Human Physiology, 14th edition (2016)

144 Chapter 6

glucose is transported against its concentration gradient by a

different kind of carrier, one that is dependent on simultaneous

transport of Na^1. Because this is a type of active transport, it

will be described shortly.

The transport of fatty acids through plasma membranes

has long been thought to occur by simple diffusion, due to the

hydrophobic nature of the fatty acids. However, more recent

evidence demonstrates that there are fatty acid transport car-

riers analogous to the GLUT carriers. These carrier proteins

facilitate the diffusion of fatty acids out of adipocytes and into

the blood, and out of the blood and into organs. Similar to glu-

cose transport by GLUT4, the uptake of fatty acids into skel-

etal muscle fibers by facilitative diffusion carriers is increased

by exercise and insulin.

Active Transport

Some aspects of cell transport cannot be explained by simple or

facilitated diffusion. The epithelial linings of the small intestine

and kidney tubules, for example, move glucose from the side of

lower to the side of higher concentration—from the space within

the tube ( lumen ) to the blood. Similarly, all cells extrude Ca^2 1

into the extracellular environment ( fig. 6.18 ) and, by this means,

maintain an intracellular Ca^2 1 concentration that is 1,000 to

10,000 times lower than the extracellular Ca^2 1 concentration.

Active transport is the movement of molecules and ions

against their concentration gradients, from lower to higher

concentrations. This transport requires the expenditure of cel-

lular energy obtained from ATP; if a cell is poisoned with cya-

nide (which inhibits oxidative phosphorylation; see chapter 5,

fig. 5.9), active transport will stop. Passive transport, by con-

trast, can continue even if metabolic poisons kill the cell by pre-

venting the formation of ATP. Because active transport involves

the transport of ions and molecules “uphill” (against their con-

centration gradients), and because it uses metabolic energy, the

primary active transport carriers are referred to as pumps.

Primary active transport occurs when the hydrolysis

of ATP is directly responsible for the function of the carriers,

which are proteins that span the thickness of the membrane.

Pumps of this type—including the Ca^2 1 pump ( fig. 6.18 ), the

and insulin. Because of this, GLUT4 is important for muscle
physiology (chapter 12) and for glucose homeostasis in health
and diabetes (chapter 19).
In unstimulated muscles, the GLUT4 proteins are located
within the membrane of cytoplasmic vesicles. Exercise—and
stimulation by insulin—causes these vesicles to fuse with
the plasma membrane. This process is similar to exocytosis
(chapter 3; also see fig.  6.23 ), except that no cellular prod-
uct is secreted. Instead, the transport carriers are inserted into
the plasma membrane ( fig. 6.17 ). During exercise and insulin
stimulation, therefore, more glucose is able to enter the skel-
etal muscle cells from the blood plasma.
Transport of glucose by GLUT carriers is a form of pas-
sive transport where glucose is always transported down its
concentration gradient. However, in certain cases (such as
the epithelial cells of the kidney tubules and small intestine),

Figure 6.17 The insertion of carrier proteins into
the plasma (cell) membrane. ( a ) In the unstimulated state,
carrier proteins (such as those for glucose) may be located in the
membrane of intracellular vesicles. ( b ) In response to stimulation,
the vesicle fuses with the plasma membrane and the carriers are
thereby inserted into the membrane.

(a)

(b)

Vesicle moves

when stimulated

Carriers are

intracellular

Plasma (cell)

membrane

Vesicle

Carrier

protein

Stimulated

by insulin

or exercise

Unstimulated

Carriers are inserted

into plasma (cell) membrane

CLINICAL APPLICATION

Hypoglycemia —an abnormally low plasma glucose

concentration—can produce a variety of symptoms caused

by the brain getting insufficient glucose. This results because

glucose transport from the blood plasma into tissue cells

occurs through facilitated diffusion. Although carrier proteins

mediate this transport, the rate of glucose entry into the tis-

sue cells depends on the concentration gradient, which is

reduced by hypoglycemia. Severe hypoglycemia, as may

occur in a diabetic person due to an overdose of insulin, can

result in the loss of consciousness or even death.