Transport Across Cell Memberane

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TRANSPORT ACROSS CELL

MEMBRANE

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TRANSPORT ACROSS CELL MEMBRANE

• Based on the usage of carrier


• Carrier mediated
• E.g. Facilitated Diffusion, Active transport
• Non Carrier mediated
• E.g. Osmosis, Diffusion
• Based on their energy requirements
• Passive transport, Active transport

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TRANSPORT ACROSS CELL MEMBRANE

• Diffusion
• Osmosis
• Active transport
• Endocytosis &
• Exocytosis

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DIFFUSION

• Is a passive process
• No external source of energy is needed
• Molecules move from areas of higher concentration to
areas of lower concentration (Down their chemical
gradient)
• Cations move to negatively charged areas and vice
versa (Down their electrical gradient)

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SIMPLE DIFFUSION

• Kinetic movement of molecules / ions occurring


through a membrane opening or through
intermolecular spaces without interaction with
carrier protein in the membrane

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DIFFUSION
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• The Rate of diffusion is given by Fick’s law of diffusion
Rate of diffusion (Flux) = A * D * (C1-C2)/T
A= Area of the membrane
C1-C2= Concentration difference / gradient
T= Thickness of the membrane
D= Diffusion coefficient = Solubility / √Molecular
weight

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• Thickness / distance - Greater the distance / thickness,
lesser is the diffusion
• Gradient - Larger the gradient faster the diffusion
• Temperature - Higher the Temp. faster the diffusion
• Molecular Weight - Increase in Molecular Weight
decreases diffusion

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• Area- Larger the area greater is the diffusion
• Solubility- Greater the solubility greater is the diffusion
• Lipid soluble substances diffuse through lipid bi layer of
the membrane e.g. O2, CO2 etc
• Rate Of diffusion depends on the lipid solubility
• Water & other Lipid insoluble substances diffuse through
channels in Protein molecules that penetrate all the way
through the membrane

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CLINICAL APPLICATION (DIFFUSION)

• Applied in the Dialysis procedure for the treatment of


renal failure
• A solution with no waste products & with electrolyte
concentration appropriately adjusted is separated from
the patient’s blood by a dialyzing membrane.
• The process of diffusion tends to normalize the
patient’s blood

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• Protein channels: Extend from the extra cellular to the
intracellular fluid through the membrane

• The characteristic features are


a. Selective permeability to certain substances
b. Many of the channels can be opened/closed by
gates

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SELECTIVE PERMEABILITY

Many of the protein channels are highly selective for


transport of one or more of specific ions or molecules
e.g. Na, K channels

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GATING

Provides a means of controlling the ion permeability of


the channels.
• Voltage gating : Opening or closing is controlled by
electrical potential across the cell membrane
• Chemical/ Ligand gating : Gates are controlled by the
binding of a chemical substance (a ligand) with the
protein e.g. Ach

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GATED CHANNEL
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FACILITATED DIFFUSION

• Diffusion facilitated by the carrier


• Is a type of passive transport
• No external energy is needed
• Also called carrier mediated diffusion
• The carrier protein undergoes repetitive structural
changes during which the binding sites for the substance
is alternatively exposed to ICF & ECF
• The substance is likely to bind to the carrier where it is
more highly concentrated & dissociate from the carrier
where it is less highly concentrated.
- E.g. Glucose transport into RBCs, muscle and adipose
tissue (when insulin is present)

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Differs from Simple diffusion in the following ways :
•Saturation :Rate of diffusion increase with increase
in concentration gradient to reach a plateau when all
the binding sites on the carrier proteins are filled.
•Specificity : Carrier proteins are highly specific for
different molecules
•Competition: Molecules of similar structure compete
for the carrier site

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Facilitated Diffusion

Rate of Diffusion

Simple Diffusion

Concentration gradient

FACILITATED DIFFUSION
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FACILITATED DIFFUSION
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NON IONIC DIFFUSION
• Some weak acids & bases are soluble in cell membrane in
the un-dissociated form, whereas they cross membrane
with difficulty in ionic form.
• So if molecules of un-dissociated substance diffuse from
one side of membrane to the other & then dissociate
there is net movement of the un-dissociated substance
from one side of the membrane to another
E.g. In kidneys
The secretion of Ammonia (NH3) from the renal tubular
cell to the filtrate (tubular lumen) where it is changed to
NH4 thus maintaining the concentration gradient for
diffusion of NH3.
Salicylate & a number of drugs that are weak bases or
acids are secreted by nonionic diffusion.
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OSMOSIS

• Is a passive flow of water (solvent) across a


selectively permeable membrane in to a region of
higher solute concentration to which the membrane
is impermeable.

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OSMOTIC PRESSURE

• Is the pressure which when applied to the side of


higher solute concentration prevents osmosis
• Depends on the no. of particles dissolved in
solution & not on size & Mol.Wt
• Concentration of the solution in terms of no. of
osmotically active particles is expressed in terms
of osmoles or milliosmoles (instead of grams)

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OSMOTIC PRESSURE

• One Osmole is one gram Mol.wt of osmotically active


substance (solute)
• e.g. 1gm Mol.wt of glucose(180gms) is equal to 1 osmole
because glucose does not dissociate.
• If dissociates eg 1gram Mol.wt of NaCl (58.5grams) is
equal to 2 Osmole

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• Solution having 1 osmole of solute dissolved in each kg of
water is said to have an osmolality of 1 osmole per kg
• The osmotic pressure exerted by the colloids is called
colloidal osmotic pressure (retention of fluid within the
vascular system)
• The colloidal osmotic pressure by the plasma proteins is
called oncotic pressure (25mmHg)

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• Osmolality : Refers to the number of osmotically
active particles (osmoles) per Kg of solvent
• Normal plasma osmolality 290mOsm/Kg of water
(by Na Cl,HCO3,glucose urea & Plasma Proteins)
• Osmolarity : refers to number of osmoles per Litre
of solution

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TONICITY OF FLUIDS

• The osmolality of a solution relative to plasma is


called Tonicity.
• Solution having the same osmolality as plasma –
Isotonic (0.9% Nacl,5% Glucose)
• Those with greater osmolality-hypertonic
• Those with lesser osmolality -hypotonic

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CLINICAL IMPORTANCE

• Plasma osmolality is important in assessing


dehydration, over hydration & other fluid &
electrolyte abnormalities
E.g. Plasma osmolality increase in dehydration,
in severe Diabetes (hyperosmolar coma)
• Intravenous infusion fluids should be isotonic
with plasma
Change in plasma osmolality cause cells to swell
or shrink

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CHANGE IN PLASMA OSMOLALITY
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ACTIVE TRANSPORT

• Transport of substances against chemical or electrical


gradient
• Involves expenditure of energy
• Uphill movement
• Also called as pumps
• Primary active & secondary active

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PRIMARY ACTIVE TRANSPORT

• Directly uses the energy obtained from the


hydrolysis of ATP
• Carrier mediated
• Features: Specificity, Saturation &Competitive
inhibition

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• Na K Pump (Na K ATpase) in all cells of body
• H ion secretion by Parietal cells of Stomach & tubular
cells of nephron (K H Pump)
• Calcium Pump in cell membrane which pumps Ca2
outside & the other pumps Ca2 into organelles-
mitochondria & cisternae of sarcoplasmic reticulum

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NA K PUMP

• The most common active transport system


• Seen in all cells
• Uses membrane bound ATPase as the carrier
• Spans the cell membrane
• Structure of carrier : alpha (larger) & beta (smaller)
subunits

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Alpha subunit has
a. 3 receptor sites for Na on the inner aspect
b. ATP binding site
c. Phosphorylation site
d. 2 receptor sites for K on the outer aspect & a
receptor site for Ouabin

Beta subunit has


a) anchor the protein complex in the lipid membrane

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Once 3 Na, 2K bind with carrier

ATPase function activated

ATP is split- liberates energy

Energy causes conformational change in


carrier

Extrudes 3 Na outside &2 k inside


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FUNCTIONS OF NA K PUMP

• Maintains the difference in ionic concentrations


between ICF &ECF (electrogenic)
• Maintains the RMP (inside–-ve to the outside) basic
requirement for transmitting nerve &muscle signal
• Maintains cell volume
• Helps in Secondary active transport
• Accounts for large part of BMR

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REGULATION OF NA K PUMP

Activity increased by
• Thyroid Hormone, Insulin aldosterone etc
Activity decreased by
• Low temperature, O2 lack, ouabin & other related
gycosides
• Digitalis-used in the treatment of heart failure

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CLINICAL IMPORTANCE

Sodium calcium counter transport


• Exists in cardiac muscle cell
• Exchanges intracellular ca2+ for extra cellular Na+
• This exchange depends on the concentration
gradient of Na+ across cell membrane
• If Na K pump is inhibited by digitalis intracellular
Na+ - Na + gradient  ca2+ extrusion --
intracellular ca2+
• Facilitates contraction of cardiac muscle

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SECONDARY ACTIVE TRANSPORT

• Coupled transport.
• Energy needed for “uphill” movement obtained from
“downhill” transport of Na+.
• Hydrolysis of ATP by Na+/K+ pump required indirectly to
maintain [Na+] gradient (store house of energy)

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SECONDARY ACTIVE TRANSPORT
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Co TRANSPORT

• Molecule or ion moving in the same direction as Na+.


• E.g. Transport of Glucose & amino acids- intestine &
kidney
• When Na &Glucose bind with Carrier protein
conformational change occurs
• Na & glucose transported inside the cell useful in oral re
hydration therapy

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COUNTER TRANSPORT (ANTIPORT)

• Molecule or ion moving in the opposite direction of Na+


• E.g. Sodium-calcium counter transport- in all cell
membrane
• Sodium Hydrogen counter transport –in PCT of kidney,
ClHCO3 in R.B.C

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SODIUM CALCIUM CO TRANSPORT
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EXOCYTOSIS & ENDOCYTOSIS

ENDOCYTOSIS :
• Substance is transported into the cell by the in folding of
the cell membrane around the substance and
internalising it.
• Types: Pinocytosis, Phagocytosis Receptor mediated
endocytosis

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ENDOCYTOSIS & EXOCYTOSIS
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ENDOCYTOSIS & EXOCYTOSIS
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• Phagocytosis(Cell Eating)
Is a process by which bacteria, dead tissue etc are
engulfed by leucocytes of the blood
• Pinocytosis(cell drinking)
Is same as phagocytosis except that the substances
ingested are in solution eg protein molecules
• Receptor mediated Endocytosis
Substance to be transported bind with a receptor which
is then engulfed by endocytosis eg transport of iron &
cholesterol into cells

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EXOCYTOSIS

• Process of discharge of substance from the cell


• Reverse of endocytosis
• Seen in cells that secrete protein compounds
• The membrane of the secretory vesicles fuse with the
cell membrane
• Area of fusion breaks
• Leaves the contents of the vesicles/granules outside the
cell &the cell membrane intact

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TRANSCYTOSIS

• Vesicular transport/Cytopempsis
• Small amounts of protein are transported out of
capillaries across endothelial cells by endocytosis on the
capillary side & by exocytosis on the interstitial side
• The transport uses vesicles coated with caveolin

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• Exocytosis adds to the total amount of membrane
surrounding the cell & Endocytosis helps to remove the
cell membrane
• Thus endocytosis- exocytosis coupling maintains the
surface area of the cell at its normal size

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Thank you!

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