1987). The activities of the intestinal
saccharidases vary along the length of both
the intestine (Vonk and Western, 1984) and
the villus (Alpers, 1987). There are a
number of factors that affect enzyme
activity along the length of the villus. Cells
differentiate as they migrate from the crypt
to the villus tip and change their pattern of
proteins synthesized. Different enzymes
also have different half-lives on the brush
border. This is due primarily to pancreatic
proteases hydrolysing the glycoprotein
anchors of the disaccharidases and releas-
ing them into the lumen. In some species,
including swine, the activities of some
membrane saccharidases such as sucrase
and maltase are modified differentially, but
lactase activity is rather constant (Karasov
and Hume, 1997). The distinction between
luminal and membrane digestion becomes
blurred. Membrane enzymes are released
into the lumen by proteases and cell
sloughing; in contrast, pancreatic amylase
adheres, to some extent, to the enterocyte
membrane (Alpers, 1987).
In the scheme of digestion of dietary
carbohydrates, most of the absorbable
monosaccharides are generated on the
surface of the absorptive enterocytes.
Logically, this would enhance the
efficiency of absorption (Ugolev, 1968), but
this logic is questioned (Alpers, 1987).
Glucose is the major monosaccharide avail-
able for absorption from most practical
diets. It is believed that glucose is absorbed
by both transcellular and paracellular
routes. The paracellular route, however, is
dependent on the transcellular route.
The major transcellular route is
the Na+-dependent co-transport system
(SGLT1). There are several reviews on the
mechanism of SGLT1 (Semenza et al.,
1984; Hopfer, 1987; Baly and Horuk, 1988;
Widdas, 1988; Wright, 1993). Na+is the
primary solute transported. Glucose is a co-
solute. In the absence of Na+, glucose
cannot be transported. Under in vitro
conditions, other cations may substitute for
Na+ although less effectively, but Na+ is
virtually the sole binding cation in vivo.
The preponderance of data suggest a single
SGLT1 in the intestine with a 2:1
Na+:glucose stoichiometric ratio. There is
some support, however, for two Na+-
dependent transporters in the intestine
with different affinities for glucose and 1:1
and 2:1 or even 3:1 Na+:glucose stoichio-
metric ratios, more similar to renal
proximal tubule glucose transporters.
Apical membrane events of the SGLT1
transport system appear to follow an
ordered mechanism. The first Na+binds to
a luminal portion of the SGLT1 protein
referred to as the gate. The gate has a
valence of 1 or 2. Binding of the first
Na+causes the gate to extend and expose
the binding site for glucose to the luminal
contents. Binding of Na+also decreases the
Kmfor glucose. Glucose binds, followed by
binding of a second Na+, causing the gate
to be neutralized or changed to a positive
charge. The gate snaps back, translocating
the binding sites to the cytosolic surface of
the enterocyte. The intracellular concentra-
tion of Na+is much lower than the extra-
cellular concentration and therefore Na+
dissociates from SGLT1. Dissociation of
Na+increases the Kmfor glucose and the
glucose dissociates. The second Na+
dissociates, returning a negative valence to
the ‘gate’. The electrical gradient of the cell
membrane (inside negative) slowly returns
the ‘gate’ of SGLT1 to the luminal surface.
Return of protein with empty binding sites
from the interior to the exterior of the
apical membrane is the rate-limiting step.
The affinity of SGLT1 for Na+ is
dependent on the electrical potential of the
membrane. At 0 and 150 mV, the Kmfor
Na+ is 50 and 5 mM Na+, respectively.
Under physiological conditions, the elec-
trical potential is estimated to be approxi-
mately 120 mV. Luminal, intracellular and
extracellular concentrations of Na+typic-
ally are 150, 10 and 150 mMNa+, respec-
tively (Guyton, 1971; Ferraris et al., 1990).
Likewise, the affinity of SGLT1 for glucose
is dependent on Na+concentration. At 2
and 100 mMNa+, the Kmfor glucose is >10
and <0.1 mM glucose, respectively. The
luminal and intracellular concentrations of
glucose vary and are difficult to measure.
Both increase during the absorptive state.
The intracellular concentration increasesGlucose Availability and Associated Metabolism 127