Secondary Transporters Use One Concentration Gradient to Power the Formation of Another

Figure 13.8. ABC Transporters. The multidrug resistance protein (MDR) and the cystic fibrosis transmembrane
regulator (CFTR) are homologous proteins composed of two transmembrane domains and two ATP-binding domains,
called ATP-binding cassettes (ABCs).
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.3. Multidrug Resistance and Cystic Fibrosis Highlight a Family of Membrane Proteins with ATP-Binding Cassette Domains
Figure 13.9. Histidine Permease. In the histidine permease of S. typhimurium, the membrane-spanning regions (yellow
and orange) and ABC regions (blue) are on separate polypeptide chains (compare with Figure 13.8). ATP hydrolysis
drives the transport of histidine into the cell.
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.4. Secondary Transporters Use One Concentration Gradient to Power the
Formation of Another
Many active-transport processes are not directly driven by the hydrolysis of ATP. Instead, the thermodynamically uphill
flow of one species of ion or molecule is coupled to the downhill flow of a different species. Membrane proteins that
pump ions or molecules uphill by this means are termed secondary transporters or cotransporters. These proteins can be
classified as either antiporters or symporters. Antiporters couple the downhill flow of one species to the uphill flow of
another in the opposite direction across the membrane; symporters use the flow of one species to drive the flow of a
different species in the same direction across the membrane (Figure 13.10).
The sodium calcium exchanger in the plasma membrane of an animal cell is an antiporter that uses the electrochemical
gradient of Na+ to pump Ca2+ out of the cell. Three Na+ ions enter the cell for each Ca2+ ion that is extruded. The cost of
transport by this exchanger is paid by the Na+-K+- ATPase pump, which generates the requisite sodium gradient.
Because Ca2+ is a vital messenger inside the cell, its concentration must be tightly controlled. The exchanger has lower
2+
2+
2+
affinity for Ca
than does the Ca
ATPase (Section 13.2.1), but its capacity to extrude Ca
is greater. The
2+
2+
exchanger can lower the cytosolic Ca level to several micromolar; submicromolar Ca levels are attained by the
subsequent action of the Ca2+ ATPase. The exchanger can extrude about 2000 Ca2+ ions per second, compared with only
30 ions per second for the Ca2+-ATPase pump.
Glucose is pumped into some animal cells by a symporter powered by the simultaneous entry of Na+. The entry of Na+
provides a free-energy input of 2.2 kcal mol-1 (9.2 kJ mol-1) under typical cellular conditions (external [Na+] = 143 mM,
internal [Na+] = 14 mM, and membrane potential = -50 mV). This free-energy input is sufficient to generate a 66-fold
concentration gradient of an uncharged molecule such as glucose.
Secondary transporters are ancient molecular machines, common today in bacteria and archaea as well as in
eukaryotes. For example, approximately 160 (of approximately 4000) proteins encoded by the E. coli genome
appear to be secondary transporters. Sequence comparison and hydropathy analysis suggest that members of the largest
family have 12 transmembrane helices that appear to have arisen by duplication and fusion of a membrane protein with 6
transmembrane helices. Included in this family is the lactose permease of E. coli. This symporter uses the H+ gradient
across the E. coli membrane generated by the oxidation of fuel molecules to drive the uptake of lactose and other sugars
against a concentration gradient. The permease has a proton-binding site and a lactose-binding site (Figure 13.11). A
proton and a lactose molecule bind to sites facing the outside of the cell. The permease, with both binding sites full,
everts, releasing first the proton and then the lactose inside the bacterium. Another eversion places the empty sites on the
outside. Thus, the energetically uphill transfer of one lactose molecule is coupled to the downhill transport of one proton.
Further analysis of the three-dimensional structures is underway and should provide more information about their
mechanisms of action as well as the evolutionary relationships within this large group of ancient proteins.
These observations reveal how different energy currencies are interconverted. A single energy currency, ATP, is used by
P-type ATPases to generate gradients of a small number of types of ions, particularly Na+ and H+, across membranes.
These gradients then serve as an energy source for the large number of secondary transporters, which allow many
different molecules to be taken up or transported out of cells (Figure 13.12).
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.4. Secondary Transporters Use One Concentration Gradient to Power the Formation of Another
Figure 13.10. Secondary Transporters. These transporters employ the downhill flow of one gradient to power the
formation of another gradient. In antiporters, the chemical species move in opposite directions. In symporters, the two
species move in the same direction.
I. The Molecular Design of Life
13. Membrane Channels and Pumps
13.4. Secondary Transporters Use One Concentration Gradient to Power the Formation of Another