Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

TRANSPORTERS AND ACTIVE MEMBRANE TRANSPORT
601
lipid
bilayer
solute
OUTWARD-
OPEN
OCCLUDED
INWARD-
OPEN
OUTSIDE
INSIDE
concentration
gradient
conformational changes that alternately expose the solute-binding site first on
one side of the membrane and then on the other—but never on both sides at the
same time. The transition occurs through an intermediate state in which the solute
is inaccessible, or occluded, from either side of the membrane (Figure 11–5).
MBoC6 m11.05/11.05
When the transporter is saturated (that is, when all solute-binding sites are occupied),
the rate of transport is maximal. This rate, referred to as V max (V for velocity),
is characteristic of the specific carrier. V max measures the rate at which the
carrier can flip between its conformational states. In addition, each transporter
has a characteristic affinity for its solute, reflected in the K m of the reaction, which
is equal to the concentration of solute when the transport rate is half its maximum
value (Figure 11–6). As with enzymes, the binding of solute can be blocked by
either competitive inhibitors (which compete for the same binding site and may
or may not be transported) or noncompetitive inhibitors (which bind elsewhere
and alter the structure of the transporter).
As we discuss shortly, it requires only a relatively minor modification of the
model shown in Figure 11–5 to link a transporter to a source of energy in order
to pump a solute uphill against its electrochemical gradient. Cells carry out such
active transport in three main ways (Figure 11–7):
1. Coupled transporters harness the energy stored in concentration gradients
to couple the uphill transport of one solute across the membrane to the
downhill transport of another.
2. ATP-driven pumps couple uphill transport to the hydrolysis of ATP.
3. Light- or redox-driven pumps, which are known in bacteria, archaea, mitochondria,
and chloroplasts, couple uphill transport to an input of energy
from light, as with bacteriorhodopsin (discussed in Chapter 10), or from a
redox reaction, as with cytochrome c oxidase (discussed in Chapter 14).
Amino acid sequence and three-dimensional structure comparisons suggest
that, in many cases, there are strong similarities in structure between transporters
that mediate active transport and those that mediate passive transport. Some
bacterial transporters, for example, that use the energy stored in the H + gradient
across the plasma membrane to drive the active uptake of various sugars are
structurally similar to the transporters that mediate passive glucose transport
into most animal cells. This suggests an evolutionary relationship between various
transporters. Given the importance of small metabolites and sugars as energy
sources, it is not surprising that the superfamily of transporters is an ancient one.
We begin our discussion of active membrane transport by considering a class
of coupled transporters that are driven by ion concentration gradients. These proteins
have a crucial role in the transport of small metabolites across membranes
in all cells. We then discuss ATP-driven pumps, including the Na + -K + pump that is
found in the plasma membrane of most animal cells. Examples of the third class
of active transport—light- or redox-driven pumps—are discussed in Chapter 14.
Active Transport Can Be Driven by Ion-Concentration Gradients
Some transporters simply passively mediate the movement of a single solute from
one side of the membrane to the other at a rate determined by their V max and
rate of transport
Figure 11–5 A model of how a
conformational change in a transporter
mediates the passive movement of a
solute. The transporter is shown in three
conformational states: in the outwardopen
state, the binding sites for solute are
exposed on the outside; in the occluded
state, the same sites are not accessible
from either side; and in the inward-open
state, the sites are exposed on the inside.
The transitions between the states occur
randomly. They are completely reversible
and do not depend on whether the solutebinding
site is occupied. Therefore, if
the solute concentration is higher on the
outside of the bilayer, more solute binds
to the transporter in the outward-open
conformation than in the inward-open
conformation, and there is a net transport
of solute down its concentration gradient
(or, if the solute is an ion, down its
electrochemical gradient).
V max
transporter-mediated
diffusion
1/2V max
K m
simple diffusion
and channel-mediated
transport
concentration of
transported molecule
Figure 11–6 The kinetics of simple
diffusion compared with transportermediated
diffusion. Whereas the rate
of diffusion and channel-mediated
transport is directly proportional to the
solute concentration (within the physical
limits imposed by total surface area
or total channels available), the rate of
transporter-mediated MBoC6 m11.06/11.06
diffusion reaches a
maximum (V max ) when the transporter is
saturated. The solute concentration when
the transport rate is at half its maximal
value approximates the binding constant
(K m ) of the transporter for the solute and
is analogous to the K m of an enzyme
for its substrate. The graph applies to a
transporter moving a single solute; the
kinetics of coupled transport of two or
more solutes is more complex and exhibits
cooperative behavior.