3. • barrier to water and water-soluble substances
ions glucose
urea
Lipid Bilayer:
CO2
O2
N2
halothane
H2O
4. Ion Concentrations
The maintenance of solutes on both sides of the
membrane is critical to the cell and homeostasis
Helps to keep the cell from rupturing
Concentration of ions on either side varies widely
Na+
and Cl-
are higher outside the cell
K+
is higher inside the cell
Must balance the number of positive and
negative charges, both inside and outside cell
5.
6.
7. Composition of ECF is maintained by different
systems like nervous , endocrine, CVS, GIT, renal ,
respiratory in a coordinated fashion
Composition of ICF is maintained by cell
membrane which mediates the transport of
materials b/w ICF and ECF through different
transport mechanisms.
8.
9. Membrane Transport Proteins
Many molecules must move back and forth from inside
and outside of the cell
Most cannot pass through without the assistance of
proteins in the membrane bilayer
Private passageways for select substances
Each cell has specific set of proteins
11. Permeability of a membrane
Anything that passes between a cell and the
surrounding ECF must be able to pass through the
plasma membrane.
If a substance can pass thru the membrane, the
membrane is said to be permeable to that substance;
if a substance cannot pass, the membrane is
impermeable to it.
The plasma membrane is selectively permeable in
that it permits some substances to pass through while
excluding others.
12. Impermeable Membranes
Ions and hydrophilic
molecules cannot easily
pass thru the
hydrophobic membrane.
Small and hydrophobic
molecules can
13. 2 Major Classes of proteins
Carrier proteins – move the solute across the membrane
by binding it on one side and transporting it to the other
side
Requires a conformation change
Channel proteins – small hydrophilic pores that allow for
solutes to pass through (watery spaces)
Use diffusion to move across
Also called ion channels when only ions moving
Called aquaporins if water is moving thru them
15. Carrier vs Channel
Channels, if open, will let solutes pass if they have the
right size and charge
Trapdoor-like
Carriers require that the solute fit in the binding site
carriers are specific like an enzyme and its substrate
16. Both the channel proteins and
carrier proteins are usually highly
selective in the types of molecules
or ions that are allowed to cross the
membrane.
These proteins are also present in
membranes of cell organelles
18. Membrane Ion Channels
Passive, or leak, channels – always open
Gated which open and close
Chemically (or ligand)-gated channels – open
with binding of a specific neurotransmitter (the
ligand)
Voltage-gated channels – open and close in
response to changes in the membrane potential
Mechanically-gated channels – open and close in
response to physical deformation of receptors
Types of plasma membrane ion channels
22. KEY WORDS
Solvent: (relatively large amount of a substance which is
the dissolving medium; in the body is water).
Solute: (relatively small amount of a substance which is
the dissolved substance and it dissolves in the solvent).
Solution: is a homogenous mixture of a solute in a
solvent.
Concentration: of a solvent is the amount of solute
dissolved in a specific amount of solution.
Concentration gradient: difference in the concentration
of a solute on two sides of a permeable membrane.
Equilibrium: exact balance between 2 opposing forces.
Dynamic: continuous motion or movement.
23. Types of Cellular Transport
1 Passive Transport
cell doesn’t use energy
1. Diffusion (simple & facilitated)
2. Osmosis
2 Active Transport
cell does use energy
1. Primary active transport
2. Secondary active transport
high
low
This is
gonna
be hard
work!!
high
low
Weeee!!!
•Animations of Active
Transport & Passive
Transport
26. Two major modes of membrane transport
I. Simple (Passive)DiffusionI. Simple (Passive)Diffusion
no carriers is involvedno carriers is involved
There are two major modes of mediated diffusion:
passive transport (or facilitated diffusion) and active
transport
II. Mediated DiffusionII. Mediated Diffusion
is carried out by proteins,is carried out by proteins,
peptides, and small molecularpeptides, and small molecular
weight carriersweight carriers
((ions, uncharged organic compounds,
peptides, and even proteins can be
transported)
•Molecules that are transported through the
cell membrane via simple diffusion include
organic molecules, such as benzene and
small uncharged molecules, such as H2O, O2,
N2, urea, glycerol,and CO2
27. Diffusion
Molecules are in continuous random motion
(Brownian motion)
Evident mostly in liquids and gases whose molecules
are free to move
Greater the concentration of molecules greater the
likelihood of collision and movement to chamber
with low concentration
28.
29. 1)The net movement of particles
2)from a region of higher concentration
3)to a region of lower concentration,
4)down the concentration gradient
. The energy that causes diffusion is the energy of the
normal kinetic motion of molecules
Diffusion
High concentration Low concentration
30. Diffusion can occurs either
through the lipid membrane or
through the carrier proteins
or through channel proteins
33. 1: SIMPLE DIFFUSION
Simple diffusion means the net
movement of molecules from higher
concentration to lower conc. through
“PROTEIN CHANNELS” or
“INTERCELLULAR SPACE” of cell
membrane without carrier proteins
and energy
34.
35. Diffusional equilibrium
Net movement ceases
when concentration of
particles is equal
everywhere within the
solution although
random movement of
the particles continues
38. Simple diffusion occur through
the cell membrane by two
pathways
1) lipid soluble substance through the interstices of
lipid bilayer
2) through channel proteins if water soluble and ion
and small
39.
40. A: SIMPLE DIFFUSION THROUGH LIPID BILAYER
CO2
O2
N2
Fatty acids
Alcohol
They all are lipid soluble (uncharged and also non
polar) and can diffuse through the membrane
41. TRANSPORT OF H2O
H2O passes through lipid bilayer because its size is
small and also thru aquaporins
42. SIMPLE DIFFUSION THROUGH PROTEIN CHANNEL
Larger water soluble substances and
charged particles (electrolytes)
passes through protein channels , not
through lipid bilayer.
43. Ion Channels
Ion channels are very specific with regards
to pore size and the charge on the molecule
to be moved
Move mainly Na, K, Cl and Ca
44. Reason of impermeability
of charge particles
They are hydrated ions so bigger size.
Outer pole of lipid bilayer have
negative charge………
46. Selective permeability of protein
channels
It may be due to :
Diameter of the channel
Its shape
Nature of electric charges
47. Gating of channels
Gating provides in controlling the ion permeability
of the channels
The opening and closing of gates are controlled in
two ways:
1) VOLTAGE GATING
2) LIGAND GATING
3) MECHANICAL GATING
48.
49. Voltage Gated channels in
Simple Diffusion:
Sodium Channels:
•0.3 by 0.5 nm in diameter
•Negatively charged on the inside
•Because of the negative charges they
pull the positively charged sodium ion
inside, away from the water molecule.
Potassium channel:
•0.3 by 0.3 nm in diameter
•No negative charge on the inside
•Pull the hydrated K ion inside. As no
negative charge on the inside of the
channel, no attractive forces for the
Na ion… also, Na ions hydrated form is
far too big….
53. Diffusion of low lipid soluble
substance and too large for channels
Like glucose pass thru the carrier
proteins
e.g. facilitated diffusion and active
transport
54. Factors affecting rate of simple
diffusion
1 Permeability of membrane
2 Concentration difference
3. Pressure difference
4 Electrical difference
5. Surface area of the membrane
6. molecular weight of the
substance
7. Thickness of the membrane
55. Factors that affect
the net rate of diffusion:
1. Concentration difference (Co-Ci)
net diffusion ∝ D (Co-Ci)
Figure 4-8; Guyton & Hall
56. The steeper the concentration gradient, the faster diffusion takes
place
Fast rate of
diffusion
Steeper concentration gradient
Concentration Gradient
Less steep concentration gradient
Slow rate of diffusion
58. 3. Pressure difference
• Higher pressure results in increased energy
available to cause net movement from high to low
pressure.
Figure 4-8; Guyton & Hall
66. 2: FACILITATED DIFFUSION
Definition: is the transport mechanism which require
“CARRIER PROTEIN”
Mechanism:
1. Molecule + CARRIER PROTEIN (loosely bound)
2. Conformational change in carrier protein
3. Molecule detached from carrier
4. No energy or ATP required
67.
68. FACILITATED DIFFUSION
Glucose
Amino acids
Other simple carbohydrates such as :
Galactose
Mannose
Arabinose
Xylose.
All require “carrier protein” for their transport, so
called “carrier mediated diffusion”
69.
70. Means by which glucose is transported into cells
muscles liver and RBCs
Insulin increases number of carriers for glucose in
plasma membrane of different cells
74. Saturation: A limited no. of
carrier binding sites are available
within a particular plasma membrane
for a specific substance. Thus, there is
a limit to the amount of substance a
carrier can transport across the
membrane in a given time. This is
called Transport Maximum (Tm).
75.
76. Mediated-Transport Systems
In simple diffusion,
flux rate is limited
only by the
concentration
gradient.
In carrier-
mediated
transport, the
number of
available carriers
places an
upper limit
on the flux rate.
80. How does water get through the HYDROPHOBIC Plasma
membrane?
Answer: Even though water is polar and so highly
insoluble in the membrane lipids, it readily passes
through the cell membrane thru 2 ways:
1.Water molecules are small enough to move
through the spaces created between the
phospholipid molecules’ tails
2.In many cells, membrane proteins form
aquaporins, which are channels specific for the
passage of water. About a billion water molecules
can pass in single file through an aquaporin channel
in one second. (renal tubules)
81. Osmosis
Definition:
The diffusion of water molecules
through a partially permeable membrane
from a solution of high water concentration
to a solution of lower water concentration
Down the concentration gradient
: sucrose
:water
molecules
Partially permeable
membrane
83. OSMOSIS
Diffusion of water through the semi permeable
membrane from a solution of higher water
concentration towards a solution of lower water
concentration
84. Partially-permeable
membrane
More free water molecules on this side
of membrane
Water-solute particle is too
large to pass through
membrane
Free water molecules diffuse in this direction
85. Osmosis: due to difference in
net hydrostatic pressure
The hydrostatic pressure of pure water is higher than that of
solution on right
86. As this column rises higher, it will
exert increasing pressure. At
some
point that hydrostatic pressure
will
reach an equilibrium, at which
point
no more net water will move across
the
semi-permeable membrane.
This pressure is the ‘osmotic
pressure’
of the starting solution on the
right.
87. Osmotic pressure
The amount of pressure required to stop further the
process of osmosis is called osmotic pressure Driving
force is the osmotic pressure caused by the
difference in water pressure
88. Osmotic pressure
The greater the solute conc. of a
solution, the greater its osmotic
pressure.
OR
The greater the no. of ion/molecule
when dissolved greater the osmotic
pressure.
89.
90. Example
Separate pure
water from a sugar
solution with semi
permeable
membrane
Both have same
hydrostatic pressure
Osmosis take water
from side 1 to side 2
because solution on
side 1 has more
hydrostatic pressure
91. Will all water go to side 2?
No it stops after some time. This is the
equilibrium state
92. As water moves by osmosis to
side 2.
Solution on side 2 has two
tendencies now
Tendency to push water back to
side 1 due to greater hydrostatic
pressure
Tendency to pull water by
osmosis back to side 2
Equilibrium is achieved when
tendency to pull water to side 1
and to push water into side 2
balances out
Equilibrium state
93. • Osmotic pressure depends on the number of
solutes/unit volume (rather than chemical nature of
solutes or mass of the particles)
94. REASON
Each particle in a solution regardless of its mass
exerts on average the same amount of pressure
against the membrane
K.E. = mv2
2
If more mass then less velocity and vice versa so KE on
average is same for both small and large particle
96. Solutes are dissolved particles in
solution (any type)
hypersmotic
(higher osmotic pressure)
hyposmotic
(lower osmotic pressure)
97. osmole
To express the concentration of a solution in terms of
no. of particles the unit osmole is used in place of
grams
1 osmole is 1 gram molecular weight of osmotically
active solute.
98. molarity - moles of solute / liters of solvent
(moles/liter = Molar)
mole - grams of substance = mol. wt. substance
l mole H = 1 gram H
1 mole C = 12 grams C
1 mole NaCl = 58 grams NaCl
1 mole C6H12O6 = 180 grams C6H12O6
58 grams NaCl/l liter water = 1 mole NaCl/liter = 1
Molar NaCl (lM NaCl)
180 g Glucose/1 liter water = 1 mole glucose/liter = 1
Molar glucose (1M Glucose)
99. Osmolarity/Osmolality
To describe the total number of osmotically
active particles per litre of solution term
osmolarity is used
IT IS OSMOLES PER LITER OF SOLUTION
The higher the osmolarity, the greater the
osmotic pressure of the solution.
100. Two solutions can have the same molarity but may have
different osmolarities. E.g.
OsM of 1 M glucose solution =1 OsM
OsM of 1 M NaCl solution = 2 OsM
101. The solution that has I osmole of solute dissolved in
each Kg of water have an osmolality of 1 osmole per
liter.
The solution that has 1/1000 osmoles dissolved per Kg
has an osmolality of I milliosmole
The normal osmolarity of ECF and ICF is 300mOsm
per Kg of water
102. Relation between osmolarity and molarity
mOsm (millisomolar) = index of the concn
or mOsm/L of particles per liter soln
mM (millimolar) = index of concn of
or mM/L molecules per liter soln
150 mM NaCl = 300 mOsm
300 mM glucose = 300 mOsm
103. Relation of osmolality to osmotic
pressure
At normal body temp. concentration of 1 osmole per
liter will cause osmotic pressure of 19300 mm Hg
osmotic pressure in the solution
1 milli osmole will be equivalent to 19.3mm Hg
osmotic pressure
Total osmotic pressure = 300 x 19.3 = 5790mmHg
We take 5500 0smotic pressure because many ions
in the body fluids are highly attracted to one another
and therefore can’t exert their full osmotic pressure
104. Tonicity is a relative term
Isotonic SolutionIsotonic Solution - both solutions have same
concentrations of solute
Hypotonic SolutionHypotonic Solution - One solution has a lower
concentration of solute than another.
Hypertonic SolutionHypertonic Solution - one solution has a
higher concentration of solute than another.
105. Hypotonic – The solution on one side of a membrane where the solute
concentration is less than on the other side. Hypotonic Solutions contain a low
concentration of solute relative to another solution.
Hypertonic – The solution on one side of a membrane where the solute
concentration is greater than on the other side. Hypertonic Solutions contain a
high concentration of solute relative to another solution.
106. RED CELL IN ISOTONIC
SOLUTION
Cytoplasm and
solution outside the
cell has same
concentration of
solutes so no net
movement of water so
cell maintain its
shape
107. Red blood cell in
Low water potential 1. Cytoplasm has higher
water potential
compared to the
solution outside the
cell.
2. Water leaves by
osmosis
3. Cell shrinks and little
spikes appear on cell
surface membrane.
(Crenation)
108. Red blood cell in
High water potential 1. Cytoplasm has lower
water potential
compared to solution
outside cell
2. Water enters by
osmosis
3. Animal cell will swell
and may bursts as it
does not have a cell
wall to protect it.
109. Special categories of transport
1. BULK TRANSPORT:
It is the transport mechanism in
which large quantity of substances
transported from high pressure to
low pressure e.g. exchange thru
capillary membrane
110. Membrane Transport
Vesicular transport
Material is moved into or out of the cell wrapped in
membrane
Active method of membrane transport
Two types of vesicular transport
Endocytosis
Process by which substances move into cell
Pinocytosis – nonselective uptake of ECF
Phagocytosis – selective uptake of multimolecular particle
Exocytosis
Provides mechanism for secreting large polar molecules
111. Transport in Vesicles
Requires energy (ATP)
Involves small membrane sac
Endocytosis: importing materials into cell
Phagocytosis: ingestion of particles such as bacteria
into white blood cells (WBCs)
Pinocytosis: ingestion of fluid
Exocytosis: exporting materials
111
113. ENDOCYTOSIS
Large molecule or macromolecules transported by
endocytosis.
Endocytosis are of 3 types
a. Pinocytosis
b. Phagocytosis
c. Receptor mediated endocytosis
114. PINOCYTOSIS (Cell drinking)
1. non selective uptake of particle( in the form of
droplet fluid ECF) bind with outer surface of
membrane.
2 Cell membrane evaginate around the
droplets
3 It is detached from cell membrane forms
ENDOSOME.
115. PINOCYTOSIS (Cell drinking) Cont..
4. Primary lysosomse attach with edosome
,converted into secondry lysosomes.
5. Hydrolytic enzymes present in secondary
lysosome becomes activated and digest the
content of endosome
122. ACTIVE TRANSPORT
Definition:
Active transport is a carrier-mediated transport wherein
molecules and ions are moved against their concentration
gradient across a membrane and requires expenditure of
energy.
Active transport is divided into 2 types according to the
source of the energy used.
124. In both instances, transport depends on
carrier proteins. , the carrier protein functions
differently from the carrier in facilitated diffusion
because it is capable of imparting energy to the
transported substance to move it against the
electrochemical gradient by acting as an enzyme
and breaking down the ATP itself.
125. Primary Active Transport
• The primary active transport carriers are termed as pumps.
•molecules are “pumped” against a concentration
gradient at the expense of energy (ATP)
– direct use of energy
Secondary Active Transport
• transport is driven by the energy stored in the
concentration gradient of another molecule (Na+
)
– indirect use of energy
126. Types of Active Transport:
In primary active transport, the energy is derived
directly from breakdown of adenosine triphosphate
(ATP) or from some other high-energy phosphate
compound.
In secondary active transport, the energy is derived
secondarily from energy stored in the form of an ion
concentration gradient between the two sides of a cell
membrane, created originally by primary active
transport. Thus, energy is used but it is “secondhand”
energy and NOT directly derived from ATP.
127. Primary Active Transport
In primary active transport, energy in the form of ATP is
required to change the affinity of the carrier protein binding
site when it is exposed on opposite sides of plasma membrane.
The carrier protein also acts as an enzyme that has ATPase
activity, which means it splits the terminal phosphate from an
ATP molecule to yield ADP and inorganic phosphate plus free
energy.
Examples:
1. Sodium-Potassium Pump (every cell).
2. Hydrogen pump: occurs at 2 places in the human body:
- in the gastric glands of the stomach
- In the kidneys
3. Ca pump (muscles)
128. Na-K PUMP:
• It has the following
structure:
1. 3 receptor sites for
binding Na ions on the
portion of the protein
that protrudes to the
inside of the cell.
2. 2 receptor sites for
potassium ions on the
outside.
3. The inside portion of this
protein near the sodium
binding site has ATPase
activity.
130. Na+
-K+
Pump
Moves K+
while moving Na+
Works constantly to maintain [Na+
] inside the cell – Na+
comes in thru other channels or carriers
131. FUNCTIONS OF SODIUM-POTASSIUM PUMP:
1. Control the Volume of each cell: It helps regulate cell
volume by controlling the concentrations of solutes
inside the cell and thus minimizing osmotic effect that
would induce swelling or shrinking of the cell. If the
pump stops, the increased Na concentrations within the
cell will promote the osmotic inflow of water, damaging
the cells.
2. Electrogenic nature of the pump: It establishes Na and
K concentration gradients across the plasma membrane
of all cells; these gradients are critically important in the
ability of nerve and muscle cells to generate electrical
signals essential to their functioning.
3. Energy used for Secondary active transport: The steep
Na gradient is used to provide energy for secondary
active transport.
132. 2. Ca2+
ATPase
• present on the cell membrane and the sarcoplasmic
reticulum
• maintains a low cytosolic Ca2+
concentration
133. • found in parietal cells of gastric glands (HCl secretion)
and intercalated cells of renal tubules (controls blood
pH)
134. Examples of Primary Active Transport Pumps:
1) Na+
/K+
-ATPase pump
- found in the plasma membrane
- 3 Na+
are pumped out of cytosol and 2 K+
are pumped into the cytosol
2) Ca+2
-ATPase pump
- found in the plasma membrane, & endoplasmic reticulum membranes
- pumps Ca+2
out of cytosol and either into the ER or the extracellular fluid
3) H+
-ATPase
- found in the plasma membrane, lysosomes, & mitochondria inner
membrane
- pumps H+
out of the cell and into extracellular fluid
- pumps H+
into lysosomes to be used as digestive enzymes
- used in the electron transport chain of mitochondria
4) H+
/K+
-ATPase
- used in acid secreting cells of the kidneys and stomach
- pumps one H+
out of cell and one K+
into the cell
135. Saturation
• similar to facilitated diffusion
• rate limited by Vmax of the transporters
Energetics
• up to 90% of cell energy expended for active
transport!
Competition
Specificity
136. Secondary Active Transport
1. Co-transport (co-porters): substance is
transported in the same direction as the “driver” ion (Na+
)
Examples:
inside
outside
Na+
AA Na+ gluc 2 HCO3
-Na+
- co-transport and counter-transport -
137. 2. Counter-transport (anti-porters): substance is
transported in the opposite direction as the “driver” ion (Na+
)
Examples:
Na+
Ca2+
Na+
H+
Cl-
/H+
Na+
/HCO3
-
outside
inside
138.
139. SECONDARY ACTIVE
TRANSPORT
CO-TRANSPORT
Symport
Na moves downhill
Molecule to be co-
transported moved in the
same direction as Na, i.e. to
the inside of the cell.
E.g. Na with glucose and
amino acids.
Site: intestinal lumen and
renal tubules of kidney.
COUNTER TRANSPORT
Anti-port
Na moves downhill
Molecule to be counter-
transported moves in the
opposite direction to Na, i.e. to
the outside of the cell.
E.g. Na with Calcium and
Hydrogen ions.
Site: Na-Ca counter transport in
almost all cells of the body and
Na-H+
in the proximal tubules of
the kidney.
140. Types of Secondary Transporters
Symporters (two solutes move(two solutes move
in same direction) Lac-in same direction) Lac-
permease, Napermease, Na++
/glucose/glucose
transporter)transporter)
AntiportersAntiporters (two solutes move(two solutes move
in opposite directionsin opposite directions
NaNa++
/Ca/Ca2+2+
exchanger)exchanger)
UniportersUniporters (mitochondrial Ca(mitochondrial Ca2+2+
uniporter and NHuniporter and NH++
44-transporter-transporter
in plants require Hin plants require H++
gradient)gradient)
141. Transcellular Transport of Glucose / AA
Na+
glucose
AA
Na+
low high
epitheliumlumen
extracellular
fluid
Na+
Na+
K+
K+
AAAA
glucoseglucose
low
142. Diffusion Active Transport
• occurs down a concn.
gradient
• no mediator or involves
a “channel” or “carrier”
• no additional energy
• occurs against a concn.
gradient
• involves a “carrier”
• requires ENERGY
Figure 4-2; Guyton & Hall
Uncharged or nonpolar molecules (such as O2, CO2, and fatty acids) are highly lipid soluble and readily permeate the membrane. Charged particles (ions such as Na and K) and polar molecules (such as glucose and proteins) have low lipid solubility but are very soluble in water. The lipid bilayer serves as an impermeable barrier to particles poorly soluble in lipid.
What u see is the motion that all molecules present in the body are undergoing…. Only at absolute zero does the motion stop. Molecule A will collide with Molecule B … It will slow down a little while Molecule B will accelerate a little… and so on… This will go on till they spread out gradually and are evenly distributed. Now, equilibrium has occurred and diffusion stops. The molecules are still in motion but the concentration has equalized everywhere…. This is called dynamic equilibrium.
A good example is a drop of blue ink being dropped into a beaker containing water. The way the blue ink spreads till it evenly spreads out is called diffusion…..
Another good example is open bottle of cologne in a room… the cologne spreads out in the room, u can smell it after a while even at the other end of the room.
Occurs at capillary membrane. Higher pressure in the capillary facilitates the diffusion of molecules into the tissues.
Pressure actually means the sum of all the forces of the different molecules striking a unit area of membrane at a given instant.
Facilitated Diffusion….
Figure 3.9: Relationship between solute and water concentration in a solution.
(a) Pure water. (b) Solution.
To put the pump in perspective: when 2 potassium ions bind on the outside of the carrier protein and three sodium ions bind on the inside, the ATPase
function of the protein becomes activated. This then cleaves one molecule of ATP, splitting it to adenosine diphosphate (ADP) and liberating a high-energy
phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the three sodium ions to the outside and the two potassium ions to the inside.
