Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University
Chapter
3

Content
s
3.3.1 General
Introduction
3.3.2 Passive Transport
3.3.3 Facilitated Diffusion
3.3.4 Active
Transport
3.3.5 Several topic for ion
pumps
3.3.1 General
Introduction
• Transport of nutrients, ions, and excretory
substances from one side to the other is a major
function of the cell membrane. A number of
different means have been developed to fulfill this
function.
• The interior of the lipid bilayer is hydrophobic and
blocks the passage of almost all water-soluble
molecules. But cell live and grow by exchanging
molecules with their environment, so that various
water-soluble molecules must be able to cross the
plasma membrane. A few of these solutes can
simply diffuse across the lipid bilayer, but the vast
3.3.1 General
Introduction
majority can not. Instead, their transfer depends
on membrane transport proteins that span the
membrane and provide private passages across
it for specific substances.
• Movements of molecules “downhill” from a
region of high concentration to a region of low
concentration occur spontaneously, provided a
pathway exits. Such movements are called
passive, because they need no other driving force.
3.3.1 General
Introduction
• To move a solute against its concentration
gradient, however, a transport protein has to do
work: it has to drive the “uphill” flow by coupling
it to some other process that provides energy.
Transmembrane solute movement driven in this
way is termed active transport.
• Why transport ?
• Ensure the essential molecular enter the cell
• Remove waste
• maintain a constant internal environment
3.3.1 General
Introduction
The meaning of selective permeability
• Plasma membrane is a selective permeable
barrier between the cell and the extracellular
environment.
• its selective permeability ensures that
essential molecules such as ions, glucose, amino
acids, and lipids readily enter the cell, metabolic
intermediates remain in the cell, and waste
compounds leave the cell.
• The selective permeability of plasma membrane
allows the cell to maintain a constant internal
environment.
3.3.2. Passive Transport
• Simple diffusion.
• The simplest form of transport is passive
diffusion. It is a real freebie; it does not even
need helpers.
• Fat-soluble molecules and small uncharged
molecules can pass directly through the lipid
bilayer by simple diffusion.
high concentration
Concentration gradient
low concentration
• Simple diffusion
Few molecules, such as Oxygen, carbon dioxide,
nitrogen (O 2, CO 2, N 2 ), diffuse easily through
membrane because they have no charge (partial
or complete) to interact with water.
such urea and ethanol, can diffuse across an
artificial membranes composed of pure
phospholipid or of phospholipid and
cholesterol. hydrophilic hydrophobic
• Hydrophobic molecule molecule
molecules (oils) have

also no trouble
permeating
In the process, no metabolic energy is expended,
no specific transport proteins need, movement
down its chemical concentration gradient, called
passive diffusion, or simple diffusion.
High Low
Concentration Concentration
Small gaseous O2 permeable
molecules CO2
N2
Small glycerolpermeable
uncharged polar
molecules ethanol
relative permeability of a pure phospholipid bilayer
• Passive diffusion is driven by the thermodynamic

action. The diffusion rate of any substance is de-
termined by its concentration gradient across the
layer, its hydrophobicity, its size and any electric
potential across the membrane affected charged
molecules.
The greater concentration gradient of the
substance across the layer, or the higher its
hydrophobicity, or the smaller molecule, the higher
its diffusion rate is.
Small Urea,
Water
uncharged Slightly
polar permeable
molecules
Charged Amino acids
ATP
polar
molecules Nucleic acids
protein
Impermeable
Ions H+ Na+ Cl-

HCO3- Ca2+
Mg2+ K+
Impermeable
relative permeability of a pure phospholipid bilayer

3.3.3. Facilitated
Transport
• In most human cells
there is an unequal Na
150 mM Cl
distribution of ions: Na
10 mM
Na + 10 mM inside; organic anions
150 mM outside.
- 70 mV
K
5 mM K
K + 150 mM
150 mM
inside;
5 mM
•outside.
anions: proteins inside; Cl -
outside
3.3.3. Facilitated
Transport
Distribution of ions across the cell membrane
Component outside (mM) inside (mM)
K+ (potassium ion) 5 150
Na+ (Sodium ion) 150 10
Ca+2 (calcium ion) 1.8 ＜ 0.0005
Cl- (chlorine ion) 110 3
Mg+2 (magnesium ion) 1.5 0.8
Amino acids, proteins 9 138
• So the cell membrane is called selective

permeability barrier that maintains distinct
internal and external cellular environments.
• It must get supports otherwise those large
molecules and ions do not penetrate bilayer.
3.3.3. Facilitated
Transport
Overview
• The kinetics of facilitated (with a helper) trans-
port is different from those of simple diffusion. In
the latter, the rate of diffusion is proportional to
the concentration of the diffusing molecules; the
more of them, the more of them
will diffuse across the
rate o f tran sp o rt
membrane per unit time.

fa cilitated diffu s io n
• The rate of facilitated

diffusion is far higher than s im p le d iffus io n
passive diffusion.
Cheng Xiaoli
[c on c. tranZhengzhou
sp orted mUniversity
olecule]
3.3.3. Facilitated
Transport
Overview
• The rate of facilitated diffusion is limited by the
availability of the uniporter molecules rather than
throughout the phospholipid bilayer. Once all the
helpers are saturated, the increasing concentra-
tion of diffusing molecules will only increase a
waiting line for the helper and will not increase
rate of transport.
• Consequently, there is a maximum transport rate
Vmax that is achieved when the concentration
gradient across the membrane is very large and
each uniporter is working at its maximal rate.
3.3.3. Facilitated
Transport
Overview
• Facilitated transport is specific. Each

uniporter transports only a single
species of molecule or a single group of
closely related molecules.

3.3.3. Facilitated
Transport
• Ion channels
The simplest form of a helper-facilitator is
an ion channel.
• Ion channels are usually small proteins
that span the membrane and have central
water-filled pores and its outside surface
is hydrophobic and the inside hydrophilic.
hydrophobic hydrophilic

3.3.3. Facilitated
Transport
• Ion channels
•Most ion channels are gated and open transiently
in response to a specific stimulus, such as a change
in membrane potential or the binding of a ligand or
a chemical (phosphorylation) or electrical
stimulus .
Ligand-Gated
channels

3.3.3. Facilitated
Transport
• Ion channels
• Voltage-gated channels-– respond to
voltage changes in membrane potential.
＋＋＋＋＋
＋
＋＋＋＋
＋＋
－
＋－
－－－－－－－－－
－－－
－
Electrochemical gradient
3.3.3. Facilitated
Transport
• Ion channels
• Ion channels have two distinct characters:
high transport speed (high to 106 inos/s) and
specific selectivity. The speed is above 1000
times higher than any carrier protein.
• The forces driving the transport are due to
concentration gradients and electric potential
gradients.
• Above 100 kinds of ion channels had be
discovered on various cell’s plasma membrane.
3.3.3. Facilitated
Transport
• Transporters
(Carriers)
• Transporters consist in almost all biomembrane
and move a wide variety of ions and molecules
across the membranes.
• Don’t like channel protein, it is
necessary that molecule or ion
transported link to the
transporter. Each kind of trans-
porter links to special solution
molecule, and introduces them
from the side to another side of
the membrane by the changing
the conformation of itself. Cheng Xiaoli Zhengzhou University
3.3.3. Facilitated
Transport
• Transporters
(Carriers)
• Three types transporters have been
identified
Uniporters Transported molecule
transport a
single type of
molecule down
its concentration
gradient via
• facilitated
Facilitated diffusion requires no external
diffusion.
source of energy.
3.3.3. Facilitated
Transport
• Transporters
(Carriers)
Antiporters and symporters couple the
movement of one type of ion or molecule
against its concen-tration gradient with
the movement of one or more different
ions down its concentration gradient.
transported molecule
Symport
3.3.3. Facilitated
Transport
• Transporters
(Carriers)
For example , glucose, which is needed in
large amounts by cells for energy, is one
substance commonly cross the plasma
membrane into cells with the aid of
uniporters.

3.3.3. Facilitated
Transport
• Transporters
(Carriers)
Glucose transport also can catalyze the
net export of glucose from the cytosol to
the extracellular medium exterior when
the glucose concentration is higher inside
the cell than outside.

3.3.3. Facilitated
Transport
• Both carriers and channels are multi-
pass tran-smembrane proteins.
• A channel protein discriminates mainly
on the basis of size and electric charge: if
the channel is open, molecules small
enough and carrying the appropriate
charge can slip through, as though an
open, but narrow,
• A carrier proteintrapdoor.
acts more like a
turnstile: it allows passage only to solute
molecules that fit into a binding site on
the protein, and it transfers these
molecules across the membrane one at a
3.3.4. Active
Transport
Often the transport has to happen in
the direction opposite to the
electrochemical or concentration
gradient. In order to accom-plish this,
membranes have evolved elaborate
schemes to pump the substance ( ions
tration to a compartment
or moleciles) with
from the area of higher
smaller
concen-tration.
concen- All these schemes
cost the cell energy (hydrolysis of ATP
or light energy) and thus are called
active transport. It is sensitive to
inhibi-tors that stop ATP synthesis.
3.3.4. Active
Transport
ATP-powered pumps
• ATP-powered pump is an ATPase that use
the energy of ATP hydrolysis to move ions
or small molecules across a membrane
against a chemical concentration or
electric potential gradient or both.

3.3.4. Active
Transport
ATP-powered pumps
• All ATP-powered pumps are

transmembrane proteins with one or
more binding sites for ATP located on
the cytosolic face of the membrane.
• Although these proteins commonly are
called ATPase , they normally do not
hydrolyze ATP into ADP and Pi unless
ions or other molecules are
simultaneously transported.
3.3.4. Active
Transport
• There are four classes ATP-powered
pumps:
-- P- class ion pumps
-- F-/ V- class ion pumps
-- ABC (ATP-binding cassettes)
superfamily

3.3.4. Active
Transport
• The generally characteristics of ATP-
powered pumps:
-- are transmembrane
proteins
-- have one or more ATP binding site
(all in cytosolic side)
-- coupling ATP hydrolysis/synthesis
and ion transport

3.3.4. Active
Transport
Four subunits of P-class pumps
• H+ pump: plants, fungi, bacteria cell memb.

• Na+ / K+ pump: animal cells membrane
• H+ / K+ pump: mammalian stomach cells
• Ca2+ pump: sarcoplasmic reticulum membrane in
muscle cells
• during the transport process, at least one of the
αsubunits is phosphorylated (hence the name P-
class pumps) and the transported ions are
thought to move through the phosphorylated
subunit. Cheng Xiaoli Zhengzhou University
3.3.4. Active
Transport
P-class pumps functions
• Maintains the low Na+ and high K+concentrations of

animal cell Na
150 mM Cl
• Pump Ca2+ into ER in muscle Na

10 mM
organic anions
• Pump Ca out of the cytosol into

- 70 mV
2+
K
K
the external medium

5 mM
150 mM

3.3.4. Active
Transport
F- / V- class proton pumps
• F- and V- class pumps are similar to one
another but unrelated to and more complicated than P-
class pumps. All known F- and V- class pumps transport
only protons, in a process that does not involve a
phosphoprotein intermediate. K+
Na -K
+
- +
ATPase
• V- class pumps generally function ATP
ADP+Pi
ATP H+ ADP+Pi
to maintain the low pH of lysosomal Na+
and other acidic vesicles in animal H +
cells by pumping protons from the lysosome

H+
+ +
H + H+
+
cytosolic to the exoplasm against a H+

proton electrochemical gradient. ATPase
ATP H+ ADP+Pi
ATP
3.3.4. Active
Transport
F-class proton pumps
• On Inner mitochondria membranes
• On Bacterial plasma membrane
• In contrast to V pumps, F pumps generally function to
power the synthesis of ATP from ADP and Pi by movement
of protons from the exoplasmic to the cytosolic face of
the membrane down the proton electrochemical
gradient.

3.3.4. Active
Transport
ABC superfamily
– Two transmembrane (T) domains: passage
– Two cytosolic (A) domains: ATP-binding
ABC superfamily functions

• Transport amino acid, sugar, peptide
transporters (Bacterial )
• Transport phospholipids, cholesterol, lipophilic
drugs, other small molecules
3.3.4. Active
Transport
• Cotransporters
• Cotransporters mediate coupled reactions in
which an energetically unfavorable reaction
(uphill movement of molecules) is coupled to an
energetically favorable reaction (symporter and
antiporter).
• Here, ATP pump use energy from hydrolysis of
ATP, whereas cotransporters use the energy
stored in an electrochemical gradient. This latter
process sometimes is referred to as secondary
active transport.
Na+-driven
glucose
symport
Passive
transport
Transport of glucose into and out of intestinal epithelial

Cheng Xiaoli cells.
Zhengzhou University
3.3.5. Several topic for ion
pumps
The specific ionic composition of the cytosol
usually differs greatly from that of the surrounding
extracellular fluid.
Invertebrate(Squid axon) vertebrate (mammalian)
ion Cell(mmol/L) Blood (mmol/L) ion Cell(mmol/L) Blood (mmol/L)
K+ 400 20 K+ 139 4
Na+ 50 440 Na+ 12 145
Cl- 40-150 560 Cl- 4 116
Ca2+ 0.0003 10 Ca2+ 0.0002 1.8
Mg2+ Mg2+ 0.8 1.5
X- - 300-400 5-10 X- 138 9

X : represents proteins, which have a net negative charge at theCheng
neutral pH Zhengzhou
Xiaoli of blood and cells.
University
pumps
The ion pumps are largely responsible for
establishing and maintaining the usual ionic
gradients across the plasma and intracellular
membranes. Cells expend considerable energy to
carry out this task.
For example, to transport ions,
up to 25% of the ATP produced by
nerve and kidney cells is
consumed, and up to 50% of that
in human erythrocytes; in both
cases, most of this ATP is used to
power the Na+-K+ pump.
pumps
Studies on the effects of poisons
Na
Na
150 mM
75 mM Cl
150 mM Cl
Na
Na
In cells treated 75 mM
10 mM
10 mM
organic anions
- 70 mV
organic anions
with poisons - 70 mV
K
K K
5 mM K 75
5mmM
M
150 mM
mM
150 mM 75
75 mM
Eventually
treated cells Die
Cells die: partly because protein synthesis requires a
high concentration of K+ ions and partly because in the
absence of a Na+ gradient across the cell membrane, a
cell cannot import certain nutrients such as amino
pumps
• Na / K - ATPase
Na/K ATPase is an important P-class ion pump to maintain
the intracellular Na+ and K+ concentrations in animal cells.
• The Na/K-ATPase uses the energy of ATP hydrolysis to pump three

Na+ ions out of the cell and two K+ ions into the cytosol against their
electrochemical gradient. This enzyme is an important example of
primary active transport. Cheng Xiaoli Zhengzhou University
pumps
• Na/K-ATPase
Here the energy of a phosphate (shown

in red) is used to exchange sodium
atoms for potassium atoms.
pumps High-
affinity
binding
sites
The mechanism of action of Na/K- low-
ATPase Sodium
affinit
y
bindin
g
sites
low-
affinit
High- y
affinity bindin
binding g
sites sites
Potassium Cheng Xiaoli Zhengzhou University

pumps
• Ca ATPase
2+
Ca2+ Ca2+
Ca2+
•ATP- dependent Ca 2+ -pump

Ca2+
•P-class ion pump Ca2+ Ca2+Ca2+
• transport Ca2+ out of the cell or

into intracellular Ca 2+ storage ag
ainst its Ca2+ concentration gradi Ca 2+
ent by using the chemical energy
derived from ATP hydrolysis
• help maintain the concentration ADP+Pi ATP

Ca2+
of free Ca2+ in the cytosol at a low l
evel Cheng Xiaoli Zhengzhou University
pumps
• Ca ATPase
2+
Ca2+ Ca2+ Ca2+
• The catalytic cycle of ATPase

can be reversed after a Ca2+ gr
adient is formed across the ves
Ca2+
Ca2+
Ca2+
icular membrane
• During the reversal, Ca2+ Ca2+
leaves the vesicle through the
ATPase and ATP is synthesized f
rom ADP and Pi using the energ
y derived from the Ca2+ concent ATP ADP+Pi Ca2+
ration gradient Cheng Xiaoli Zhengzhou University

pumps
• Ca ATPase
2+
•Ca 2+ high concentration
in the lumen of the ER
serves as the major
internal reservoir form
which Ca 2+ is released
to the cytosol.
Skeletal and
cardiac muscle
contraction is
activated when
Ca 2+ is released
from the SR lumen
to the cytosol via
theCheng
CaXiaoli
release
2+ Zhengzhou University
Key
Points
• Please explain the following terms:
simple diffusion, facilitated diffusion, ion
channels, Na/K-ATPase, symport, uniport,
antiport and Cotransporter
• Please compare the features distinguish
uniport transport from passive difusion

Cheng Xiaoli Zhengzhou University

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