2018-2019 Sohag M1 B3 Physiology - Lecture 7,8,9 and 10 - Hassan Elalaf

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Transport Across the Cell Membrane

General information about this handout:

• This material is for Sohag Faculty of Medicine Students - 1st year

(M1) – Block3 (B3) – Physiology.
• Academic Year: 2018/2019
• Timing: During of 2nd and 3rd weeks of block 3.
• Required pre – lecture material (i.e. before you begin studying
transport across cell membrane you must briefly study these topics)
o Structure of cell membrane
o General Function of cell membrane
• Lecture number: 7, 8, 9 and 10 .
• Total lectures hours: 4 (Four) hours
• Total number of page: 19
• Original source: 2017 Comprehensive Textbook of Medical
Physiology - Pravati Pal
• Teaching staff: Dr. Hassna Mohamed Hassan Ali Elalaf

Handout Content
• Source material i.e. material which contain all information
to deliver Intended learning outcome (ILO) and written exams
will be based on these material.
• Figures
• Revision MCQs .
• Additional resource i.e. extra material to help student
gaining more understanding but WILL not be included in
exams.

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Transport across cell membrane

Materials (Fluid, electrolytes , nutrients or Gases etc) pass through the

cell membrane from inside of the cell to outside of the cell and vise verse
i.e. the opposite is also true.
The Transport process can be classified;
• According to method of transport (Fig.1);
o Passage through lipid bilayer of cell membrane.
o Passage through proteins of cell membrane.
o Vesicular transport (see later),
• According to ATP usage;
o Passive transport = No, ATP was used
o Active transport = ATP was used

Transport methods can be divided into :

• Passage through lipid bilayer (Leak).
o This method is suitable for;
ƒ lipid soluble substances, such as gases and fatty acids.
ƒ many small-uncharged molecules .

• Passage through (channels or carrier ) proteins.

o This method is suitable for;
ƒ water .
ƒ water soluble substances e.g. glucose and amino acids
ƒ Charged particles e.g. electrolytes Na, K etc.
ƒ Molecules with large molecular weight
This method is divided to ;
• A - Substance pass through protein channel which penetrate lipid
belayed from side to side.
• B - Substance combine with carrier protein located in the cell
membrane.

A - Protein channels
• They are tubular protein structures that connect the exterior with the
interior of cells .
• They are integral proteins
• The permeability of channels depends on molecular size, shape and
charge of the substance.
• There are two types,
o Water channels, They are designed for Water passage across
cell membrane. They are called aquaporins.
o Ion channels. They are designed for ion passage across cell
membrane

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Ion Channels
• Mechanism of action of ion channels, Along the length of the integral
protein, a pore ( opening ) and a lumen are present, through them the
Ions pass from one side of the membrane to the other. Thus, Ions cross
the membrane without entering the lipid bilayer of the membrane.
• Classification of Ion channels
o According to its selectivity;
ƒ Selective, allow passage of specific type of ions e.g.
Na only or K only.
ƒ Non selective, allow passage of multiple types of ions.
o According to its gating mechanism (Fig.2);
ƒ Non gated (leak channel), always
ƒ Gated channel (it is closed by a gate that open by
specific method).Mechanisms of gating are voltage-
gating, ligand-gating and mechanical-gating.

Voltage-gating (electrical gating)

Change in the membrane potential ( voltage difference across cell
membrane) beyond a certain value opens or closes the gate of the ion
channels e.g. ion channels in nerve , muscle and heart are mainly
voltage-gated channels like Na+ voltage gated channel and , K+ voltage
gated channel .

Ligand Gating (Chemical gating)

Binding of the channel with a ligand (Chemical substance)
causes opening or closure of the channel. Please, take care that the
chemical substance ( the key) is different from the passenger ( the ion)

B - Carrier protein
• They are protein structures inserted in the cell membrane , has no
lumen but can change their orientation so that they can move a
substance across cell membrane.
• They are integral proteins.
• There are three types; Uniport,symport and antiport (Fig.3)
o Uniport: A carrier protein that transports only one substance
o Symport (co-transport): A carrier protein that transport
two or more substances from one side of the membrane to
the other in the same direction.
o Antiport (counter-transport) : A carrier protein that
transport substances in opposite directions in which one
substance is transported to the inside of the cell and other
substance from inside the cell to the outside.

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Characteristics of Carrier-mediated Transport

• Competitive inhibition: Presence of different molecules (x and y)
with similar structure competes for the same carrier protein binding site
so one material (x) win the competition and get transported and other
material (y) failed to be transported (inhibited).
NB. In Co-transport (symport) and counter-transport( antiport) ,
competitive inhibition does not occur as substance x and y are dissimilar
but using the same carrier protein that has two different binding sites.
• Saturation (Fig.4) :The number of carrier proteins in a membrane is
limited. so once all carriers are occupied i.e. saturated by the material
(Z) , no, increase in transport can occur by simply increasing the
concentration of (Z).

Types of transport across the cell membrane (Fig.5).

A. Passive transports (Diffusion)
1. Simple diffusion 2. Facilitated diffusion
3. Osmosis (diffusion of water)

B. Active transports
1. Primary active transport 2. Secondary active transport

C. Vesicular transports
1. Exocytosis 2. Endocytosis

A. Passive transports (diffusion) (Fig.6)

Definition: Movement of substance according to its Electrochemical
gradients.

Characters of Passive transport;

1. Passive Transport is downhill; The movement of substance

according to Electrochemical gradient
o Chemical gradient
ƒ Substance move from high conc. to low conc.
ƒ It occur due to random movement of the substance
caused by their thermal energy. The motion varies
directly with temperature.
ƒ Chemical gradient occur for both charged and non
charged particles
o Electrical gradient

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ƒ A difference in charges between two adjacent areas

produces an electrical gradient that promotes
movement of ions toward the area of opposite charge.
• Positively charged ions (cations) tend to move
toward the more negatively charged area.
• Negatively charged ions (anions) tend to move
toward the more positively charged area
ƒ It occur due to the fact that Ions with like charges
(those with the same kind of charge) repel each other,
and ions with opposite charges attract each other.
ƒ Electrical gradient occur only for charged particles

2. Passive Transport does not utilize ATP .

Factors that Determine Rate of Diffusion;

I - Properties of the substance. II - properties of the membrane.

I - Properties of the Substance

A - Concentration and electrical gradients of the substance (see
before)
B - Permeability of the substance through the membrane.

B - Permeability of the Substance i.e. the ease at which substances pass

through the membrane.

The factors that determine the permeability are:

1. Lipid-solubility: As the membrane is a lipid bilayer, the
permeability of a substance is directly proportional to their lipid
solubility of the substance.
2. Molecular size: permeability is inversely proportional to the substance
molecular size.
3. Charge on the molecule: it will affect electrical gradient
4. Temperature: Rate of diffusion is high at higher body temperature as
temperature facilitates motion of molecules in the solution.
5.Number of channels and carriers in the membrane for a particular
substance : It directly proportional with permeability
6. Pressure gradient: Diffusion is more from high fluid pressure to low
pressure, as the pressure causes greater number of molecule to hit the
membrane.

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II - Properties of the membrane

A - Membrane cross-sectional area , Diffusion is directly proportional to
cross-sectional area
B - Membrane thickness of the membrane Diffusion is Inversely
proportional to thickness.

Types
• Simple = substance move through cell membrane without using
protein Carrier i.e. either through lipid layer or protein channels.
• Facilitated = substance movement through cell membrane is
facilitated by using a protein Carrier.
• Osmosis ( Diffusion of water), Discussed later

Facilitated diffusion differs from simple diffusion in that

1. Faster rate of transport.
2. Specificity, If the substance has its own specific carrier which has one
binding site that bind it and can not be used by dissimilar substance.
3. Competitive inhibition (discussed before)
4. Saturation (discussed before)

Osmosis ( Diffusion of water)SMOSIS

Background
• Any salutation (Fig.7) is composed of solutes dissolved in a solvent
i.e. Solution = Solutes + solvent
• Inside human body, the universal solvent is water .
• When you said that solution (x) is more concentrated than solution
(y), you point out two facts.
st
o 1 fact :Solution (x) has more solutes in comparison to
solution (y)
nd
o 2 fact : Solution (y) has more solvent (water) molecules in
comparison to solution (x) i.e. solution (y) has more water
concentration than solution(x).
• If you have Solution x ( more solute concentrated – less water
concentrated ) separated by a membrane from Solution y (less solute
concentrated – more water concentrated), the following can occur
(Fig.8);
o If membrane is permeable to solutes , solutes will diffuse
passively from high conc. of solutes to low conc., of solutes
according to conc. gradient of solutes
o If membrane is Non permeable to solutes but permeable
to water , solutes will not diffuse but water will move
passively i.e. diffuse (Osmosis) from (low conc. of solutes

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– high concentration of water) to (high conc., of solutes –

low concentration of water) according to conc. gradient of
water.

Definition1: Osmosis is the process of movement of solvent from the

solution with the lower concentration of solutes to the solution with
higher concentration of solute, when both the solutions are separated by a
membrane which allows the passage of solvent and not the solute
particles

Definition2: Osmosis is diffusion of water according to concentration

gradient of water

Factors affecting the ability of solute to cause osmosis;

• The solutes is not permeable i.e. . can not diffuse from side to side
• Concentration of that solutes in the solution
• Osmotic ability of solute is not related to the size, shape or charge
of solutes.

Osmotic Pressure (Fig.9)

Osmotic pressure is the pressure applied to the solution with higher solute
concentration to prevent osmotic flow of water to that solution.
Experimentally , osmotic pressure can be measured by measuring the
hydrostatic pressure applied to prevent water from entering the solution
with higher solute concentration.

How to quantify Osmolarity

• Osmole and Milliosmole
o The concentration of osmotically active particles is usually
expressed in osmoles (Osm). One osmole equals the gram
molecular weight (i.e. one mole) of the substance multiplied
by the number of freely moving particles each molecule
produce in solution. e.g.
ƒ One mole of glucose produce one osmole in solution
as glucose does not divide into smaller particle in
solution
ƒ One mole of NaCl, produce two osmole in a solution
as NaCl produce Na+ and Cl– in solution
ƒ One mole of CaCl2 produce 3 osmole in a solution as
CaCl2 produce Ca++, Cl– and Cl–.
o The milliosmole (mosm) is 1/1000 of 1 Osm i.e. 1000 mosm
= 1 Osm

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• Mole is the molecular weight (MW) of a substance in grams, i.e. the

gram molecular weight. For example, the MW of glucose is 180, so its
mole is 180 gm
Osmolarity and tonicity
• Osmolarity refers to total number of solutes in a solution
o Total number of solutes = solutes which can penetrate cell
membrane + solute which can not penetrate cell membrane.
ƒ Solutes which can penetrate cell membrane are
osmotically useless i.e. they can not cause osmosis
ƒ Solute which can not penetrate cell membrane are
osmotically useful i.e. can cause osmosis
• If you have multiple solution (A, B, C, and D ) and you compare their
similarity to each other , you can describe them as follow
o If solution A and B are equal in similarity then A is
isoosmotic to B
o If solution C is lower than B in osmolarity then is C is
hypoosmotic to B
o If solution D is higher than B in osmolarity then is D is
hyperosmotic to B.
• Tonicity refers to effect of solutes which can not penetrate cell
membrane i.e. osmoticlly active, on the cell volume
o Isotonic Solutions, which have tonicity same as intracellular
fluid, so these solution cause no water osmosis so cell
volume do not change
o Hypotonic ,Solutions with lower tonicity than intracellular
fluid, so these solution cause water osmosis into cell so cell
volume increase
o Hypertonic, Solutions with higher tonicity than intracellular
fluid, so these solution cause water osmosis out of the cell
so cell volume decreases.

B. Active transports

Definition: Movement of substance against to its Electrochemical

gradients and utilize ATP

Characters;
1. Uphill transport: Transport occurs against the electrochemical
gradient of the substance. so it need a source of energy
2. Utilize ATP. it is the source of energy so active transport are
susceptible to metabolic poisons which prevent ATP from being
produced or utilized

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Types;
1. Primary active transport. 2. Secondary active transport.

1- Primary Active Transport (Ion Pumps)

• Definition is the transport mechanism that directly utilizes

metabolic energy for the transport process. The ion pumps hydrolyze
ATP to ADP hence they are called ATPases and use energy in the
third phosphate bond for the transport process.
• The commonly occurring ATPase is Na+–K+ ATPase or Na+–K+
pump.

Na+/K+ ATPase (Fig.11)

• Na+-K+ ATPase is present in all eukaryotic cells.
• It is antiport that pumps K+ into the cell and Na+ out of the cell
against their concentration gradients. It is primarily responsible for
maintaining the high K+ and low Na+ concentration inside the cells.
• Structure and its Functional Aspects
• At the cytoplasmic side, the pump has ATPase activity and
binding sites for 3 Na+ and ATP and Phosphate binding site
• At the extracellular side the has binding sites for 2 K+ .
• Binding of three ions of Na+ and an ATP molecule with the
carrier on its cytoplasmic surface causes hydrolysis of ATP giving
rise to ADP and Pi.
• The phosphate group is bound to phosphate binding site.
• On activation, Na+-K+ ATPase pumps three Na+ ions out of
the cell and two K+ into the cell per each ATP Na+-K+ pump.
• Na+-K+ pump is an electrogenic pump as it forces net
positive charge to out of the cell,

2- Secondary Active Transport

Definition, Transfer one solute against its concentration gradient (from

low to high) by using the energy produced by gradient of another solute
(driver solute).

Background
Energy created by Na+ gradient - Na is the driver solute - is utilized for
transport of other solutes. The Na+ gradient is generated and maintained
by Na+-K+ pump (Active transport). Though the transport system of the
other solute by itself does not directly utilize energy, it depends on the
function of Na+-K+ pump.

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Steps; (Fig.12)
• The primary active transport of Na+ out of the cell by Na+-K+ pump
leads to decreased concentration of Na+ in the cytoplasm of the cells.
• This causes facilitated diffusion ( carrier mediated) of Na+ from the
out of the cell (high Na conc.) into the cells (Low Na. conc.).
• The carrier protein that transfers Na+ into the cell also transports
another substance or ion against their conc. gradient .
• The carrier protein transports the other substance simultaneously
with sodium making usage of Na conc. gradient created by the Na- K
pump so it is secondary active transport.
• The carrier protein may be
o Symport i.e. carry Na and other substance in the same
direction.
o Antiport i.e. carry Na and other substance in opposite
directions.

C. Vesicular transports

Definition, The transport process that occurs by either fusion of vesicle

or formation of vesicle is called as vesicular transport.

Types (Fig. 13):

• Exocytosis = Fusion of vesicle with the cell membrane and release of
the cell vesicle content – particles /substances- to exterior .
• Endocytosis = Formation of vesicle from the cell membrane and
uptake of an outside of the cell particle/substance into the cell interior.

NB. Cell use vesicular transport method when the particle/substance can
not be transported by diffusion or active transport process.

Characters;
1. It has No, relation to conc. gradient i.e. it may go with or against conc.
gradient.
2. It may Utilize ATP.
3. It affects cell membrane surface area.
• Removing areas of cell membrane in process of vesicle
formation in endocytosis.
• Adding areas to cell membrane in process of exocytosis

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Mechanism of Vesicular transport

I - Endocytosis mechanism (Fig.14):

• Vesicle formation, The substance makes contact with the cell
membrane that invaginates to form an endocytic vesicle.
• Vesicle detachment, The non-cytoplasmic side of the
membrane then fuses and the vesicle is pinched-off into the
cytosol.
II - Exocytosis mechanism :
• Vesicle formation, The substance are packed within the vesicle
inside the cell.
• The vesicle move toward cell membrane and contact it.
• The vesicle fuse with the cell membrane.
• The vesicle release its content to cell exterior.

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Figures

Fig.1

Fig.2

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Fig.3

Fig.4

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Fig.5

Fig.6

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Fig.7

Fig.8

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Fig.9

Fig.10

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Fig.11

Fig.12

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Fig.13

Fig.14

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Revision MCQs
1. If substance X is uncharged and more concentrated in side A
in comparison to side B, the movement of X from side A to side
B is
A - Passive process. B - Require use of ATP
C - Occur according to Electrical gradient
D - Against conc. gradient.

2. All of the following are characters of facilitated diffusion

except,
A - It occur according to conc. gradient
B - It does not use ATP
C - It use a protein carrier
D - It utilize a protein channel

3. In order that a substance can leak through lipids of cell

membrane, it is preferable to be,
A - Very large molecule B - An ion
C - Water soluble substance D - Uncharged particle

2nd active transport is so named as

A - It is less important than 1ry active
B - It consume less energy
C - It depend on 1ry active
D - It occur less frequently

Additional resource
Title: Human Physiology: From Cells to Systems, Ninth Edition
Author: Lauralee Sherwood

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