118785130 lecture on membrane transport by dr mudassar ali roomi

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    Membrane Transport

    By

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

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    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.

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    ECF & ICF composition is

    different!!

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    Lipid barrier of cell membrane &

    Cell membrane transport proteins:

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    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

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    What is the Composition of cell

    membrane??

    Lipid bilayer.

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

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    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.

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    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.

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    Types of Passive transport:

    1. Simple diffusion.

    2. Facilitated diffusion.

    3. Osmosis.

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    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.

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    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.

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    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.

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    Osmotic Pressure:

    Definition: The exactamount of pressurerequired to stop osmosisis called Osmotic

    Pressure. Osmotic pressure is

    directly proportional to thenumber of osmoticallyactive particles. **

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    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)

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    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

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    Effect of membrane electrical potential on

    diffusion of ions-

    the Nernst Potential Electrical potential if applied across the

    membraneElectrical 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

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    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.

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    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 a

    carrier protein.

    Carrier protein binds

    chemically with & shuttlesions / molecules through the

    membrane.

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    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.

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    Diffusion of lipid-soluble substances

    through the lipid bilayer

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

    Examplesof highly lipid solublesubstances:

    1. Oxygen,

    2. nitrogen,

    3. carbondioxide,

    4. alcohol.

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    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).

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    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.

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    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).

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    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

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    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)

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    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.

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    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

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    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 sodiumgatesmassive sodium influxonset of action potential.

    When inside becomes positive: Potassium gates open

    potassium effluxterminationof action potential.

    Chemical / Ligand gated:

    Example:

    Effect of Acetylcholine onacetylcholine channelgate

    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

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    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.

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    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.

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    Facilitated diffusionVs 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).

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    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.

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    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 ions on the portion of theprotein that protrudes to theinside ofthe cell.

    2. It has two receptor sites for potassiumions on the outside.

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