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

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Chapter | 14 Gastrointestinal Function
Cholesterol esters are hydrolyzed within the lumen of the
intestine by sterol esterases secreted by the pancreas. Bile
salts are required both for the action of this enzyme and for
the absorption of nonesterified cholesterol. In the mucosal
cell, cholesterol is reesterified and transferred by way of
the lymph to the general circulation. The type of triglyceride
present in the diet significantly affects the absorption
of cholesterol and its distribution in lymph lipids ( Ockner
et al., 1969 ).
b . Vitamin A
The diet contains vitamin A activity in two principal forms:
(1) as esters of preformed vitamin A alcohol (retinol) and
fatty acids and (2) as provitamin A, primarily β -carotene.
Vitamin A ester is hydrolyzed by a pancreatic esterase
within the lumen ( Murthy and Ganguly, 1962 ), and
the free alcohol is absorbed in the upper small intestine.
Vitamin A alcohol is reesterified in the mucosa primarily
with palmitic acid. The vitamin A ester is absorbed by way
of the lymph, and after reaching the general circulation, it
is rapidly cleared from the plasma and stored in the liver.
In the postabsorptive state, vitamin A circulates as the free
alcohol, the form released as needed from the liver by the
action of hepatic retinylpalmitase esterase. The blood level
of vitamin A is independent of liver reserves, and, as long
as a small amount of vitamin A is present in the liver, the
blood level remains normal ( Dowling and Wald, 1958 ).
In diets that lack animal fat, the carotenes, primarily
β -carotene, serve as the major precursor of vitamin A. The
intestinal mucosa has a primary role in conversion of provitamin
A to the active vitamin, although conversion can
occur to a limited degree in other tissues. The mechanism
involves central cleavage of β -carotene into two active
vitamin A alcohol molecules that are subsequently esterified
and absorbed by the lymphatics as with preformed
vitamin A.
Bile salts are required for the mucosal uptake of
β -carotene and for the conversion of β -carotene to vitamin
A. Uptake of carotene and release of vitamin A ester
into the lymph are rate-limiting steps. Cattle absorb substantial
amounts of β -carotene without prior conversion to
vitamin A, and these pigments are responsible for much of
the yellow color of the plasma. Most other species have no
β -carotene in the plasma, and extraintestinal conversion is
thought to be more efficient in these species than in cattle
( Ganguly and Murthy, 1967 ).
c . Vitamin D
Vitamin D, like cholesterol, is a sterol that is absorbed
by the intestine and transported via the lymph ( Schachter
et al., 1964 ). Intestinal absorption differs, however, in that
vitamin D is transported to the lymph in nonesterified form.
The uptake of vitamin D by the mucosal cell is favored
by the presence of bile salts. Simultaneous absorption
of fat from micellar solutions increases transport of vitamin
D out of the cell into the lymph, the limiting step.
One of the major actions of vitamin D is to enhance the
intestinal absorption of calcium. Wasserman and coworkers
(1968) ( Wasserman and Taylor, 1966, 1968 ) have described
the mechanism of action of vitamin D. They have shown
that vitamin D causes synthesis of a calcium-binding protein
that plays a central role in the transport of calcium.
E . Cobalamin
Following ingestion, cobalamin is released from food in the
stomach ( Batt and Morgan, 1982 ; Simpson et al., 2001 ). It
is then bound to a nonspecific cobalamin-binding protein
of salivary and gastric origin called haptocorrin. Intrinsic
factor (IF), a cobalamin-binding protein that promotes
cobalamin absorption in the ileum, is produced by parietal
cells and cells at the base of antral glands in the dog but not
the cat; IF is produced in the pancreas of cats. The affinity
of cobalamin for haptocorrin is higher at acid pH than for
IF, so most is bound to haptocorrin in the stomach. Upon
entering the duodenum, haptocorrin is degraded by pancreatic
proteases, and cobalamin is transferred from haptocorrin
to IF, a process facilitated by the high affinity of IF for
cobalamin at neutral pH. Cobalamin-IF complexes traverse
the intestine until they bind to specific receptors (previously
called IFCR, but recently dubbed cubilin) located in
the microvillous pits of the apical brush border membrane
of ileal enterocytes. Cobalamin is then transcytosed to the
portal bloodstream and binds to a protein called transcobalamin
2(TC II), which mediates cobalamin absorption
by target cells. A portion of cobalamin taken up by hepatocytes
is rapidly (within an hour in the dog) reexcreted in
bile bound to haptocorrin. Cobalamin of hepatobiliary origin,
in common with dietary derived cobalamin, undergoes
transfer to IF and receptor mediated absorption, thus establishing
enterohepatic recirculation of the vitamin.
Low serum cobalamin concentrations in dogs have been
associated with exocrine pancreatic insufficiency (EPI),
severe intestinal disease, IF-Cbl receptor abnormalities,
and conditions associated with the proliferation of enteric
bacteria (e.g., stagnant loops). Cobalamin deficiency in
cats and dogs results in a significant metabolic disorder,
which can be ameliorated by treatment or correction of the
underlying cause.
Dietary folate polyglutamate is deconjugated by folate
deconjugase to folate monoglutamate, which is absorbed
by specific carriers in the proximal small intestine. Folate
deconjugase is a jejunal brush border enzyme. Folic acid,
which is produced by microorganisms in the small intestine,
is also absorbed and can increase existing serum
levels of folate. Serum levels of folate are expected to
decrease when the absorptive capacity of the proximal
intestine is severely compromised, as might occur with
infiltrative bowel disease.