Under normal cellular conditions, it takes very little transfer of protons
across the membrane before the electric potential ΔVthat is generated is
equal to the chemical potential due to the difference in the proton con-
centrations. Thus, the transfer of protons does not impact on the proton
concentrations on either side. For example, if you have a 10-fold excess of
protons on one side of the membrane and add a protonophore, a molecule
that allows the transfer of protons, but nothing else, across the membrane,
such as nigericin, you would assume that the protons transfer until the
chemical and electric potentials balance without changing the proton
concentrations.
In a mitochondrial membrane, the ratio of proton concentration is
about 10:1, corresponding to a chemical potential of 60 meV. The elec-
tric potential is about 180 meV so the total free energy to drive protons
across the membrane is 240 mV. The oxidation of NADH requires about
2.3 eV, so roughly 10 protons are pumped across the membrane per NADH
oxidized. Remember that volt (V) is a unit of electrical potential whereas
an electron volt (eV) is a unit of energy. One eV is the amount of free
energy required to transfer 1 mol of a singly charged positive ion across
a membrane with an opposing electric potential of 1 V. For example, the
free-energy transfer of 1 mol of protons across a membrane with a 200 mV
potential is 200 meV.
Transporters
Transport proteins selectively mediate the passage of molecules across
the membrane, which is otherwise impermeable. More than 360 trans-
porter families have been identified, highlighting the critical role of
transport processes in cells. For example, the major facilitator super-
family transfers its substrates against concentration gradients by coupling
the transfer to a second, energetically favorable movement. These trans-
porters have 12 transmembrane helices, which are seen to be organized
into two domains in the structures of LacY, which mediates the coupled
transport of lactose with protons, and GlpT, which transports glycerol
3-phosphate and phosphate (Figure 18.2). The two domains are related
to each other by an approximate 2-fold symmetry axis. These structures
support the idea that transport occurs through a process of alternating
access, in which the protein undergoes domain changes that alternately
provide substrate access to one side of the membrane or the other, but
never to both simultaneously.
Glutamate transporters play a critical role in the control of neurotrans-
mitters, small diffusible molecules that transmit nerve impulses across
synapses. Neurotransmitters are used for communication between neurons,
and many drugs, such as cocaine or Prozac, target proteins that inhibit
neurotransmitter transporters. The predominant excitatory neurotransmitter
394 PART 3 UNDERSTANDING BIOLOGICAL SYSTEMS USING PHYSICAL CHEMISTRY
