2 1 2
chapter 12
Gastrointestinal Digestion and Absorption
(Chapter 13), which is transported via the portal blood
system to the liver, where it is reconverted to glucose (glu-
coneogenesis, Chapter 15). The quantitative significance
of this mode of glucose transport is probably minimal.
Fructose transport is distinct from glucose-galactose
transport and requires a specific saturable membrane car-
rier (facilitated diffusion).
Na+-driven uptake of glucose and amino acids (see be-
low), is responsible for maintaining high intracellular con-
centrations of K+ and low concentrations of Na+ (the re-
verse of the relative concentrations of these ions in the
extracellular fluid). The Na+ and K+ gradient across the
cell membrane is involved in the maintenance of osmotic
equilibrium, propagation of nerve impulses, reabsorption
of solutes by the kidney, and other processes that require
the electrochemical energy of the ion gradients. Thus,
Na+,K+-ATPase plays a critical role in many important
functions of the body.
Na+,K+-ATPase is a transmembrane protein found al-
most exclusively in the plasma membrane. It has two ma-
jor subunits:
(M.W. ~ 95,000) and
(M.W. ~ 55,000).
The latter is a glycoprotein and is exposed to the exte-
rior of the cell. The former spans the entire membrane
(Figure 12-10). Minimum subunit stoichiometry required
for the activity of the enzyme is
and the most probable
native enzyme structure is (
The enzyme is asymmet-
F I G U R E 1 2 -1 0
Schematic representation of Na+, K+ -ATPase. The minimum subunit
stoichiometry of the active enzyme is
a fi,
and the native enzyme most
likely has (а/3)г structure. The enzyme spans the plasma membrane, with
the smaller
glycoprotein subunits projecting outside the cell. Each
functional unit has binding sites on both sides of the membrane; the outer
surface has K+ and cardiac glycoside binding sites, and the inner surface
has Na+ and ATP binding sites. [Reproduced with permission from
K. J. Sweadner and S. M. Goldin, Active transport of sodium and
potassium ions.
N. Engl. J. M ed.
rically oriented and drives active transport only in one di-
rection. The ATP binding site is located on the cytoplasmic
aspect of the a-subunit.
a cardiac glycoside (sim-
ilar to digitalis glycosides), which inhibits the enzyme,
also binds to the a-subunit but at a site that projects to the
exterior of the cell. The inhibition of Na+, K+-ATPase
activity indirectly leads to an increase in intracellular
Ca2+ concentration, which stimulates contraction in mus-
cle cells (Chapter 21), thus accounting for the therapeu-
tic effect of cardiac glycosides on the heart. Na+,K+-
ATPase requires the presence of Na+, K+, Mg2+, and
ATP. Each cycle of enzyme activity results in the ex-
trusion of three Na+ coupled to the transport of two K+
into the cell, with the hydrolysis of one molecule of ATP.
Thus, the enzyme utilizes the energy derived from ATP
hydrolysis to transport K+ into the cell and Na+ out of
the cell, against concentration gradients. Since unequal
numbers of monovalent cations are transferred across the
plasma membrane, a transmembrane electric current is
A model for the mechanism of action of the enzyme is
shown in Figure 12-11. It proposes that Na+,K+-ATPase
can exist in two (or more) conformational states: one bind-
ing Na+ or ATP (or both) and the other binding K+ or phos-
phate (or both). On the cytoplasmic side, Na+ binding ini-
tiates transient phosphorylation of an aspartate residue at
the active site, resulting in a cyclic process with transloca-
tion of Na+ from inside to outside and of K+ from outside
to inside. The vectorial equation for the transport is
3Na+ + 2K+ + ATP4" + H20 -»•
3 Na+ + 2K+ + ADP3" + HP02+ + H+
where i = inside and o = outside. Thyroid hormone in-
creases Na+,K+-ATPase activity (Chapter 33). Other AT-
Pases participate in the transport of other ions (e.g.,
K+,H+-ATPase, above; Ca
+-ATPase, Chapter 21).
Disorders o f Carbohydrate Digestion and Absorption
Carbohydrate malabsorption can occur in a number
of diseases that cause mucosal damage or dysfunction
(e.g., gastroenteritis, protein deficiency, gluten-sensitive
enteropathy). Disorders due to deficiencies of specific
oligosaccharidases are discussed below.
Lactose Intolerance (Milk Intolerance)
Lactose in-
tolerance is the most common disorder of carbohydrate
absorption. Lactase deficiency occurs in the majority of
human adults throughout the world and appears to be ge-
netically determined. The prevalence is high in persons
of African and Asian ancestry (> 65%) and low in per-
sons of Northern European ancestry. Lactase deficiency
in which mucosal lactase levels are low or absent at birth
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