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MEMBRANE TRANSPORTERS
PRADEEP SINGH,HINA YASEEN
M.Sc. MEDICAL BIOCHEMISTRY
HIMSR, JAMIA HAMDARD
CONTENT
 Introduction
 Fluid mosaic model
 Transport proteins
 Gated channel proteins
 Aquaporins
 Transport mechanism
 Passive transport
 Active transport
 Endocytosis
INTRODUCTION
 Plasma membrane, defines the boundary of the cell and separates its
internal content from the environment.
 Membrane separates the fluid into two compartment extra cellular(ECF)
fluid and intracellular fluid(ICF).
 It is a selective barrier to the passage of the molecules between ECF and
ICF.
 Plasma membrane consists of both lipid and Protein.
 Thickness of the cell membrane varies from 75-110Å.
FLUID MOSAIC MODEL OF PLASMA MEMBRANE
 In 1972, Jonathan Singer and Garth Nicolson proposed Fluid Mosaic Model.
 Membrane are viewed as quasi fluid model in which Proteins are inserted into lipid
bilayers.
 Major lipids of the membrane-
1. Phospholipid
a) Phosphatidylcholine
b) Phosphatidylethanolamine
c) Phosphatidylserine
d) Sphingomyelin
e) Phosphatidylinositol
2. Glycolipids
3. Cholesterol
4. CARBOHYDRATE
5. PROTEINS
•Integral Proteins
Example :- Spectrin and Ankyrin present on the RBC’s.
•Peripheral Proteins
Example:- Glucoporin
TRANSPORT OF SOLUTE AND
SOLVENT ACROSS THE LIPID BILYER
TRANSPORT PROTEINS
TWO TYPES OF TRANSPORT PROTEINS ARE PRESENT-
1. CARRIER PROTEINS
a) Uniport (non-coupled)
b) Symport (coupled)
c) Antiport (coupled)
2. CHANNEL PROTEINS
A. Gated channel
B. Non-gated channel
CARRIER PROTEINS
 Undergoes conformational changes
 Binds to molecules on one side &
then undergoes conformational
change to transfer molecules on
other side.
e.g.- Facilitated diffusion of sugar,
amino acid and nucleosides.
TYPES OF GATED CHANNEL PROTEINS
 Voltage gated channels
 Ion gated channel
 Ligand gated channel
 Mechanically gated channel
CHANNEL PROTEIN
 Protein channels are selectively permeable.
 The channels are named after the ions which diffuse through it.
Such as:-Na+ channels ,K+ channels, etc.
Regulation of channels
1. Opened channel are called Non-gated channels
2. Closed channel are called gated channels
VOLTAGE GATED CHANNEL
 They generate action potential.
 They have a crucial role in excitable cells such as neuronal and muscle tissues.
 Allow a rapid and co-ordinated depolarization in response to triggering voltage
change.
VOLTAGE GATED Na+ CHANNEL
 Discovered by Hodgkin and Huxley in 1952 .
 Small amount of Na+ enters the cell down its
electrochemical gradient.
 If Na+ channel remain open it could result in
spasm.
Example:- Includes those selectively permeable to Na+ , K+ , Ca2+ .
CLINICAL CORRELATIONS
 Mutation in genes that encoded voltage gated channel in skeletal muscle cells
causes MYOTONIA, a condition that are delay in muscle relaxation after voluntary
contraction, causing painful spasm.
 Other mutation effects like epilepsy, ataxia, Lambert-eaton myasthenic syndrome,
Alzheimer’s, Parkinson’s disease etc.
LIGAND GATED CHANNEL
 These channels open on binding of the hormonal substance.
Eg:- release of acetylcholine at neuromuscular junction
GABA
 Acetylcholine is released that causes the entry of Na+ ions from ECF into NMJ.
MECHANICALLY GATED CHANNEL
 Opened by some mechanical stress.
 Eg:- pressure receptors, stretch receptor
AQUAPORINS(AQP)
 Specialized water channel in their
plasma membrane facilitate the water
flow.
 Aquaporins assemble as a
homotetramers, in which each
monomer, consists of six membrane-
spanning α- helical domains.
 Other uncharged molecules are also
transported through this channel like
glycerol
 e,.g.-Water permeability of epithelial
lining of kidney due to AQP-2.
 ADH regulates this AQP-2 which
TRANSPORT MECHANISM
Passive transport
 Transport of substances along the concentration gradient or electrical gradient or
both(electrochemical gradient).
 It does not require energy.
Types of passive transport:-
1. Simple diffusion
2. Facilitated diffusion or carrier mediated diffusion
SIMPLE DIFFUSION
 Molecules simply dissolves in the phospholipid bilayer and diffuses across it.
 Relative diffusion rate of any substance is directly proportional to its concentration
gradient.
 Diffusion is always from higher concentration to lower concentration.
Example:- gases (oxygen and carbon dioxide)
molecules (benzene)
small polar but uncharged molecule(water and ethanol)
FACILITATED DIFFUSION
 Movement of solute along the concentration gradient.
 It is may be carrier protein and channel protein mediated.
 Allow charged and polar molecule.
Example:- carbohydrate, amino acid, nucleoside and ion etc.
MECHANISM OF FACILITATED DIFFUSION
 A PING-PONG model is put fourth to explain facilitated diffusion.
 According to this mechanism, a transport protein exists in two conformations.
 In the pong conformation, it is exposed to the side with high solute concentration. The
protein undergoes conformational change (ping state) change to expose to the side with
low solute concentration.
 Hormones regulate through the facilitated diffusion,
E.g.:- insulin increase glucose transport in muscle and adipose tissue.
GLUCOSE TRANSPORTERS
CHLORIDE BICARBONATE EXCHANGER
OF THE ERYTHROCYTE
ACTIVE TRANSPORT
 Against the concentration gradient.
 Requires energy.
 Mediated by carrier protein.
 Metabolic energy is used to transport the
ions and molecules such as absorbtion of
sunlight, oxidation reaction.
Ways of active
transport
1. Coupled transporters
2. ATP-Driven pumps
Types
 Active transport is of two types:-
1. Primary active transport
2. Secondary active transport
PRIMARY ACTIVE TRANSPORT
 Solute accumulation is coupled directly to an exergonic chemical reaction, such as
conversion of ATP to ADP+Pi.
Example:- 1. Na+- K+ ATPase ( carrier protein to transport of Na+ and K+)
Discovered by Jens and Skou in 1957.
2. Ca2+ ATPase in endoplasmic/sarcoplasmic. reticulum
SODIUM POTASSIUM PUMP
Sodium Potassium pump inhibitors
 Digitalis and Ouabain.
 Inhibit the dephosphorylation of pump.
 Treatment of congestive heart disease.
TRANSPORT ATPase
 Transport ATPase are the ATP power pump
 Four major type of ATPase associated with membrane-
1. P- ATPase
2. V-ATPase
3. F-ATPase
4. ABC transporter
P-ATPase
It maintains the difference in ionic composition of the ECF and ICF.
1. Na+ - K+ ATPase of plasma membrane.
2. H+ ATPase of plasma membrane of fungi.
3. Ca2+ - ATPase of sarcoplasmic reticulum.
V-ATPase
 Maintains the pH.
 Proton transporting ATPase from the cytosolic to the
exoplasmic face of the membrane against the
electrochemical gradient.
 Found on the vacuolar membranes in plant cell,
endosomal and lysosmal membranes in animals, and
plasma membrane of osteoclast.
F-ATPase
 Structurally related to V-ATPase pumps is distinct family of F-ATPase.
 In eukaryotes, F-ATPase found on the inner membrane of mitochondria.
 In bacteria, it is present in the plasma membrane.
ABC TRANSPORTER (ATP BINDING CASSETTE)
 Large family of ATP dependent transporter that pump wide
range of molecules.
 It has two Transmembrane domains (TMD), two Nucleotide
binding domains (NBD).
 Movement of domains, expose the solute binding sites one
side of the membrane and then after conformational
change tranferred to the other side.
Cont.
 ABC transporter family is p-glycoprotein ( multidrug resistance protein 1).
 MDR1has ability to confer in lung cancer cell.
 Makes the cell resistant to cytotoxic drugs used for chemotherapy
 Mutation results in cystic fibrosis.
 Cystic fibrosis transmembrane conductance regulator (CFTR) also belong to ABC
transporters.
SECONDRY ACTIVE TRANSPORT
 Transport occurs when endergonic (uphill) transport
of one solute is coupled with the exergonic (downhill)
flow of a different solute.
 It is either symport or antiport.
 Na+- glucose transport is the example of symport.
ENDOCYTOSIS
 Term given by Christian de Duve in 1963.
 Eukaryotic cells are also able to take up macromolecules and
particle from the surrounding by a distinct process called
endocytosis.
 Types of Endocytosis:-
 Phagocytosis
 Pinocytosis
 Receptor mediated endocytosis
Contd.
SUMMARY
Transport
Protien
Carrier
Mediated
Channel
Mediated
Gated
Voltage Ion Ligand Mechanically
Non Gated
TRANSPORT
MECHANISM
PASSIVE
TRANSPORT
SIMPLE
FACILITATED
ACTIVE
TRANSPORT
PRIMARY
SECONDARY
Transport across Plasma Membrane

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Transport across Plasma Membrane

  • 1. MEMBRANE TRANSPORTERS PRADEEP SINGH,HINA YASEEN M.Sc. MEDICAL BIOCHEMISTRY HIMSR, JAMIA HAMDARD
  • 2. CONTENT  Introduction  Fluid mosaic model  Transport proteins  Gated channel proteins  Aquaporins  Transport mechanism  Passive transport  Active transport  Endocytosis
  • 3. INTRODUCTION  Plasma membrane, defines the boundary of the cell and separates its internal content from the environment.  Membrane separates the fluid into two compartment extra cellular(ECF) fluid and intracellular fluid(ICF).  It is a selective barrier to the passage of the molecules between ECF and ICF.  Plasma membrane consists of both lipid and Protein.  Thickness of the cell membrane varies from 75-110Å.
  • 4. FLUID MOSAIC MODEL OF PLASMA MEMBRANE  In 1972, Jonathan Singer and Garth Nicolson proposed Fluid Mosaic Model.  Membrane are viewed as quasi fluid model in which Proteins are inserted into lipid bilayers.  Major lipids of the membrane- 1. Phospholipid a) Phosphatidylcholine b) Phosphatidylethanolamine c) Phosphatidylserine d) Sphingomyelin e) Phosphatidylinositol 2. Glycolipids 3. Cholesterol
  • 5. 4. CARBOHYDRATE 5. PROTEINS •Integral Proteins Example :- Spectrin and Ankyrin present on the RBC’s. •Peripheral Proteins Example:- Glucoporin
  • 6. TRANSPORT OF SOLUTE AND SOLVENT ACROSS THE LIPID BILYER
  • 7. TRANSPORT PROTEINS TWO TYPES OF TRANSPORT PROTEINS ARE PRESENT- 1. CARRIER PROTEINS a) Uniport (non-coupled) b) Symport (coupled) c) Antiport (coupled) 2. CHANNEL PROTEINS A. Gated channel B. Non-gated channel
  • 8. CARRIER PROTEINS  Undergoes conformational changes  Binds to molecules on one side & then undergoes conformational change to transfer molecules on other side. e.g.- Facilitated diffusion of sugar, amino acid and nucleosides.
  • 9. TYPES OF GATED CHANNEL PROTEINS  Voltage gated channels  Ion gated channel  Ligand gated channel  Mechanically gated channel
  • 10. CHANNEL PROTEIN  Protein channels are selectively permeable.  The channels are named after the ions which diffuse through it. Such as:-Na+ channels ,K+ channels, etc. Regulation of channels 1. Opened channel are called Non-gated channels 2. Closed channel are called gated channels
  • 11. VOLTAGE GATED CHANNEL  They generate action potential.  They have a crucial role in excitable cells such as neuronal and muscle tissues.  Allow a rapid and co-ordinated depolarization in response to triggering voltage change.
  • 12. VOLTAGE GATED Na+ CHANNEL  Discovered by Hodgkin and Huxley in 1952 .  Small amount of Na+ enters the cell down its electrochemical gradient.  If Na+ channel remain open it could result in spasm.
  • 13. Example:- Includes those selectively permeable to Na+ , K+ , Ca2+ .
  • 14. CLINICAL CORRELATIONS  Mutation in genes that encoded voltage gated channel in skeletal muscle cells causes MYOTONIA, a condition that are delay in muscle relaxation after voluntary contraction, causing painful spasm.  Other mutation effects like epilepsy, ataxia, Lambert-eaton myasthenic syndrome, Alzheimer’s, Parkinson’s disease etc.
  • 15. LIGAND GATED CHANNEL  These channels open on binding of the hormonal substance. Eg:- release of acetylcholine at neuromuscular junction GABA  Acetylcholine is released that causes the entry of Na+ ions from ECF into NMJ.
  • 16.
  • 17. MECHANICALLY GATED CHANNEL  Opened by some mechanical stress.  Eg:- pressure receptors, stretch receptor
  • 18. AQUAPORINS(AQP)  Specialized water channel in their plasma membrane facilitate the water flow.  Aquaporins assemble as a homotetramers, in which each monomer, consists of six membrane- spanning α- helical domains.  Other uncharged molecules are also transported through this channel like glycerol  e,.g.-Water permeability of epithelial lining of kidney due to AQP-2.  ADH regulates this AQP-2 which
  • 19. TRANSPORT MECHANISM Passive transport  Transport of substances along the concentration gradient or electrical gradient or both(electrochemical gradient).  It does not require energy. Types of passive transport:- 1. Simple diffusion 2. Facilitated diffusion or carrier mediated diffusion
  • 20. SIMPLE DIFFUSION  Molecules simply dissolves in the phospholipid bilayer and diffuses across it.  Relative diffusion rate of any substance is directly proportional to its concentration gradient.  Diffusion is always from higher concentration to lower concentration. Example:- gases (oxygen and carbon dioxide) molecules (benzene) small polar but uncharged molecule(water and ethanol)
  • 21. FACILITATED DIFFUSION  Movement of solute along the concentration gradient.  It is may be carrier protein and channel protein mediated.  Allow charged and polar molecule. Example:- carbohydrate, amino acid, nucleoside and ion etc.
  • 22. MECHANISM OF FACILITATED DIFFUSION  A PING-PONG model is put fourth to explain facilitated diffusion.  According to this mechanism, a transport protein exists in two conformations.  In the pong conformation, it is exposed to the side with high solute concentration. The protein undergoes conformational change (ping state) change to expose to the side with low solute concentration.
  • 23.  Hormones regulate through the facilitated diffusion, E.g.:- insulin increase glucose transport in muscle and adipose tissue.
  • 26. ACTIVE TRANSPORT  Against the concentration gradient.  Requires energy.  Mediated by carrier protein.  Metabolic energy is used to transport the ions and molecules such as absorbtion of sunlight, oxidation reaction. Ways of active transport 1. Coupled transporters 2. ATP-Driven pumps
  • 27. Types  Active transport is of two types:- 1. Primary active transport 2. Secondary active transport
  • 28. PRIMARY ACTIVE TRANSPORT  Solute accumulation is coupled directly to an exergonic chemical reaction, such as conversion of ATP to ADP+Pi. Example:- 1. Na+- K+ ATPase ( carrier protein to transport of Na+ and K+) Discovered by Jens and Skou in 1957. 2. Ca2+ ATPase in endoplasmic/sarcoplasmic. reticulum
  • 30. Sodium Potassium pump inhibitors  Digitalis and Ouabain.  Inhibit the dephosphorylation of pump.  Treatment of congestive heart disease.
  • 31. TRANSPORT ATPase  Transport ATPase are the ATP power pump  Four major type of ATPase associated with membrane- 1. P- ATPase 2. V-ATPase 3. F-ATPase 4. ABC transporter
  • 32. P-ATPase It maintains the difference in ionic composition of the ECF and ICF. 1. Na+ - K+ ATPase of plasma membrane. 2. H+ ATPase of plasma membrane of fungi. 3. Ca2+ - ATPase of sarcoplasmic reticulum.
  • 33. V-ATPase  Maintains the pH.  Proton transporting ATPase from the cytosolic to the exoplasmic face of the membrane against the electrochemical gradient.  Found on the vacuolar membranes in plant cell, endosomal and lysosmal membranes in animals, and plasma membrane of osteoclast.
  • 34. F-ATPase  Structurally related to V-ATPase pumps is distinct family of F-ATPase.  In eukaryotes, F-ATPase found on the inner membrane of mitochondria.  In bacteria, it is present in the plasma membrane.
  • 35. ABC TRANSPORTER (ATP BINDING CASSETTE)  Large family of ATP dependent transporter that pump wide range of molecules.  It has two Transmembrane domains (TMD), two Nucleotide binding domains (NBD).  Movement of domains, expose the solute binding sites one side of the membrane and then after conformational change tranferred to the other side.
  • 36. Cont.  ABC transporter family is p-glycoprotein ( multidrug resistance protein 1).  MDR1has ability to confer in lung cancer cell.  Makes the cell resistant to cytotoxic drugs used for chemotherapy  Mutation results in cystic fibrosis.  Cystic fibrosis transmembrane conductance regulator (CFTR) also belong to ABC transporters.
  • 37. SECONDRY ACTIVE TRANSPORT  Transport occurs when endergonic (uphill) transport of one solute is coupled with the exergonic (downhill) flow of a different solute.  It is either symport or antiport.  Na+- glucose transport is the example of symport.
  • 38. ENDOCYTOSIS  Term given by Christian de Duve in 1963.  Eukaryotic cells are also able to take up macromolecules and particle from the surrounding by a distinct process called endocytosis.  Types of Endocytosis:-  Phagocytosis  Pinocytosis  Receptor mediated endocytosis