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

426
Chapter | 14 Gastrointestinal Function
3 . Monosaccharide Transport
a . Specificity of Monosaccharide Transport
Regardless of whether monosaccharides originate in the
lumen of the intestine or are formed at the surface of the
mucosal cell, transport across the mucosa involves processes
that have a high degree of chemical specificity. Glucose and
galactose are absorbed from the intestine more rapidly than
other monosaccharides. Fructose is absorbed at approximately
half the rate of glucose, and mannose is absorbed at
less than one-tenth the rate of glucose ( Kohn et al., 1965 ).
Glucose and galactose can be absorbed against a concentration
gradient. The monosaccharides that are transported
most efficiently against gradients have common structural
characteristics: (1) the presence of a pyranose ring, (2) a
carbon atom attached to C-5, and (3) a hydroxyl group at
C-2 with the same stereoconfiguration as D-glucose, but
these features are not absolute requirements. Both D-xylose,
which has no substituted carbon atom at C-5, and D-mannose,
which lacks the appropriate hydroxyl configuration
at C-2, can be transported against concentration gradients
under specific experimental conditions ( Alvarado, 1966b ).
Glucose transport is competitively inhibited by galactose
( Fisher and Parsons, 1953 ) and by a variety of substituted
hexoses that compete with glucose for carrier
binding sites. The glucoside phlorizin is a potent inhibitor
( Alvarado and Crane, 1962 ; Parsons et al., 1958 ). Phlorizin
also competes for binding sites but has a much higher
affinity for these sites than does glucose.
The absorptive surface of the mucosal cell is the microvillous
membrane, or brush border. It is through this part
of the plasma membrane that glucose must pass during
the initial phase of mucosal transport. Techniques have
been developed for isolating highly purified preparations
of microvillous membranes from mucosal homogenates
( Forstner et al., 1968 ). Faust et al. (1967) studied the binding
of various sugars to these isolated membrane fractions.
They found that D-glucose was bound by the membrane
preferentially to L-glucose or to D-mannose and that glucose
binding was completely inhibited by 0.1 mM phlorizin.
The specificity of their observations suggested that
binding represented an initial step in glucose transport,
namely, attachment to a membrane carrier.
b . Sodium Requirement
The absorption of glucose and other monosaccharides is
influenced significantly by Na (Kimmich, 1973 ; Schultz
and Curran, 1970 ). When Na is present in the solution
bathing the intestinal mucosa, glucose is absorbed rapidly,
but when Na is removed and replaced by equimolar
amounts of other cations, glucose absorption virtually stops
( Bihler and Crane, 1962 ; Bihler et al., 1962 ; Csaky, 1961 ;
Riklis and Quastel, 1958 ). Glucose absorption is inhibited by
ouabain, digitalis, and other cardiac glycosides that are also
inhibitors of Na -K -ATPase activity and Na transport
FIGURE 14-5 Model of a Na
-activated glucose carrier of the intestinal
brush border. (From Wright and Peerce, 1985 ).
( Csaky and Hara, 1965 ; Schultz and Zalusky, 1964 ). These
observations demonstrate the close relationship between
the transport of glucose and Na .
c . Characteristics of the Na -Glucose Transporter
(Carrier)
The concentrative step in the active transport of glucose
occurs at the brush border membrane, and energy for this
process is derived from an electrochemical Na gradient
( Schultz, 1977 ; Schultz and Curran, 1970 ). Under conditions
of net influx, Na and glucose enter in a ratio of
1:1 ( Goldner et al., 1969 ; Hopfer and Groseclose, 1980 ).
Cotransport of glucose and Na involves a membrane
transporter or carrier that is believed to be a 75-kd polypeptide
( Wright and Peerce, 1985 ). Na activates glucose
transport primarily by increasing the affinity of the carrier
for glucose. A model showing two hypothetical forms of
the glucose carrier is presented in Figure 14-5 . A galent
channel or pore mechanism has been proposed in which
the glucose binding site is located within the membrane.
The translocation of glucose in this model is believed to be
the result of a Na -induced conformational change in the
transporter ( Semenza et al., 1984 ).
C . Proteins
1 . Enzymatic Hydrolysis
The initial step in protein digestion is the enzymatic
hydrolysis of peptide bonds by proteases with formation
of smaller peptides and amino acids. The endopeptidases
hydrolyze peptide bonds within the protein molecule and
also hydrolyze certain model peptides. Exopeptidases
hydrolyze either the carboxy-terminal (carboxypeptidase)
or the amino-terminal (aminopeptidase) amino acids of
peptides and certain proteins. Thus, a mixture of exopeptidases
and endopeptidases cleaves long chain polypeptides
from the ends as well as within the length of the chain
resulting in sequentially shorter and shorter polypeptide
chains and amino acids.
Dietary proteins first come in contact with proteolytic
enzymes in the stomach. The best known of the gastric
proteases is the family of pepsins ( Samloff, 1971 ), which