medium- and short-chain fatty acids are
not incorporated into triglycerides during intestinal transport
but enter the portal circulation as nonesterified fatty acids.
The activated fatty acids then react sequentially with monoand
diglycerides to form triglycerides in steps catalyzed by
mono- and diglyceride transacylases. The enzymes responsible
for this series of reactions are present in the microsomal
fraction of the cell ( Rao and Johnston, 1966 ). These
enzymes occur together in the endoplasmic reticulum as a
“triglyceride-synthetase ” complex.
An alternate route that is available for fatty acid esterification
involves L- α -glycerophosphate derived either from
glucose or from dietary glycerol by the action of intestinal
glycerokinase. Activated fatty acid CoA derivatives
react with L- α -glycerophosphate to form lysophosphatidic
acid (monoglyceride phosphate), which by a second
acylation forms phosphatidic acid (diglyceride phosphate).
Phosphatidic acid phosphatase then hydrolyzes the phosphate
ester bond, forming diglyceride, and by means of a transacylase
step similar to that described previously, triglyceride
is formed. Although this pathway appears to be of minor
importance for triglyceride synthesis in the intestine, intermediates
in this sequence of reactions are important in the
synthesis of phospholipids, which are essential for stabilization
of the chylomicron.
The next step in fat transport is formation of chylomicrons
within the endoplasmic reticulum. The chylomicron
is composed primarily of triglyceride and has an outer
membranous coating of cholesterol, phospholipid, and
protein ( Zilversmit, 1965 ). The β -lipoprotein component
of the chylomicron is synthesized by the intestinal mucosal
cell. Inhibition of protein synthesis by puromycin or
acetoxycycloheximide interferes with chylomicron formation
and significantly reduces fat transport ( Sabesin and
Isselbacher, 1965 ).
The final step in fat absorption is extrusion of the chylomicra
into the intercellular space opposite the basal lateral
portion of the absorptive cell by reverse pinocytosis.
From the intercellular space, the chylomicra pass through
the basement membrane and enter the lacteal. The chylomicra
then pass from the lacteals into lymph ducts and into
the general circulation, thereby completely bypassing the
liver during the initial phase of absorption.
2 . Absorption of Other Lipids
a . Cholesterol
Dietary cholesterol is present in both free and esterified
forms, but only nonesterified cholesterol is absorbed.