DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

94
Passive transport (downhill transport)
Active transport (uphill transport)
High
Electrochemical potential
gradient of the substrate
Low
High
Electrochemical potential
gradient of the substrate
Low
SECTION I
GENERAL PRINCIPLES
Passive
diffusion
Facilitated
diffusion
ATP
Symport
Antiport
Primary active
transport
Secondary active
transport
Figure 5–4. Classification of membrane transport mechanisms. Red circles depict the substrate. Size of the circles is proportional to
the concentration of the substrate. Arrows show the direction of flux. Black squares represent the ion that supplies the driving force
for transport (size is proportional to the concentration of the ion). Blue ovals depict transport proteins.
ADP
the flux in passive diffusion; they are incorporated in the permeability
constant P. The permeability constant positively correlates with
the lipophilicity, determined by the partition between water and
organic solvents, such as octanol, and is also related to the inverse of
the square root of the molecular weight of the solute. At steady state,
the electrochemical potentials of all compounds become equal
across the plasma membrane. In the case of non-ionized compounds,
the steady-state concentrations are equal across the plasma membrane.
For ionized compounds, however, the steady-state concentration
ratio across the plasma membrane is affected by the membrane
voltage and given by the Nernst equation:
C
i
=
C
o
⎛ −zE F⎞
m
exp⎜
⎝ RT ⎟
⎠
(Equation 5–3)
The membrane voltage is maintained by the ion gradients
across the membrane.
Facilitated Diffusion. Diffusion of ions and organic
compounds across the plasma membrane may be facilitated
by a membrane transporter. Facilitated diffusion
is a form of transporter-mediated membrane transport
that does not require energy input. Just as in passive diffusion,
the transport of ionized and non-ionized compounds
across the plasma membrane occurs down their
electrochemical potential gradient. Therefore, steady
state will be achieved when the electrochemical potentials
of the compound on both sides of the membrane
become equal.
Active Transport. Active transport is the form of membrane
transport that requires the input of energy. It is the
transport of solutes against their electrochemical gradients,
leading to the concentration of solutes on one side
of the plasma membrane and the creation of potential
energy in the electrochemical gradient formed. Active
transport plays an important role in the uptake and efflux
of drugs and other solutes. Depending on the driving
force, active transport can be subdivided into primary
and secondary active transport (Figure 5–4).
Primary Active Transport. Membrane transport that
directly couples with ATP hydrolysis is called primary
active transport. ABC transporters are examples of
primary active transporters. They contain one or two
ATP-binding cassettes that are highly conserved
domains in the intracellular loop region and exhibit
ATPase activity. In mammalian cells, ABC transporters
mediate the unidirectional efflux of solutes across biological
membranes. The molecular mechanism by
which ATP hydrolysis is coupled to the active transport
of substrates by ABC transporters is a subject of current
investigation.
Secondary Active Transport. In secondary active transport,
the transport across a biological membrane of one
solute S 1
against its concentration gradient is energetically
driven by the transport of another solute S 2
in