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Membrane Transport
STRUCTURE OF CELL MEMBRANE
• barrier to water and water-soluble substances
ions glucoseurea
Lipid Bilayer:
CO2
O2N2
halothane
H2O
Ion ConcentrationsThe maintenance of solutes on both sides of
the membrane is critical to the cell and homeostasisHelps to keep the cell from rupturing
Concentration of ions on either side varies widelyNa+ and Cl- are higher outside the cellK+ is higher inside the cellMust balance the number of positive and
negative charges, both inside and outside cell
Composition of ECF is maintained by different systems like nervous , endocrine, CVS, GIT, renal , respiratory in a coordinated fashion
Composition of ICF is maintained by cell membrane which mediates the transport of materials b/w ICF and ECF through different transport mechanisms.
Membrane Transport Proteins
Many molecules must move back and forth from inside and outside of the cell
Most cannot pass through without the assistance of proteins in the membrane bilayerPrivate passageways for select substances
Each cell has specific set of proteins
Movement of Molecules
Permeability of a membraneAnything that passes between a cell and the surrounding ECF must be able to pass through the plasma membrane.
If a substance can pass thru the membrane, the membrane is said to be permeable to that substance; if a substance cannot pass, the membrane is impermeable to it. The plasma membrane is selectively permeable in that it permits some substances to pass through while excluding others.
Impermeable Membranes
Ions and hydrophilic molecules cannot easily pass thru the hydrophobic membrane.
Small and hydrophobic molecules can
2 Major Classes of proteinsCarrier proteins – move the solute across the
membrane by binding it on one side and transporting it to the other sideRequires a conformation change
Channel proteins – small hydrophilic pores that allow for solutes to pass through (watery spaces)Use diffusion to move acrossAlso called ion channels when only ions movingCalled aquaporins if water is moving thru them
Types of Proteins
Carrier vs Channel
Channels, if open, will let solutes pass if they have the right size and chargeTrapdoor-like
Carriers require that the solute fit in the binding site
carriers are specific like an enzyme and its substrate
Both the channel proteins and carrier proteins are usually highly selective in the types of molecules or ions that are allowed to cross the membrane.
These proteins are also present in membranes of cell organelles
In cell organelles
Membrane Ion Channels
Passive, or leak, channels – always open
Gated which open and close
Chemically (or ligand)-gated channels – open with binding of a specific neurotransmitter (the ligand)
Voltage-gated channels – open and close in response to changes in the membrane potential
Mechanically-gated channels – open and close in response to physical deformation of receptors
Types of plasma membrane ion channels
3 Types of Channels
Simple Diffusion
KEY WORDSSolvent: (relatively large amount of a substance
which is the dissolving medium; in the body is water).Solute: (relatively small amount of a substance which
is the dissolved substance and it dissolves in the solvent).
Solution: is a homogenous mixture of a solute in a solvent.
Concentration: of a solvent is the amount of solute dissolved in a specific amount of solution.
Concentration gradient: difference in the concentration of a solute on two sides of a permeable membrane.
Equilibrium: exact balance between 2 opposing forces.
Dynamic: continuous motion or movement.
Types of Cellular Transport 1 Passive Transport
cell doesn’t use energy1. Diffusion (simple & facilitated)2. Osmosis
2 Active Transportcell does use energy
1. Primary active transport
2. Secondary active transporthigh
low
This is gonna
be hard
work!!
high
low
Weeee!!!
•Animations of Active Transport & Passive Transport
continue 3. Endocytosis:
Pinocytosis Phagocytosis
4. Exocytosis
Two major modes of membrane transport
I. Simple (Passive)DiffusionI. Simple (Passive)Diffusionno carriers is involvedno carriers is involved
There are two major modes of mediated diffusion: passive transport (or facilitated
diffusion) and active transport
II. Mediated DiffusionII. Mediated Diffusion
is carried out by proteins, is carried out by proteins, peptides, and small peptides, and small molecular weight carriersmolecular weight carriers
((ions, uncharged organic compounds, peptides, and even proteins can be transported)
•Molecules that are transported through the cell membrane via simple diffusion include organic molecules, such as benzene and small uncharged molecules, such as H2O, O2, N2, urea, glycerol,and CO2
DiffusionMolecules are in continuous random motion
(Brownian motion)Evident mostly in liquids and gases whose
molecules are free to moveGreater the concentration of molecules
greater the likelihood of collision and movement to chamber with low concentration
1)The net movement of particles
2)from a region of higher concentration
3)to a region of lower concentration,
4)down the concentration gradient
. The energy that causes diffusion is the energy of the normal kinetic motion of molecules
Diffusion
High concentration Low concentration
Diffusion can occurs either through the lipid
membrane or through the carrier proteins or
through channel proteins
outside of cell
inside of cell
TYPES OF DIFFUSION:
1. Simple diffusion2. Facilitated diffusion
1: SIMPLE DIFFUSIONSimple diffusion means the net movement of molecules from higher concentration to lower conc. through “PROTEIN CHANNELS” or “INTERCELLULAR SPACE” of cell membrane without carrier proteins and energy
Diffusional equilibriumNet movement
ceases when concentration of particles is equal everywhere within the solution although random movement of the particles continues
Diffusion of two solutes
Simple diffusion occur through the cell membrane
by two pathways
1) lipid soluble substance through the interstices of lipid bilayer
2) through channel proteins if water soluble and ion and small
A: SIMPLE DIFFUSION THROUGH LIPID BILAYER
CO2
O2
N2
Fatty acidsAlcoholThey all are lipid soluble (uncharged and
also non polar) and can diffuse through the membrane
TRANSPORT OF H2O
H2O passes through lipid bilayer because its size is small and also thru aquaporins
SIMPLE DIFFUSION THROUGH PROTEIN CHANNEL
Larger water soluble substances and charged particles (electrolytes) passes through protein channels , not through lipid bilayer.
Ion Channels
Ion channels are very specific with regards to pore size and the charge on the molecule to be movedMove mainly Na, K, Cl and Ca
Reason of impermeabilityof charge particles
They are hydrated ions so bigger size.
Outer pole of lipid bilayer have negative charge………
Characteristics of protein channelsSelective permeability
Opening and closing of gates
Selective permeability of protein channelsIt may be due to :
Diameter of the channelIts shapeNature of electric charges
Gating of channelsGating provides in controlling the ion
permeability of the channels
The opening and closing of gates are controlled in two ways:
1) VOLTAGE GATING 2) LIGAND GATING3) MECHANICAL GATING
Voltage Gated channels in Simple Diffusion:Sodium Channels: •0.3 by 0.5 nm in diameter•Negatively charged on the inside•Because of the negative charges they pull the positively charged sodium ion inside, away from the water molecule. Potassium channel:•0.3 by 0.3 nm in diameter•No negative charge on the inside•Pull the hydrated K ion inside. As no negative charge on the inside of the channel, no attractive forces for the Na ion… also, Na ions hydrated form is far too big….
Ligand gated ion channel
Mechanically gated channels
Diffusion of low lipid soluble substance and too large for channels
Like glucose pass thru the carrier proteins
e.g. facilitated diffusion and active transport
Factors affecting rate of simple diffusion 1 Permeability of membrane 2 Concentration difference 3. Pressure difference 4 Electrical difference 5. Surface area of the membrane 6. molecular weight of the substance
7. Thickness of the membrane
Factors that affect the net rate of diffusion:
1. Concentration difference (Co-Ci)
net diffusion D (Co-Ci)
Figure 4-8; Guyton & Hall
The steeper the concentration gradient, the faster diffusion takes place
Fast rate of diffusion
Steeper concentration gradient
Concentration Gradient
Less steep concentration gradient
Slow rate of diffusion
Permeability of the membrane to substance to be transported
3. Pressure difference
• Higher pressure results in increased energy available to cause net movement from high to low pressure.
Figure 4-8; Guyton & Hall
Surface area of the membrane
Molecular weight of substance
Thickness of membrane
Electrical gradient
Electrochemical Gradient
This gradient determines the direction of the solute during passive transport
Fick’s Law of Diffusion:
2: FACILITATED DIFFUSION Definition: is the transport mechanism
which require “CARRIER PROTEIN”
Mechanism:1. Molecule + CARRIER PROTEIN (loosely
bound)2. Conformational change in carrier protein3. Molecule detached from carrier4. No energy or ATP required
FACILITATED DIFFUSION Glucose Amino acids Other simple carbohydrates such as : Galactose Mannose Arabinose Xylose. All require “carrier protein” for their
transport, so called “carrier mediated diffusion”
Means by which glucose is transported into cells muscles liver and RBCs
Insulin increases number of carriers for glucose in plasma membrane of different cells
Characteristics of facilitated diffusionSPECIFICITYSATURATION COMPETITION
Specificity: e.g. glucose cannot bind to amino acid carriers and vice versa.
SATURATION
Facilitated diffusion always have Vmax Simple diffusion Facilitated diffusion
Saturation: A limited no. of carrier binding sites are available within a particular plasma membrane for a specific substance. Thus, there is a limit to the amount of substance a carrier can transport across the membrane in a given time. This is called Transport Maximum (Tm).
Mediated-Transport Systems
In simple diffusion,flux rate is limited only by the concentration gradient.
In carrier-mediated transport, the number of available carriers places an upper limit on the flux rate.
Competition: Several different substances are competing for the same carrier site.
THINK!
How does water get through the HYDROPHOBIC Plasma membrane?
How does water get through the HYDROPHOBIC Plasma membrane?
Answer: Even though water is polar and so highly insoluble in the membrane lipids, it readily passes through the cell membrane thru 2 ways:1.Water molecules are small enough to move through the spaces created between the phospholipid molecules’ tails2.In many cells, membrane proteins form aquaporins, which are channels specific for the passage of water. About a billion water molecules can pass in single file through an aquaporin channel in one second. (renal tubules)
OsmosisDefinition:
The diffusion of water molecules
through a partially permeable membrane
from a solution of high water concentration
to a solution of lower water concentration
Down the concentration gradient
: sucrose:water molecules
Partially permeable membrane
Chapter 3 The Plasma Membrane and Membrane PotentialHuman Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Fig. 3-9, p. 63
OSMOSISDiffusion of water through the semi
permeable membrane from a solution of higher water concentration towards a solution of lower water concentration
Partially-permeable membrane
More free water molecules on this side of membrane
Water-solute particle is too large to pass through membrane
Free water molecules diffuse in this direction
Osmosis: due to difference in net hydrostatic pressure
The hydrostatic pressure of pure water is higher than that of solution on right
As this column rises higher, it will exert increasing pressure. At some point that hydrostatic pressure will reach an equilibrium, at which pointno more net water will move across thesemi-permeable membrane.
This pressure is the ‘osmotic pressure’of the starting solution on the right.
Osmotic pressureThe amount of pressure required to stop
further the process of osmosis is called osmotic pressure Driving force is the osmotic pressure caused by the difference in water pressure
Osmotic pressure
The greater the solute conc. of a solution, the greater its osmotic
pressure. OR
The greater the no. of ion/molecule when dissolved greater the osmotic pressure.
ExampleSeparate pure water
from a sugar solution with semi permeable membrane
Both have same hydrostatic pressure
Osmosis take water from side 1 to side 2 because solution on side 1 has more hydrostatic pressure
Will all water go to side 2?No it stops after some time. This is the
equilibrium state
As water moves by osmosis to side 2.
Solution on side 2 has two tendencies now
Tendency to push water back to side 1 due to greater hydrostatic pressure
Tendency to pull water by osmosis back to side 2
Equilibrium is achieved when tendency to pull water to side 1 and to push water into side 2 balances out
Equilibrium state
• Osmotic pressure depends on the number of solutes/unit volume (rather than chemical nature of solutes or mass of the particles)
REASONEach particle in a solution regardless of its
mass exerts on average the same amount of pressure against the membrane
K.E. = mv2 2
If more mass then less velocity and vice versa so KE on average is same for both small and large particle
isosmotic(osmotic pressure is equal)
Solutes are dissolved particles in solution (any type)
hypersmotic(higher osmotic pressure)
hyposmotic(lower osmotic pressure)
osmoleTo express the concentration of a solution in
terms of no. of particles the unit osmole is used in place of grams
1 osmole is 1 gram molecular weight of osmotically active solute.
molarity - moles of solute / liters of solvent (moles/liter = Molar)
mole - grams of substance = mol. wt. substance
l mole H = 1 gram H1 mole C = 12 grams C1 mole NaCl = 58 grams NaCl1 mole C6H12O6 = 180 grams C6H12O6
58 grams NaCl/l liter water = 1 mole NaCl/liter = 1 Molar NaCl (lM NaCl)
180 g Glucose/1 liter water = 1 mole glucose/liter = 1 Molar glucose (1M Glucose)
Osmolarity/OsmolalityTo describe the total number of
osmotically active particles per litre of solution term osmolarity is used
IT IS OSMOLES PER LITER OF SOLUTION
The higher the osmolarity, the greater the osmotic pressure of the solution.
Two solutions can have the same molarity but may have different osmolarities. E.g.
OsM of 1 M glucose solution =1 OsM OsM of 1 M NaCl solution = 2 OsM
The solution that has I osmole of solute dissolved in each Kg of water have an osmolality of 1 osmole per liter.
The solution that has 1/1000 osmoles dissolved per Kg has an osmolality of I milliosmole
The normal osmolarity of ECF and ICF is 300mOsm per Kg of water
Relation between osmolarity and molarity
mOsm (millisomolar) = index of the concn or mOsm/L of particles per liter soln
mM (millimolar) = index of concn of or mM/L molecules per liter soln
150 mM NaCl = 300 mOsm
300 mM glucose = 300 mOsm
Relation of osmolality to osmotic pressureAt normal body temp. concentration of 1 osmole
per liter will cause osmotic pressure of 19300 mm Hg osmotic pressure in the solution
1 milli osmole will be equivalent to 19.3mm Hg osmotic pressure
Total osmotic pressure = 300 x 19.3 = 5790mmHgWe take 5500 0smotic pressure because many
ions in the body fluids are highly attracted to one another and therefore can’t exert their full osmotic pressure
Tonicity is a relative termIsotonic SolutionIsotonic Solution - both solutions have
same concentrations of solute
Hypotonic SolutionHypotonic Solution - One solution has a lower concentration of solute than another.
Hypertonic SolutionHypertonic Solution - one solution has a higher concentration of solute than another.
Hypotonic – The solution on one side of a membrane where the solute concentration is less than on the other side. Hypotonic Solutions contain a low concentration of solute relative to another solution.
Hypertonic – The solution on one side of a membrane where the solute concentration is greater than on the other side. Hypertonic Solutions contain a high concentration of solute relative to another solution.
RED CELL IN ISOTONIC SOLUTIONCytoplasm and
solution outside the cell has same concentration of solutes so no net movement of water so cell maintain its shape
Red blood cell in Low water potential
1. Cytoplasm has higher water potential compared to the solution outside the cell.
2. Water leaves by osmosis
3. Cell shrinks and little spikes appear on cell surface membrane. (Crenation)
Red blood cell in High water potential
1. Cytoplasm has lower water potential compared to solution outside cell
2. Water enters by osmosis
3. Animal cell will swell and may bursts as it does not have a cell wall to protect it.
Special categories of transport 1. BULK TRANSPORT:
It is the transport mechanism in which large quantity of substances transported from high pressure to low pressure e.g. exchange thru capillary membrane
Membrane TransportVesicular transport
Material is moved into or out of the cell wrapped in membrane
Active method of membrane transportTwo types of vesicular transport
Endocytosis Process by which substances move into cell Pinocytosis – nonselective uptake of ECF Phagocytosis – selective uptake of multimolecular
particle Exocytosis
Provides mechanism for secreting large polar molecules
Transport in VesiclesRequires energy (ATP)Involves small membrane sacEndocytosis: importing materials into cell
Phagocytosis: ingestion of particles such as bacteria into white blood cells (WBCs)
Pinocytosis: ingestion of fluidExocytosis: exporting materials
111
112
ENDOCYTOSISLarge molecule or macromolecules
transported by endocytosis.
Endocytosis are of 3 types a. Pinocytosis b. Phagocytosis c. Receptor mediated endocytosis
PINOCYTOSIS (Cell drinking) 1. non selective uptake of particle( in the
form of droplet fluid ECF) bind with outer surface of membrane.
2 Cell membrane evaginate around the droplets
3 It is detached from cell membrane forms ENDOSOME.
PINOCYTOSIS (Cell drinking) Cont..4. Primary lysosomse attach with
edosome ,converted into secondry lysosomes.
5. Hydrolytic enzymes present in secondary lysosome becomes activated and digest the content of endosome
PINOCYTOSIS (Cell drinking)
PHYGOCYTOSIS (Cell eating)
RECEPTOR MEDIATED ENDOCYTOSIS
Chapter 3 The Plasma Membrane and Membrane PotentialHuman Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Table 3-2c, p. 74
ACTIVE TRANSPORTDefinition:
Active transport is a carrier-mediated transport wherein molecules and ions are moved against their concentration gradient across a membrane and requires expenditure of
energy.
Active transport is divided into 2 types according to the source of the energy used.
Types of Active Transport
In both instances, transport depends on carrier proteins. , the carrier protein functions differently from the carrier in facilitated diffusion because it is capable of imparting energy to the transported substance to move it against the electrochemical gradient by acting as an enzyme and breaking down the ATP itself.
Primary Active Transport
• The primary active transport carriers are termed as pumps.
•molecules are “pumped” against a concentration gradient at the expense of energy (ATP) – direct use of energy
Secondary Active Transport
• transport is driven by the energy stored in the concentration gradient of another molecule (Na+) – indirect use of energy
Types of Active Transport:
In primary active transport, the energy is derived directly from breakdown of adenosine triphosphate (ATP) or from some other high-energy phosphate compound.In secondary active transport, the energy is derived secondarily from energy stored in the form of an ion concentration gradient between the two sides of a cell membrane, created originally by primary active transport. Thus, energy is used but it is “secondhand” energy and NOT directly derived from ATP.
Primary Active TransportIn primary active transport, energy in the form of ATP
is required to change the affinity of the carrier protein binding site when it is exposed on opposite sides of plasma membrane.
The carrier protein also acts as an enzyme that has ATPase activity, which means it splits the terminal phosphate from an ATP molecule to yield ADP and inorganic phosphate plus free energy.
Examples:1.Sodium-Potassium Pump (every cell).2. Hydrogen pump: occurs at 2 places in the human
body: - in the gastric glands of the stomach
- In the kidneys3. Ca pump (muscles)
Na-K PUMP:
• It has the following structure:
1. 3 receptor sites for binding Na ions on the portion of the protein that protrudes to the inside of the cell.
2. 2 receptor sites for potassium ions on the outside.
3. The inside portion of this protein near the sodium binding site has ATPase activity.
Na+-K+ Pump is a Cycle
Na+-K+ PumpMoves K+ while moving Na+
Works constantly to maintain [Na+] inside the cell – Na+ comes in thru other channels or carriers
FUNCTIONS OF SODIUM-POTASSIUM PUMP:
1. Control the Volume of each cell: It helps regulate cell volume by controlling the concentrations of solutes inside the cell and thus minimizing osmotic effect that would induce swelling or shrinking of the cell. If the pump stops, the increased Na concentrations within the cell will promote the osmotic inflow of water, damaging the cells.
2. Electrogenic nature of the pump: It establishes Na and K concentration gradients across the plasma membrane of all cells; these gradients are critically important in the ability of nerve and muscle cells to generate electrical signals essential to their functioning.
3. Energy used for Secondary active transport: The steep Na gradient is used to provide energy for secondary active transport.
2. Ca2+ ATPase
• present on the cell membrane and the sarcoplasmic reticulum• maintains a low cytosolic Ca2+ concentration
• found in parietal cells of gastric glands (HCl secretion) and intercalated cells of renal tubules (controls blood pH)
Examples of Primary Active Transport Pumps:
1) Na+/K+ -ATPase pump- found in the plasma membrane- 3 Na+ are pumped out of cytosol and 2 K+ are pumped into the
cytosol
2) Ca+2 -ATPase pump- found in the plasma membrane, & endoplasmic reticulum
membranes- pumps Ca+2 out of cytosol and either into the ER or the extracellular
fluid
3) H+ -ATPase- found in the plasma membrane, lysosomes, & mitochondria inner
membrane- pumps H+ out of the cell and into extracellular fluid- pumps H+ into lysosomes to be used as digestive enzymes- used in the electron transport chain of mitochondria
4) H+/K+ -ATPase - used in acid secreting cells of the kidneys and stomach- pumps one H+ out of cell and one K+ into the cell
Saturation• similar to facilitated diffusion• rate limited by Vmax of the transporters
Energetics• up to 90% of cell energy expended for active transport!
Competition
Specificity
Secondary Active Transport
1. Co-transport (co-porters): substance is
transported in the same direction as the “driver” ion (Na+)
Examples:
inside
outside
Na+ AA Na+ gluc 2 HCO3-Na+
- co-transport and counter-transport -
2. Counter-transport (anti-porters): substance is
transported in the opposite direction as the “driver” ion (Na+)
Examples:
Na+
Ca2+
Na+
H+ Cl-/H+
Na+/HCO3-
outside
inside
SECONDARY ACTIVE TRANSPORTCO-TRANSPORTSymportNa moves downhillMolecule to be co-
transported moved in the same direction as Na, i.e. to the inside of the cell.
E.g. Na with glucose and amino acids.
Site: intestinal lumen and renal tubules of kidney.
COUNTER TRANSPORTAnti-port Na moves downhillMolecule to be counter-
transported moves in the opposite direction to Na, i.e. to the outside of the cell.
E.g. Na with Calcium and Hydrogen ions.
Site: Na-Ca counter transport in almost all cells of the body and Na-H+ in the proximal tubules of the kidney.
Types of Secondary Transporters
Symporters (two solutes (two solutes move in same direction) move in same direction) Lac- permease, NaLac- permease, Na++/glucose /glucose transporter)transporter)
AntiportersAntiporters (two solutes (two solutes move in opposite directionsmove in opposite directions
NaNa++/Ca/Ca2+2+ exchanger) exchanger)
UniportersUniporters (mitochondrial Ca(mitochondrial Ca2+2+ uniporter and NHuniporter and NH++
44--transporter in plants transporter in plants require Hrequire H++ gradient) gradient)
Transcellular Transport of Glucose / AA
Na+
glucose
AA
Na+
low high
epitheliumlumenextracellular
fluid
Na+
Na+
K+
K+
AAAA
glucoseglucose
low
Diffusion Active Transport• occurs down a concn. gradient• no mediator or involves a “channel” or “carrier”• no additional energy
• occurs against a concn. gradient• involves a “carrier”
• requires ENERGY
Figure 4-2; Guyton & Hall
Summary through a video
