lecture on membrane transport by dr. mudassar ali roomi

7/30/2019 lecture on Membrane Transport by Dr. Mudassar Ali Roomi.

1/37

Membrane Transport

By

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


2/37

Extracellular & Intracellular fluid

composition is different!!

ECF Vs ICF

Na+ > Na+

K+ < K+

Cl- > Cl-PO4

--- < PO4---

Proteins < Proteins

Transport mechanisms are responsible for Differentialcomposition of ECF & ICF.


3/37

ECF & ICF composition is

different!!


4/37

Lipid barrier of cell membrane &

Cell membrane transport proteins:


5/37

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 Transport1. Secondary Active Co-transport

2. Secondary Active Counter-transport

Endocytosis1. Pinocytosis

2. Phagocytosis

Exocytosis


6/37

What is the Composition of cell

membrane??

Lipid bilayer.

Large no. of protein molecules in the lipid(including many penetrating proteins).


7/37

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.


8/37

Penetrating proteins

as

transport proteins:

Channel proteins:

Have watery spaces thatpenetrate throughout themolecule.

Allow free movement ofwater, selected ions ormolecules.

Highly selective.

Carrier proteins:

Bind with molecules orions to be transported.

Undergo conformationalchange.

Leading to movement ofsubstances through the

interstices of protein toother side of membrane.


9/37

Types of Passive transport:

1. Simple diffusion.

2. Facilitated diffusion.

3. Osmosis.


10/37

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 useof energy is called

diffusion.


11/37

Simple Vs

Facilitated

Diffusion:

SIMPLE DIFFUSION

Movement of highlypermeable moleculefrom region of highconcentration to lowerconc. Without the help

of carrier protein andwithout use of energy.

Example: transport ofO2 and CO2 across

the membrane.

FACILITATED DIFFUSION

Movement of substancesacross the cell membrane incombination with carrierprotein towards concentrationgradient without utilization of

energy. Example: glucose transport

through the GLUTtransporters.


12/37

Some important definitions

OSMOLE:

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

called one osmole.

1 osmole = 6.02 x 1023

particles. OSMOLALITY:

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

osmolality

OSMOLARITY: Osmole per liter of solution.

In usual practice.


13/37

OSMOSIS across selectively permeablemembrane- net diffusion of water:

Process of net

movement of water

across a selectively

permeablemembrane, caused

by a concentration

difference of water is

called osmosis.


14/37

Osmotic Pressure:

Definition: The exactamount of pressurerequired to stop osmosisis called Osmotic

Pressure. Osmotic pressure is

directly proportional to thenumber of osmoticallyactive particles. **


15/37

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 mv2

2

K.E = average kinetic energy, v = velocity, m =

mass.

If mass is less, velocity is more.


16/37

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 (Nernstpotential)


17/37

Effect of conc. difference on net

diffusion through a membrane:

The rate at which the substance diffuses inward is directlyproportional to the concentration difference of molecules across themembrane


18/37

Effect of membrane electrical potential on

diffusion of ions-

the Nernst Potential Electrical potential if applied across the

membrane Electrical charges ofions cause them to move through themembrane, even in the absence ofconcentration difference.

Conc. difference of ions develops in

the direction opposite to electricalpotential difference.

Ions keep moving until the 2 effectsbalance each other.

Definition: At normal body

temperature, the electrical differencethat will balance a given conc.difference of univalent ions is called asNernst potential or equilibriumpotential.

EMF (mV) = +/- 61 log C1C2


19/37

Effect of pressure difference across

the membrane:

Pressure inside the bloodcapillary is about 20 mmHggreater than outside.

So, at arterial end of the

capillary fluid is filtered out.


20/37

Diffusion through the cell membrane:

Simple diffusion & Facilitated diffusion

Simple diffusion

Kinetic movement of

ions / molecules

through a membraneopening /

intermolecular spaces

without any

interaction with carrierproteins in the

membrane.

Facilitated diffusion

Requires interaction of acarrier protein.

Carrier protein binds

chemically with & shuttlesions / molecules through themembrane.


21/37

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 largetransport proteins.


22/37

Diffusion of lipid-soluble substances

through the lipid bilayer

The main factor effecting the rate ofdiffusion through lipid bilayer is lipidsolubility of the substance.

Examples of highly lipid solublesubstances:

1. Oxygen,

2. nitrogen,

3. carbondioxide,

4. alcohol.


23/37

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).


24/37

Diffusion through Protein Channels

& Gating of these channels:

Tubular pathways from ECF to ICF.

Simple diffusion from one side ofmembrane to other across protein

channels.


25/37

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).


26/37

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


27/37

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, pullingsodium ions away from hydrating watermolecules.

Once in the channel, sodium ions diffuse ineither direction, according to laws of diffusion(down the concentration gradient)


28/37


29/37

Selective permeability of protein

channels for potassium ions:Potassium channels:

Slightly smaller channels.

Not negatively charged.

Chemical bonds are different. Nostrong attractive forces pullsodium ions away from watermolecules that hydrate them.

Hydrated form of potassium ion is

smaller, which can pass easilythrough small potassium channel.

Sodium channels:

Slightly bigger channels.

Negatively charged on inside.

Chemical bonds are different. Strongattractive forces pull sodium ionsaway from water molecules thathydrate them.

Hydrated form of sodium ion is

bigger, as sodium ion attracts morewater molecules. They cannot passthrough small potassium channel,resulting into selective permeabilityfor a specific ion.


30/37

Gating of protein channels

Significance:

Selective gating of sodium& potassium ionsControl of ion

permeability of thechannels.

Mechanism:

Some gates are extensionsof transport proteinmolecule open andclose by conformationalchange


31/37

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.


32/37

Voltage & Ligand gating

Voltage gated:

When strong negative chargeinside the cell membrane (atRMP):

Sodium gates remain closed.

When inside of membrane losesits negative charge:

Sudden opening of sodiumgates massive sodium influx onset of action potential.

When inside becomes positive: Potassium gates open

potassium efflux terminationof action potential.

Chemical / Ligand gated:

Example:

Effect of Acetylcholine onacetylcholine channel gate

opens (negatively chargedpore of 0.65 nm diameter)passage of unchargedmolecules / positive ionssmaller than 0.65 nm.

Important at:

Nerve to nerve junction &

Nerve to Muscle junction


33/37

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 acrossthe 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 phosphorylationleading to opening and closing of these channels.

STRETCH OR PRESSURE GATED CHANNELS

Mechanical stretch of membrane results in channel opening.


34/37

Facilitated Diffusion:

Carrier mediated diffusion.

Carrier facilitates diffusion of thesubstance 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.


35/37

Facilitated diffusion Vs Simple diffusion:

Facilitated diffusion

Rate of diffusion reaches

a maximum (Vmax

), 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).


36/37

What limits the rate of

facilitated diffusion: 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.


37/37

Primary Active Transport:

Sodium-potassium pump: The sodium potassium pump is a

complex of two separate globularproteins.

Smaller protein might anchor theprotein complex in the lipid membrane

The larger protein has three specific

features that are important for thefunctioning of the pump:

1. It has three receptor sites for bindingsodium ionson the portion of theprotein that protrudes to theinside ofthe cell.

2. It has two receptor sites for potassiumionson the outside.

3. The inside portion of this protein nearthe sodium binding sites has ATPaseactivity.

lecture on membrane transport by dr. mudassar ali roomi

Documents