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Membrane Transport

By

Dr. Mudassar Ali Roomi (M.B; B.S., M. Phil.)

Extracellular & Intracellular fluid

composition is different!!

ECF

Vs

Na +

>

K +

<

Cl -

>

PO 4 ---

<

Proteins <

ICF

Na

+

K + Cl - PO 4 Proteins

---

Transport mechanisms are responsible for Differential composition of ECF & ICF.

ECF & ICF composition is different!!

ECF & ICF composition is different!!

Lipid barrier of cell membrane &

Cell membrane transport proteins:

Lipid barrier of cell membrane & Cell membrane transport proteins:

Different types of transport across

a selectively permeable membrane:

Diffusion or passive transport:

1.

Simple Diffusion

2.

Facilitated Diffusion

3.

Osmosis

Active transport

Primary Active Transport

Secondary Active Transport

1. Secondary Active Co-transport

2. Secondary Active Counter-transport

Endocytosis

1.

Pinocytosis

2.

Phagocytosis

Exocytosis

What is the Composition of cell

membrane??

Lipid bilayer.

Large no. of protein molecules in the lipid

(including many penetrating proteins).

Lipid bilayer as barrier against

water molecules & water-soluble substances:

Lipid barrier is not miscible with ECF or ICF.

Allows lipid soluble substances to penetrate directly through the lipid substance.

is not miscible with ECF or ICF. • Allows lipid soluble substances to penetrate directly through

Penetrating proteins as transport proteins:

Channel proteins:

Have watery spaces that penetrate throughout the molecule.

Allow free movement of water, selected ions or molecules.

Highly selective.

of water, selected ions or molecules. • Highly selective. Carrier proteins: • Bind with molecules or

Carrier proteins:

Bind with molecules or

ions to be transported.

Undergo conformational

change.

Leading to movement of substances through the

interstices of protein to

other side of membrane.

Types of Passive transport:

1. Simple diffusion.

2. Facilitated diffusion.

3. Osmosis.

DIFFUSION

Movement of substances

down the conc. gradient either through opening in

cell membrane or in

combination with carrier

protein, caused by simple kinetic motion of molecules without the use

of energy is called

diffusion.

with carrier protein, caused by simple kinetic motion of molecules without the use of energy is

Simple Vs Facilitated

Diffusion:

SIMPLE DIFFUSION

Movement of highly

permeable molecule

from region of high

concentration to lower conc. Without the help

of carrier protein and

without use of energy.

Example: transport of O2 and CO2 across the membrane.

• Example : transport of O2 and CO2 across the membrane. FACILITATED DIFFUSION • Movement of

FACILITATED DIFFUSION

Movement of substances

across the cell membrane in

combination with carrier protein towards concentration

gradient without utilization of

energy.

Example: glucose transport through the GLUT transporters.

Some important definitions

OSMOLE:

No. of particles in one mole of un-dissociated solute is

called one osmole.

1 osmole = 6.02 x 10 23 particles.

OSMOLALITY:

No. of osmole of solute per kg of water is called osmolality

OSMOLARITY:

Osmole per liter of solution.

In usual practice.

OSMOSIS across selectively permeable

membrane- “net diffusion” of water:

Process of net

movement of water

across a selectively permeable

membrane, caused

by a concentration difference of water is called osmosis.

of water across a selectively permeable membrane, caused by a concentration difference of water is called

Osmotic Pressure:

Definition: The exact

amount of pressure

required to stop osmosis is called Osmotic Pressure.

Osmotic pressure is directly proportional to the number of osmotically active particles. **

called Osmotic Pressure. • Osmotic pressure is directly proportional to the number of osmotically active particles.

Importance of number of osmotic particles (molar conc.) in determining osmotic pressure:

Each particle in a solution, regardless of its

mass, exerts on average the same amount of pressure against the membrane.

K.E = 1 mv 2

2

K.E = average kinetic energy, v = velocity, m = mass. If mass is less, velocity is more.

Factors affecting rate of diffusion across a

selectively permeable membrane:

1.

Effect of conc. difference across membrane

2.

Velocity of kinetic motion.

3.

Effect of temperature

4.

No. & size of openings (channels) in the membrane.

5.

Lipid solubility of the substance.

6.

Water solubility of the substance.

7.

Size of molecules.

8.

Selective permeability of protein channels.

9.

Opening or closing of many protein channels by gates.

10.

Effect of pressure difference across membrane

11.

Effect of membrane electrical potential (Nernst potential)

Effect of conc. difference on net

diffusion through a membrane:

The rate at which the substance diffuses inward is directly proportional to the concentration difference of molecules across the membrane

the substance diffuses inward is directly proportional to the concentration difference of molecules across the membrane

Effect of membrane electrical potential on

diffusion of ions-

the “Nernst Potential”

Electrical potential if applied across the membrane Electrical charges of

ions cause them to move through the

membrane, even in the absence of concentration difference.

Conc. difference of ions develops in the direction opposite to electrical potential difference.

Ions keep moving until the 2 effects balance each other.

Definition: At normal body

temperature, the electrical difference

that will balance a given conc.

difference of univalent ions is called as Nernst potential or equilibrium potential.

EMF (mV) = +/- 61 log C 1

C 2

of univalent ions is called as Nernst potential or equilibrium potential. • EMF (mV) = +/-

Effect of pressure difference across

the membrane:

Pressure inside the blood capillary is about 20 mmHg greater than outside.

So, at arterial end of the capillary fluid is filtered out.

blood capillary is about 20 mmHg greater than outside. • So, at arterial end of the

Diffusion through the cell membrane:

Simple diffusion & Facilitated diffusion

Simple diffusion

Kinetic movement of

ions / molecules through a membrane

opening /

intermolecular spaces without any interaction with carrier

proteins in the membrane.

Facilitated diffusion

Requires interaction of a carrier protein.

Carrier protein binds chemically with & shuttles ions / molecules through the membrane.

of a carrier protein. • Carrier protein binds chemically with & shuttles ions / molecules through

2 pathways for simple diffusion:

Through interstices of

lipid bilayer if diffusing

substance is lipid soluble.

Through watery

channels that

penetrate all the way through large

transport proteins.

substance is lipid soluble. • Through watery channels that penetrate all the way through large transport

Diffusion of lipid-soluble substances

through the lipid bilayer

The main factor effecting the rate of

diffusion through lipid bilayer is lipid

solubility of the substance.

Examples of highly lipid soluble

substances:

1. Oxygen,

2. nitrogen,

3. carbondioxide,

4. alcohol.

of the substance. • Examples of highly lipid soluble substances: 1. Oxygen, 2. nitrogen, 3. carbondioxide,

Diffusion of water & other lipid-insoluble

molecules through protein channels:

Rapid penetration

through protein

channels:

e.g., Water &

other lipid-insoluble

(water-soluble & small molecules).

Slow penetration:

Water-soluble larger

molecules. e.g., urea molecule

(size is 20 % > water;

penetration is 1000 x < water).

Water-soluble larger molecules. e.g., urea molecule (size is 20 % > water; penetration is 1000 x

Diffusion through Protein Channels

& Gating of these channels:

Tubular pathways from ECF to ICF.

Simple diffusion from one side of

membrane to other across protein

channels.

• Tubular pathways from ECF to ICF. • Simple diffusion from one side of membrane to

two important characteristics of

protein channels:

1.

Often show selective

permeability for one

or more specific ions or molecules.

2.

Most channels are

gated (can be opened or closed by gates).

for one or more specific ions or molecules. 2. Most channels are gated (can be opened

Specificity of protein channels:

It is due to certain characteristics which are :

1. Channel diameter

2. Shape of the channel

3. Nature of electrical charges

4. Chemical bonds along their inner surfaces

Characteristics of sodium-channel:

(specific for sodium ion passage)

0.3 to 0.5 nm diameter.

Strong Negative charge on inside.

Pull small dehydrated sodium ions inside, pulling sodium ions away from hydrating water molecules.

Once in the channel, sodium ions diffuse in

either direction, according to laws of diffusion (down the concentration gradient)

Selective permeability of protein

channels for potassium ions:

Potassium channels:

Slightly smaller channels.

Not negatively charged.

Chemical bonds are different. No

strong attractive forces pull

sodium ions away from water molecules that hydrate them.

Hydrated form of potassium ion is smaller, which can pass easily

through small potassium channel.

Sodium channels:

Slightly bigger channels.

Negatively charged on inside.

Chemical bonds are different. Strong

attractive forces pull sodium ions

away from water molecules that hydrate them.

Hydrated form of sodium ion is

bigger, as sodium ion attracts more

water molecules. They cannot pass

through small potassium channel, resulting into selective permeability for a specific ion.

Gating of protein channels

Significance:

Selective gating of sodium

& potassium ions Control of ion

permeability of the

channels.

Mechanism:

Some gates are extensions

of transport protein

molecule open and close by conformational change

channels. Mechanism: Some gates are extensions of transport protein molecule  open and close by conformational

2 principal ways of opening & closing of gates:

Voltage & Ligand gating

Voltage gating:

Molecular conformation of the gate or Molecular conformation of the chemical bonds respond to electrical potential across cell

membrane.

Chemical (ligand) gating:

Gates open by binding of

a chemical substance (ligand) with the protein channel

conformational or

chemical bonding change in protein molecule that opens / closes the gate.

Voltage & Ligand gating

Voltage gated:

When strong negative charge inside the cell membrane (at RMP):

Sodium gates remain closed.

When inside of membrane loses

its negative charge:

Sudden opening of sodium gates massive sodium influx onset of action potential. When inside becomes positive:

Potassium gates open

potassium efflux termination of action potential.

Chemical / Ligand gated:

Example:

Effect of Acetylcholine on acetylcholine channel gate opens (negatively charged

pore of 0.65 nm diameter)

passage of uncharged molecules / positive ions smaller than 0.65 nm.

Important at:

Nerve to nerve junction &

Nerve to Muscle junction

4 types of gated channels:

LIGAND GATED

Some protein channel gates are opened by the binding of a

chemical substance with them.

e.g acetylcholine channels.

VOLTAGE GATED.

Some protein channel gates respond to electrical changes across

the cell membrane. e.g. sodium potassium channels.

PHOSPHORYLATED GATED CHANNELS

When ATP is broken down to ADP a phosphate group is released which attaches to the protein channel causing its phosphorylation

leading to opening and closing of these channels.

STRETCH OR PRESSURE GATED CHANNELS

Mechanical stretch of membrane results in channel opening.

Facilitated Diffusion:

Carrier mediated diffusion.

Carrier facilitates diffusion of the

substance to the other side. Examples:

Glucose & most Amino Acids. In presence of insulin, glucose transport increases 10-20-fold.

Glucose carrying protein has molecular weight of 45,000.

Facilitated diffusion Vs Simple diffusion:

Facilitated diffusion

Rate of diffusion reaches a maximum (V max ), as the concentration of diffusing substance increases & cannot rise greater than V max

Simple diffusion

Rate of diffusion varies directly with concentration of diffusing substance (if the channel is open).

Saturation of carrier

molecules.

The rate of transport cannot be greater than the rate at

which carrier protein

molecule can undergo change back & forth between its 2 states.

protein molecule can undergo change back & forth between its 2 states. What limits the rate

What limits the rate of

facilitated diffusion:

protein molecule can undergo change back & forth between its 2 states. What limits the rate

1.

2.

3.

Primary Active Transport:

Sodium-potassium pump:

The sodium potassium pump is a complex of two separate globular proteins.

pump is a complex of two separate globular proteins. Smaller protein might anchor the protein complex

Smaller protein might anchor the protein complex in the lipid membrane

The larger protein has three specific features that are important for the functioning of the pump:

It has three receptor sites for binding sodium ions on the portion of the protein that protrudes to the inside of the cell.

It has two receptor sites for potassium

ions on the outside.

The inside portion of this protein near the sodium binding sites has ATPase activity.