Transmembrane Transport of

Ions & Small Molecules

 Biomembranes are Selectively Permeable

• Lipid bilayer structure

results in selective
permeability:
– Meaning only
certain types of
substances can
move through

Figure 11-1
 Mechanisms of Transmembrane
Transport

• Simple (Passive) Diffusion

• Facilitated Diffusion
• Primary Active Transport
• Secondary Active Transport (Cotransport)
 Simple Diffusion

• Diffusion refers to the movement of permeable substances

across a membrane, from a region of higher concentration to
one of lesser concentration. There is no expenditure of
energy.
• Diffusion occurs spontaneously because entropy increases as
a substance moves from high conc. to low conc.
– ΔG assumes a negative value since the products have
more entropy and less free energy
ΔG = Gproducts - Greactants
ΔG = ΔH – TΔS

H-enthalpy
S-entropy
What Determines Diffusion Rate Across a
Membrane?

• Concentration gradient across membrane

• Size of the diffusing particles
• Electric potential across membrane (for charged
particles)
• Hydrophobicity
 Hydrophobicity
• Hydrophobicity measures the degree to which a substance is
hydrophobic.
– measured by the substance’s partition coefficient (K)
– K is the equilibrium constant for it’s partition between oil &
water
= [in oil] / [in H2O]
– the higher the K for a substance, the more lipid-soluble it is
and the faster it’s rate of movement across a bilayer.

• What influences a substance’s hydrophobicity?

– proportion of uncharged regions in a substance
Example: a long chain fatty acid is more hydrophobic than a
shorter chained one
Which are More Hydrophobic?

OR

OR
 How do Impermeable Substances Move
Through Membranes?
• Require transport proteins: pumps, channels and transporters
• These protein-mediated processes may or may not need
energy
• Multiple transport proteins may function together (fig 11-3)
 Transport Protein Mediated Processes
• Facilitated Diffusion
– substance moves from region of higher conc to lower conc with no
expenditure of energy
– typically involves use of channel proteins or uniport transporters
– E.g., glucose can enter cells via facilitated diffusion

• Primary Active Transport

– substance moves from a region of lower to one of higher
concentration with an expenditure of energy
– requires use of proteins called pumps, which are ATPases

• Secondary Active Transport (Cotransport)

– energetically unfavorable transport of a target substance against its
conc gradient is coupled to the energetically favorable movement of
an ion down its electrochemical gradient
– can be symport or antiport cotransport
 Membrane Transport Proteins
#1: ATP powered pumps

• primary active transport

• substance moves from a
region of lower to one of higher
concentration
• expenditure of energy
• requires use of proteins called
pumps, which are ATPases

Figure 11-3a
 Membrane Transport Proteins
#2: Ion channels
• these proteins transport ions,
water and small hydrophilic
molecules

Channels may be gated or non-

gated (ungated):
• Non-gated channels are
always open, as such they are
often called “leaky” channels.

• Gated channels are closed

until opened by a stimulus

Figure 11-3b
Membrane Transport Proteins
#3: Transporters

Figure 11-3c
 Comparing Simple Diffusion & Uniport
Transport
• Uniport transport, a form of facilitated diffusion, involves
the transport of small hydrophilic molecules through a
membrane.

• Uniport transport differs from simple diffusion:

– Rate of uniport transport is higher
– K is irrelevant (molecule never enters the hydrophobic core of the
phospholipid bilayer)
– There is a maximal Vmax
– Transport is reversible (direction changes depends on the
concentration gradient
– Transport is specific
 Glucose Uniport Transporters (GLUT)

• Humans encode 12 glucose

uniporters (GLUT 1-12)
• they are isoforms and are
tissue-specific
– Eg) GLUT 1 is expressed
in erythrocytes and
GLUT2 in liver cells
Osmotic pressure causes H2O to move
across membranes
Figure 11-7: Aquaporin expressing frog
oocytes burst in hypotonic solution

Oocytes at the top microinjected with mRNA encoding aquaporin

Figure 11-8: Structure of Aquaporin
4 Classes of ATP Powered Pumps
Figure 11-10: Model of Ca2+ ATPase
Structure of Catalytic a-subunit of
Muscle ATPase
Figure 11-12: Na+/K+ ATPase in PM
Effects of V-class H+ pumps on H+ conc.
& electric potential gradients

V-class pump only

V-class pump w/
Cl- channel
 ATP-powered ion pumps generate &
maintain ion gradients across membranes
 ABC Superfamily
• About 50 ABC superfamily pumps are known in mammals
• They transport lipids, sugars, and other molecules.
• E.g, MDR1 and CFTR
– MDR1 transports lipid-soluble substances out of cells
– CFTR transport Cl-

• Also found in bacteria

– import nutrients from environment
 Flippase Mechanism

• Used by ABC
superfamily pumps
that transport lipid
soluble substances
 Gated & Ungated Channels
• Gated channels are closed until opened by a stimulus:
– Chemical (ligand) gated
– Voltage gated

• Non-gated (ungated) channels are always open, as such they

are often called “leaky” channels.
– help to maintain a membrane resting potential
– Major nongated channels are:
• Na+
• K+
• Cl-
• Ca2+
– K+ is the most important ion in maintaining the value of the
membrane potential.
 Figure 11-18: Generation of a
transmembrane electric potential (voltage)
depends on selective movement of ions
across semi-permeable membrane
Structure of Resting Bacterial K+ Channel
Figure 11-25
 Cotransport
• Examples include:
– Na+/H+ antiporter
– Cl-/HCO3- antiporter
– 2Na+/glucose symporter
– 3Na+/Ca+2 antiporter

Figure 11-26, 8th edition

Figure 11-26: 2 Na+/1 Leucine Symporter
 Co-transporters and pH

• The activity of membrane transport proteins that regulate the

cytosolic pH of mammalian cells changes with pH.

• For example, the Na+/H+

and Na+HCO3-/Cl-
antiporters that act to
increase cytosolic pH, are
activated when cytosolic
pH decreases.

• In contrast, the Cl-/HCO3-

antiporter is activated at
high pH, and it leads to a
reduction of cytosolic pH.
 Transport Across Epithelial Membranes:
Transcellular Glucose Transport from Small Intestine
Lumen
The Na+/K+ ATPase
inside the basolateral
surface membrane
generates Na+ and K+
conc gradients. The
outward movement of
K+ ions through
nongated K+ channels
generates an inside-
negative membrane
potential across the
plasma membrane.
The Na+ conc gradient
and the membrane
potential are used to
drive the uptake of
glucose from the
intestinal lumen by the
2 Na+/1 glucose
symporter located on
the apical surface
membrane
 Rehydration Therapy

• States of intense dehydration caused by disease,

chemotherapy, or physical stress can be treated by the
ingestion of water, sugar and salt to stimulate the Na+/glucose
symporter. Why?
• This principle is the basis for the ingredients of Gatorade and
similar drinks.
Transport Across Epithelial Membranes:
Acidification of Stomach Lumen by Parietal Cells
 Proton Pump Inhibitors

• Your stomach produces acid to help break down food so it is easier

to digest.
– In certain circumstances, this acid can irritate the lining of your stomach
and duodenum causing indigestion and even ulceration and bleeding.
• The proton pump inhibitors work by completely blocking the
production of stomach acid.
• They do this by inhibiting (shutting down) a system in the stomach
known as the proton pump.
• full name for this system is 'hydrogen-potassium adenosine
triphosphate enzyme system'.
 Ouabain, A Cardiac Glycoside

• Endogenous ouabain is found in mammals

– acts as a steroid hormone
– may be implicated in hypertension
• medicinal value is as a heart stimulant.

• Mechanism: Ouabain blocks the Na+/K+ pump of muscle.

– Consequently: Na+ gradient is destroyed, cytosolic Ca2+ levels
remain high, muscle contracts more strongly
– Ouabain directly causes cytosolic Na+ levels to increase,
Na+/Ca2+ antiporter does not function as efficiently, cytosolic
Ca2+ levels increase