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TRANSPORT ACROSS
CELL MEMBRANE
DR.JILSHA
OBJECTIVES
To get a better understanding of :
 Importance of cell membrane
 Passive transport
 Active transport
 Vesicular transport
 Other transport processes
INTRODUCTION TO CELL
MEMBRANE
 Cell membrane/plasma membrane is a thin, elastic, pliable
structure of 7.5-10 nm in diameter.
 It is composed almost entirely of proteins & lipids.
 It separates the contents of the cell from the external
environment and controls the exchange of substances
between the ECF & ICF.
STRUCTURE OF CELL MEMBRANE
 The basic structure of CM is a lipid bilayer – two layers of
phospholipids.
 1972, Singer and Nicolson proposed the fluid mosaic
model.
ARRANGEMENT OF LIPID BILAYER
 Two layers of phospholipids.
 Head end/polar end – phosphate moiety – hydrophilic –
directed outwards facing the aqueous phase (ECF&ICF).
 Tail end/non polar end – two chains of fatty acid –
hydrophobic – arranged towards the center of the CM.
 The lipid bilayer is a semi permeable
membrane
ARRANGEMENT OF PROTEINS
 Protein molecules float about in the lipid bilayer.
 Peripheral proteins & integral proteins (channel proteins,
carrier proteins, pumps, receptor proteins, enzyme
proteins).
ARRANGEMENT OF
CARBOHYDRATES
 The carbohydrates are attached either to the proteins -
Glycoproteins or to the lipids - Glycolipids.
 Throughout the surface , the carbohydrate molecules
form a thin loose covering called Glycocalyx.
TRANSPORT
 The physiological activities of a cell depend upon
substances like nutrients, oxygen and water, which must
be transported into the cell and at the same time,
metabolic waste must be transported out of the cell.
 The integral proteins that are required for transport are:
 Ion channels
 Water channels (Aquaporins)
ION CHANNELS
 Ion channels are pore-forming membrane proteins that
allow ions to pass through the channel pore.
 Most of them are gated-i.e., they open or close
spontaneously or in response to certain stimuli.
 Types of ion channels:
 Voltage gated
 Ligand gated
 Mechanical gated
ION CHANNELS
CLINICAL SIGNIFICANCE
CHANNELOPATHIES
 Channelopathies are a heterogeneous group of disorders
resulting from the dysfunction of ion channels. Mutations
in genes encoding the ion channels are the common cause.
 Examples include long QT syndrome, Brugada syndrome,
cystic fibrosis, thyrotoxic hypokalemic periodic paralysis
etc.,
WATER CHANNELS
Aquaporins also called as water channels are
channel proteins that form pores in the cell
membrane, mainly facilitating transport of
water between cells.
• Mutations in the aquaporin-2 gene cause
hereditary nephrogenic diabetes
insipidus in humans
CLINICAL
SIGNIFICANCE
TYPES OF TRANSPORT
TRANSPORT
ACTIVE
PRIMARY
SECONDARY
BULK VESICULAR
EXOCYTOSIS
ENDOCYTOSIS
Pinocytosis
Phagocytosis
Receptor mediated
endocytosis
TRANSCYTOSIS
PASSIVE
DIFFUSION
SIMPLE DIFFUSION
FACILITATED
DIFFUSIONOSMOSIS
PASSIVE TRASPORT
 It refers to the mechanism of transport of substances
along the gradient without expenditure of energy.
 Types: Diffusion & osmosis.
DIFFUSION
 It refers to passive transport of molecules from areas of
higher concentration to areas of lower concentration
 Types: Simple diffusion & facilitated diffusion.
DIFFUSION
FACTORS AFFECTING NET RATE OF DIFFUSION
 Fick’s law of diffusion
J=DA (C1-C2)
T
D-Diffusion coefficient
A-Surface area
C1&C2-Concentration on either sides
T-Thickness of the membrane
DIFFUSION
FACTORS THAT INFLUENCE DIFFUSION
RATES
EFFECT
Thickness of the membrane ↑ the thickness → ↓ the
rate of diffusion
Size of the molecule ↓ the size → ↑ the
diffusion
Temperature ↑ the Temp → ↑ the motion
of particles → ↑ the rate
of diffusion
Membrane surface area  Larger the area, faster is
the diffusion
FACTORS AFFECTING DIFFUSION
 CONCENTRATION GRADIENT : Simple diffusion α C1-C2
 ELECTRICAL POTENTIAL GRADIENT
SIMPLE DIFFUSION
 In simple diffusion, the kinetic movement of molecules or
ions occur through a membrane opening or through
intermolecular spaces without any interaction with carrier
proteins in the membrane.
 SD occurs by two pathways :
1.through the interstices of the lipid bilayer &
2.through watery channels
FACILITATED DIFFUSION
 It is also known as carrier mediated diffusion because a substance
transported in this manner diffuses through the membrane using a specific
carrier protein.
 A conformational change occurs in the carrier protein after the molecule to
be transported is bound at the receptor site. The repetitive spontaneous
configurational changes allow the diffusion of the molecule.
FACILITATED DIFFUSION
 In FD, the rate of diffusion ↑ with ↑ in concentration
gradient to reach a limit beyond which a further increase
in diffusion can’t occur. This is called saturation point.
 All the carrier proteins will be occupied and the system
operates at maximum capacity.
OSMOSIS
 Osmosis refers to diffusion of water/any solvent molecules through a
semi permeable membrane from a solution of lower concentration of
solutes to a solution of higher concentration of solutes.
OSMOTIC PRESSURE
 The minimum pressure which when applied on the side of higher
solute conc. that prevents osmosis is osmotic pressure.
OSMOLE
 It is the unit used in place of grams to express the conc.
In terms of osmotically active particles in a given soln.
 1 osmole = 1 g molecular wt of undissolved solute
 180 g of glucose = I g molecular wt of glucose = 1 osmole
 NaCl dissolves into Na and Cl
 58.5 g of NaCl = 2 osmoles
 1/1000 osmole = 1 milli Osmole
OSMOLALITY & OSMOLARITY
TONICITY
 Ability of a solution to affect fluid volume &
pressure within a cell.
 Isotonic : Osmolality similar to plasma. 0.9 %
NaCl
 Hypertonic : Osmolality ↑ than that of plama
 Hypotonic: Osmolality ↓ than that of plasma
TONICITY
CLINICAL SIGNIFICANCE
Total plasma osmolality ↑ in:
• Severe dehydration, severe Diabetes, ↑levels of urea in pts with
Renal Disease.
• Hyper osmolarity → water flow out of the brain → Hyperosmolar
coma.
↓ Plasma osmolality in:
• Administration of excessive 5% glucose- swelling of body tissues
ACTIVE TRANSPORT
 It refers to the mechanism of transport of
substances against the chemical/electrical
gradient using energy mainly in the form of ATP.
 Ionic substances : Na+ K+ Ca2+ Cl-
 Non ionic substances : glucose, amino acids, urea.
 Types : Primary and Secondary
TYPES OF CARRIER PROTEIN
SYSTEMS
PRIMARY ACTIVE TRANSPORT
 The energy is derived directly from the breakdown of
ATP or some other high energy phosphate compound.
 Some of the important pumps involved are
 Sodium potassium pump
 Calcium pump
 Potassium Hydrogen pump
SODIUM POTASSIUM PUMP
 Present in all the cells of the body.
 Active transport of Na ions outwards thro’ the CM and K
ions inwards simultaneously
STRUCTURE
 Carrier protein – α and β subunits. α subunit is mainly
concerned.
 Binding sites:
 3 intracellular – one each for binding Na+ (3Na+),
ATP, phosphorylation site
 2 extracellular – one each for binding K+ (2K+) and
MECHANISM
FUNCTIONS
 Controlling cell volume:
This is the most important function of the Na+ K+
pump without which most of the cells of the body will swell
up until they burst.
 Electrogenic activity:
Na+K+ pump act as electrogenic pump since it
produces a net movement of positive charge out of the cell
creating electrical potential across the CM. This is a basic
requirement in nerves & muscles to transmit the signals.
Na+-K+ PUMP
 Activity of Na+-K+ pump is :
↑ by diacyl glycerol, thyroid hormone,
aldosterone, insulin & G actin.
inhibited by low T, O2 lack, dopamine,
ouabain, glycosides (digitalis).
CALCIUM PUMP
 Two pumps :
 one in the CM which extrudes Ca2+ out of the cell and the other
actively transports cytoplasmic Ca into cell organelles
SECONDARY ACTIVE TRANSPORT
 In secondary active transport, the energy is derived
secondarily from the energy which has been stored in the
form of ionic conc. differences between the two sides of
the membrane.
 At many areas of the body, transport of some other
substance is coupled with the active transport of Na+
 Two types: Sodium co transport & Sodium counter
transport
SODIUM CO TRANSPORT
 Carrier protein act as symport. Glucose, amino acids, chloride and
iodine are transported by this method.
Sodium co transport of Glucose
SODIUM COUNTER TRANSPORT
 The carrier protein act as antiport. Eg., Sodium-Calcium counter
transport, Sodium-Hydrogen counter transport.
DIFF BETWEEN ACTIVE AND
PASSIVE TRANSPORT
VESICULAR TRANSPORT
 Involved in the transport of macromolecules such
as large protein molecules.
 Three mechanisms:
 Exocytosis
 Endocytosis
 Transcytosis
ENDOCYTOSIS
 It is the process in which the substance is transported into the cell
by infolding of the CM around the substance and internalizing it.
 Three types
 Pinocytosis(cell drinking)
 Phagocytosis(cell eating)
 Receptor mediated endocytosis
 Two pathways
 Constitutive
 Clathrin mediated
TYPES
CONSTITUTIVE PATHWAY
Molecule
Contact
with CM
CM
invaginates
Endocytic
vesicle
formation
Fusion of
non
cytoplasmic
sides of the
CM
Invagination
pinched off
CONSTITUTIVE PATHWAY
CLATHRIN MEDIATED
STRUCTURE
 Clathrin is a protein that plays a major role in the
formation of coated vesicles.
 Clathrin was first isolated and named by Barbara Pearse
in 1976
 It is triskelion shaped and composed of three clathrin
heavy chains and three light chains.
MECHANISM
Endocytosis
progresses
Clathrin
surrounds
endocytic vesicle
Clathrin falls off
and recycles
CAVEOLAR ENDOCYTOSIS
 Clathrin independent endocytosis involving flask shaped invaginations called
caveolae.
 Caveolae have been implicated in cell signalling, Lipid regulation.
EXOCYTOSIS
 Reverse of endocytosis
 Two pathways
 Constitutive-proteins from golgi initially enter secretory granules.
Prohormones to mature hormones before exocytosis
 Non constitutive-No processing or storage
MECHANISM
Substance to
be extruded
Vesicle/granule Fusion with CM
Contents
released to the
exterior
MECHANISM
TRANSCYTOSIS
 Vesicular transport within the cell. common in epithelial cells
 Macromolecules are captured in vesicles on one side of the cell, drawn across
the cell and ejected on the other side
OTHER TRANSPORT PROCESSES
 Transport across epithelia – naturally assemble in the form of sheets
of tightly linked cells resting on basal membrane. They form tight
junctions.
 Transport through cell proper
 Ultrafiltration : occurs at the barrier between the blood and the
filtrate in the glomerular capsule of kidneys.
 The high hydrostatic pressure forces small molecules like water,
glucose, amino acids, urea through the filter, from the blood in the
glomerular capsule across the basement membrane of the Bowman’s
capsule and into the renal tubule.
SUMMARY
 The cell membrane plays an active role in transport of
substances,
 Lipid soluble substances pass directly through the cell
membrane.
 Water and other small ions pass through channel proteins.
 Large molecules pass through carrier proteins by active
transport.
 ATP is the major source of energy in active transport.
 Bulk transport of substances occur by vesicular transport.
Transport across cell membrane

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Transport across cell membrane

  • 2. OBJECTIVES To get a better understanding of :  Importance of cell membrane  Passive transport  Active transport  Vesicular transport  Other transport processes
  • 3. INTRODUCTION TO CELL MEMBRANE  Cell membrane/plasma membrane is a thin, elastic, pliable structure of 7.5-10 nm in diameter.  It is composed almost entirely of proteins & lipids.  It separates the contents of the cell from the external environment and controls the exchange of substances between the ECF & ICF.
  • 4. STRUCTURE OF CELL MEMBRANE  The basic structure of CM is a lipid bilayer – two layers of phospholipids.  1972, Singer and Nicolson proposed the fluid mosaic model.
  • 5. ARRANGEMENT OF LIPID BILAYER  Two layers of phospholipids.  Head end/polar end – phosphate moiety – hydrophilic – directed outwards facing the aqueous phase (ECF&ICF).  Tail end/non polar end – two chains of fatty acid – hydrophobic – arranged towards the center of the CM.  The lipid bilayer is a semi permeable membrane
  • 6. ARRANGEMENT OF PROTEINS  Protein molecules float about in the lipid bilayer.  Peripheral proteins & integral proteins (channel proteins, carrier proteins, pumps, receptor proteins, enzyme proteins).
  • 7. ARRANGEMENT OF CARBOHYDRATES  The carbohydrates are attached either to the proteins - Glycoproteins or to the lipids - Glycolipids.  Throughout the surface , the carbohydrate molecules form a thin loose covering called Glycocalyx.
  • 8. TRANSPORT  The physiological activities of a cell depend upon substances like nutrients, oxygen and water, which must be transported into the cell and at the same time, metabolic waste must be transported out of the cell.  The integral proteins that are required for transport are:  Ion channels  Water channels (Aquaporins)
  • 9. ION CHANNELS  Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore.  Most of them are gated-i.e., they open or close spontaneously or in response to certain stimuli.  Types of ion channels:  Voltage gated  Ligand gated  Mechanical gated
  • 11. CLINICAL SIGNIFICANCE CHANNELOPATHIES  Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels. Mutations in genes encoding the ion channels are the common cause.  Examples include long QT syndrome, Brugada syndrome, cystic fibrosis, thyrotoxic hypokalemic periodic paralysis etc.,
  • 12. WATER CHANNELS Aquaporins also called as water channels are channel proteins that form pores in the cell membrane, mainly facilitating transport of water between cells. • Mutations in the aquaporin-2 gene cause hereditary nephrogenic diabetes insipidus in humans CLINICAL SIGNIFICANCE
  • 13. TYPES OF TRANSPORT TRANSPORT ACTIVE PRIMARY SECONDARY BULK VESICULAR EXOCYTOSIS ENDOCYTOSIS Pinocytosis Phagocytosis Receptor mediated endocytosis TRANSCYTOSIS PASSIVE DIFFUSION SIMPLE DIFFUSION FACILITATED DIFFUSIONOSMOSIS
  • 14. PASSIVE TRASPORT  It refers to the mechanism of transport of substances along the gradient without expenditure of energy.  Types: Diffusion & osmosis. DIFFUSION  It refers to passive transport of molecules from areas of higher concentration to areas of lower concentration  Types: Simple diffusion & facilitated diffusion.
  • 15. DIFFUSION FACTORS AFFECTING NET RATE OF DIFFUSION  Fick’s law of diffusion J=DA (C1-C2) T D-Diffusion coefficient A-Surface area C1&C2-Concentration on either sides T-Thickness of the membrane
  • 16. DIFFUSION FACTORS THAT INFLUENCE DIFFUSION RATES EFFECT Thickness of the membrane ↑ the thickness → ↓ the rate of diffusion Size of the molecule ↓ the size → ↑ the diffusion Temperature ↑ the Temp → ↑ the motion of particles → ↑ the rate of diffusion Membrane surface area  Larger the area, faster is the diffusion
  • 17. FACTORS AFFECTING DIFFUSION  CONCENTRATION GRADIENT : Simple diffusion α C1-C2  ELECTRICAL POTENTIAL GRADIENT
  • 18. SIMPLE DIFFUSION  In simple diffusion, the kinetic movement of molecules or ions occur through a membrane opening or through intermolecular spaces without any interaction with carrier proteins in the membrane.  SD occurs by two pathways : 1.through the interstices of the lipid bilayer & 2.through watery channels
  • 19. FACILITATED DIFFUSION  It is also known as carrier mediated diffusion because a substance transported in this manner diffuses through the membrane using a specific carrier protein.  A conformational change occurs in the carrier protein after the molecule to be transported is bound at the receptor site. The repetitive spontaneous configurational changes allow the diffusion of the molecule.
  • 20. FACILITATED DIFFUSION  In FD, the rate of diffusion ↑ with ↑ in concentration gradient to reach a limit beyond which a further increase in diffusion can’t occur. This is called saturation point.  All the carrier proteins will be occupied and the system operates at maximum capacity.
  • 21. OSMOSIS  Osmosis refers to diffusion of water/any solvent molecules through a semi permeable membrane from a solution of lower concentration of solutes to a solution of higher concentration of solutes.
  • 22. OSMOTIC PRESSURE  The minimum pressure which when applied on the side of higher solute conc. that prevents osmosis is osmotic pressure.
  • 23. OSMOLE  It is the unit used in place of grams to express the conc. In terms of osmotically active particles in a given soln.  1 osmole = 1 g molecular wt of undissolved solute  180 g of glucose = I g molecular wt of glucose = 1 osmole  NaCl dissolves into Na and Cl  58.5 g of NaCl = 2 osmoles  1/1000 osmole = 1 milli Osmole
  • 25. TONICITY  Ability of a solution to affect fluid volume & pressure within a cell.  Isotonic : Osmolality similar to plasma. 0.9 % NaCl  Hypertonic : Osmolality ↑ than that of plama  Hypotonic: Osmolality ↓ than that of plasma
  • 27. CLINICAL SIGNIFICANCE Total plasma osmolality ↑ in: • Severe dehydration, severe Diabetes, ↑levels of urea in pts with Renal Disease. • Hyper osmolarity → water flow out of the brain → Hyperosmolar coma. ↓ Plasma osmolality in: • Administration of excessive 5% glucose- swelling of body tissues
  • 28. ACTIVE TRANSPORT  It refers to the mechanism of transport of substances against the chemical/electrical gradient using energy mainly in the form of ATP.  Ionic substances : Na+ K+ Ca2+ Cl-  Non ionic substances : glucose, amino acids, urea.  Types : Primary and Secondary
  • 29. TYPES OF CARRIER PROTEIN SYSTEMS
  • 30. PRIMARY ACTIVE TRANSPORT  The energy is derived directly from the breakdown of ATP or some other high energy phosphate compound.  Some of the important pumps involved are  Sodium potassium pump  Calcium pump  Potassium Hydrogen pump
  • 31. SODIUM POTASSIUM PUMP  Present in all the cells of the body.  Active transport of Na ions outwards thro’ the CM and K ions inwards simultaneously STRUCTURE  Carrier protein – α and β subunits. α subunit is mainly concerned.  Binding sites:  3 intracellular – one each for binding Na+ (3Na+), ATP, phosphorylation site  2 extracellular – one each for binding K+ (2K+) and
  • 33. FUNCTIONS  Controlling cell volume: This is the most important function of the Na+ K+ pump without which most of the cells of the body will swell up until they burst.  Electrogenic activity: Na+K+ pump act as electrogenic pump since it produces a net movement of positive charge out of the cell creating electrical potential across the CM. This is a basic requirement in nerves & muscles to transmit the signals.
  • 34. Na+-K+ PUMP  Activity of Na+-K+ pump is : ↑ by diacyl glycerol, thyroid hormone, aldosterone, insulin & G actin. inhibited by low T, O2 lack, dopamine, ouabain, glycosides (digitalis).
  • 35. CALCIUM PUMP  Two pumps :  one in the CM which extrudes Ca2+ out of the cell and the other actively transports cytoplasmic Ca into cell organelles
  • 36. SECONDARY ACTIVE TRANSPORT  In secondary active transport, the energy is derived secondarily from the energy which has been stored in the form of ionic conc. differences between the two sides of the membrane.  At many areas of the body, transport of some other substance is coupled with the active transport of Na+  Two types: Sodium co transport & Sodium counter transport
  • 37. SODIUM CO TRANSPORT  Carrier protein act as symport. Glucose, amino acids, chloride and iodine are transported by this method. Sodium co transport of Glucose
  • 38. SODIUM COUNTER TRANSPORT  The carrier protein act as antiport. Eg., Sodium-Calcium counter transport, Sodium-Hydrogen counter transport.
  • 39. DIFF BETWEEN ACTIVE AND PASSIVE TRANSPORT
  • 40. VESICULAR TRANSPORT  Involved in the transport of macromolecules such as large protein molecules.  Three mechanisms:  Exocytosis  Endocytosis  Transcytosis
  • 41. ENDOCYTOSIS  It is the process in which the substance is transported into the cell by infolding of the CM around the substance and internalizing it.  Three types  Pinocytosis(cell drinking)  Phagocytosis(cell eating)  Receptor mediated endocytosis  Two pathways  Constitutive  Clathrin mediated
  • 42. TYPES
  • 43. CONSTITUTIVE PATHWAY Molecule Contact with CM CM invaginates Endocytic vesicle formation Fusion of non cytoplasmic sides of the CM Invagination pinched off
  • 45. CLATHRIN MEDIATED STRUCTURE  Clathrin is a protein that plays a major role in the formation of coated vesicles.  Clathrin was first isolated and named by Barbara Pearse in 1976  It is triskelion shaped and composed of three clathrin heavy chains and three light chains.
  • 47. CAVEOLAR ENDOCYTOSIS  Clathrin independent endocytosis involving flask shaped invaginations called caveolae.  Caveolae have been implicated in cell signalling, Lipid regulation.
  • 48. EXOCYTOSIS  Reverse of endocytosis  Two pathways  Constitutive-proteins from golgi initially enter secretory granules. Prohormones to mature hormones before exocytosis  Non constitutive-No processing or storage MECHANISM Substance to be extruded Vesicle/granule Fusion with CM Contents released to the exterior
  • 50. TRANSCYTOSIS  Vesicular transport within the cell. common in epithelial cells  Macromolecules are captured in vesicles on one side of the cell, drawn across the cell and ejected on the other side
  • 51. OTHER TRANSPORT PROCESSES  Transport across epithelia – naturally assemble in the form of sheets of tightly linked cells resting on basal membrane. They form tight junctions.  Transport through cell proper  Ultrafiltration : occurs at the barrier between the blood and the filtrate in the glomerular capsule of kidneys.  The high hydrostatic pressure forces small molecules like water, glucose, amino acids, urea through the filter, from the blood in the glomerular capsule across the basement membrane of the Bowman’s capsule and into the renal tubule.
  • 52. SUMMARY  The cell membrane plays an active role in transport of substances,  Lipid soluble substances pass directly through the cell membrane.  Water and other small ions pass through channel proteins.  Large molecules pass through carrier proteins by active transport.  ATP is the major source of energy in active transport.  Bulk transport of substances occur by vesicular transport.