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									Membrane Structure and
      Function



    Transport of Substances through
          the cell membrane
Chapter 2 (cell membrane parts) and 4 of Guyton and Hall, 11th ed.



                                                                1
                    Lecture outline
I. Membrane Function and                 iii. Facilitated
    Structure                                      a. characteristics
    A. Phospholipids                     iv. Rates of simple vs. facilitated
    B. Proteins                      B. Active
    C. Carbohydrates                     i. Primary
    D. Cholesterol                       ii. Secondary
II. Transport across the
    membrane
    A. Passive
         i. Osmosis and osmotic
    pressure
         ii. Simple
           a. Factors that influence
           b. Examples
                                                                          2
• In the cell membrane are phospholipids,
  proteins, sugars, etc., that separate intra
  and extra cellular fluid, and limit what can
  travel through it. Proteins create channels
  or pores. They can be perceived as
  antigens. There are some proteins that are
  only on the inside of the cell membrane,
  which turn on activities in the cell.

                                             3
• Phospholipids are antipathic (water loving and water
  hating). One side can attach to other water loving
  molecules on the phosphate portion. The two fatty acid
  (FA) tails are made of long chains of hydrocarbons. The
  FAs dislike water, but can bind with hydrophobic
  molecules. If we only had one layer of phospholipids, the
  membrane would orient toward the water loving fluid. But
  FAs don’t like the water, so with a bi-layer, the FA can be
  happy, and the phosphate can be happy. Substances
  that love lipids can get to the middle of the membrane,
  but water loving has a hard time crossing.

                                                            4
               Membrane Function
• Organizes chemical activities
  of cell
   – separates cells from outside
     environment
   – controls passage of molecules
     across membranes
   – partitions organelle function in
     eukaryotes
   – provides reaction surfaces and
     organizes enzymes and their
     substrates
   – Proteins embedded provide
     function, too!
       •   Channels
       •   Carriers
       •   Receptors
       •   Cell adhesion
       •   Enzymes
       •   Identification markers, etc.

                                          5
           Membrane Structure
– phospholipids have polar “head”
  (hydrophilic) and nonpolar “tail”
  (hydrophobic)
– form stable bilayer in water with
  heads out and tails in
– hydrophobic interior from fatty
  acid tails forms barrier to
  hydrophilic molecules
– Chemistry: glycerol + two fatty
  acids and phosphate head




                                      6
• Proteins can be integral (throughout the
  membrane) or peripheral (one side or the other).
• Integral protein can create a pore, or channel
  with a gate that can open and close. Proteins on
  the surface of the membrane can bind a
  chemical. A peripheral protein on the inside of
  the membrane can instigate a series of
  enzymatic reactions within the cell. Some
  proteins can bind substances on the outside of
  the membrane and transport them into cell
  (facilitative diffusion)                         7
Proteins:
•Provide function to a membrane
•Can move laterally
•membrane also shows “sidedness”
        •interior - attachment to cytoskeleton
        •exterior - carbohydrates, extracellular matrix (next slide)
• defined by mode of association with the lipid bilayer
 – integral: channels, pores, carriers, enzymes, etc.
 – peripheral: enzymes, intracellular signal mediators, etc.




            K+                                                     8
• Sugars outside of the cell can attach to the phosphate
  heads or to the proteins (that will now be a glycoprotein).
  If there are many glucose molecules on the outside of
  the cell, it will make the outside of the membrane
  negatively charged. Every cell is set up like a battery,
  with a separation of charges across the cell membrane.
  This is called potential; one area is more negative than
  another area. There is storage of electricity, like a
  battery. The inside of the cell should be more negative
  than the outside of the cell. But if there is a glycocalyx
  (sugar bundle) on the outside of the cell, they make it a
  negative charge.
                                                            9
Carbohydrates
•glycoproteins (majority of integral proteins)
• proteoglycans
•glycolipids (approx. 10%)
• involved in cell-cell attachments/interactions
• play a role in immune reactions


                      (-)                          (-)   (-)
                             (-)                               (-)
GLYCOCALYX                                (-)
                                   (-)




                                                                     10
• Cholesterol maintains the fluidity of cell membrane so
  the lipids are not frozen in place, but not so much that
  there are gaps in the cell membrane. There needs to be
  a balance of flexibility and stability. Cholesterol is a lipid,
  so it’s located in the middle of the membrane. If you try
  to apply a lipid to a phospholipid membrane without
  proteins in it, and you will see that hydrophobic
  molecules get through it easier than hydrophilic. Gases
  like CO2, O2, and small molecules like ethanol could get
  through. If you try to add water loving molecules
  (charged molecules like glucose and positive ions), they
  can pass. Water can also get through. Water loving
  substances get across the lipid center by active and
  passive transport.                                            11
Cholesterol:
• present in membranes in varying amounts
• increases membrane FLEXIBILITY and STABILITY
during different temperatures
• helps to increase hydrophobicity of membrane

                (-)                     (-)   (-)
                      (-)                           (-)
                                  (-)
                            (-)




                                                          12
Transport across a membrane:
Understand this!
              LIPIDS by themselves are a:
   • barrier to water and water-soluble substances
   •Allow lipid soluble substances to cross through membrane

                  glucose                       CO2    O2
                     ions                                N2
                                                H2O

hydrophilic
  “head”
hydrophobic
  FA “tail”




                                                               13
 Movement across the cell Membrane
… but, in a living cell, hydrophilic molecules still get across! How?

                                          CO2
                  ions H2O                  N2 O2
                    glucose




                                                                 14
Passive Transport                              Active Transport
• occurs down a concn. gradient • occurs against a concn. gradient
• no mediator (simple)          • involves a “pump”
•or involves a “channel” or     • requires cellular ENERGY (ATP)
“carrier”(facilitated)
• no additional energy beyond
kinetic energy




           Osmosis &


                               Passive transport              15
           Figure 4-2; Guyton & Hall
• Passive transport means no cellular
  energy required, no ATP used.
• Active transport means ATP is used,
  either directly or indirectly.
• Passive transport makes substances
  move from high to low concentration,
  down their gradient.
• Active transport is when at least one
  solute is moved against its
  concentration gradient.                 16
• Osmosis is passive, no ATP is used. Water
  moves from high to low concentration. That is,
  water moves from low particles to high particles.
  If you have two sides of a membrane, and the
  particles can’t move, water will move. How does
  it get through? There are aqua pores created
  just for water passage. You have to have a gene
  to make these pores. The wrong amount of
  pores causes water imbalances.

                                                  17
                                  Osmosis:
     - net flow of water across a semipermeable
    membrane (permeable to water but not solute)
  Osmosis occurs from pure water toward a water/salt solution.
  Water moves down its concentration gradient.




This movement is
affected by the
solute
concentration
(osmotic force)
and hydrostatic
forces (more on
this later in the
course                                                           18
              Figure 4-9; Guyton & Hall
• When you did the PhysioEx osmosis activity,
  you applied pressure, did not see volume
  change, just measured the hydrostatic pressure.
• The idea of molarity and osmolarity is expressed
  in this example:
• Solution A is 100 g of something added to water
• Solution B is 1000g added to water.
• The g% is different.


                                                 19
• To calculate molarity, you have to divide grams by
  molecular weight. Both of the above solutions have
  same molarity, one mole per liter. That means they both
  have the same number of molecules. They are different
  sizes, but still the same number. If neither side
  dissociates, same number of particles, but if A
  dissociates into 3 particles, how many osmoles is it?
  Three. If A is separated from B by a membrane that only
  allows water to move, where will water go? It moves
  from B to A, and the volume in A will climb, unless you
  apply pressure (3osm) to stop it from rising. Molarity is
  the number of molecules.
                                                          20
Major determinant of osmotic pressure- differences in
total solute or particle concentration NOT MASS!
                               A                     B

                            100 g                 1000 g
                            in 1 L                in 1L


                          Solute A              Solute B
                          Mw = 100              Mw = 1000
Which has the greatest molar concentration?
Which has the greatest number of molecules?(6.02 x 1023 Molecules)
Which solution has the greatest osmolality? (assume no dissociation)
If “A” has a dissociation factor of 3, now which solution has the greatest osmolality?
         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                   21
• Simple diffusion of a solute is also
  passive. Rate of diffusion depends on
• How big is the gradient? How steep is the
  slide? The greater the difference, the
  faster the rate of diffusion, if the solute is
  permeable across the gradient.
• Is the solute permeable?


                                                   22
• Simple diffusion of small molecules can diffuse without
  any protein assistance. Water loving larger molecule
  needs a protein. Some pores are open all the time, and
  those that can use it, will diffuse when they want. If
  always open, is a pore. If not always open, it is a
  channel. Channels are gated. The gate can be open
  or closed. They open when a special chemical (ligand)
  binds to it, called ligand operated channels (LOC), like a
  key. Some open by electrical change, like garage door
  opener, called VOC voltage operated channel. If it
  doesn’t have permeability, gate closed, can only get
  through slowly. If it is open, solute can diffuse. There is
  no ATP used, not active transport.                          23
 Non-carrier mediated transport
1. Simple Passive Diffusion
• is tendency of molecules to
  spread out spontaneously from
  area of high concentration to
  area of low concentration
• At equilibrium, there is not net
  gain nor loss of cell fluid.
• It is passive; molecule diffuses
  down concentration gradient
  without input of cellular energy
• Need permeability
• Need concentration gradient
  (chemical/ electrical)             Can a molecule move from side
                                     B to side A?
                                       Figure 4-8; Guyton & Hall   24
                   Simple Diffusion
(a) lipid-soluble molecules move readily across the membrane
       (rate depends on lipid solubility)
(b) water-soluble molecules cross via channels or pores (these are
proteins!).
       •ungated
       •Gated channels- Chemical and Electrical gated channels
 (c) Different molecules diffuse independently of each other
                      (a)              (b)




                                                                     25
      Voltage gated channel
• These cause a change in the electrical
  potential (separation of charges). They are
  specific, for instance, one may only allow
  sodium to cross. You would need a
  different one to allow potassium to pass.
  The amino acids dictate what things can
  go through them. Need many different
  types of proteins, many pores.
• Ligand gated channel
• A chemical binds to open the gate.         26
Ion Channels- allow simple diffusion
 Characteristics:
  ungated
     • determined by size, shape, distribution of charge, etc.
  gated
     • voltage (e.g. voltage-dependent Na+ channels)
     • ligand activated (e.g. nicotinic ACh receptor channels)

                                                            in



                                                            out
                                          Na+ and   other
               Na+                        ions                   27
    How was this
    discovered?
•   “Patch Clamp”
•   Nobel Prize in Physiology & Medicine -1991
•   Neher and Sakmann



       in




       out
                                  Na+
• Facilitated diffusion is still passive, no ATP is used. It is the
  same end result as simple diffusion. The difference is that it
  requires a protein to physically bind to it and move it across
  the cell membrane. Therefore, it can be saturated. The rate at
  which solute is moved is limited by the number of carriers you have.
  When drunken people in a bar want to go home when the bar
  closes, and there is only one taxi, it would take a long time for all the
  people to get home. To get home faster, need more carriers. If
  each carrier moves one carrier, rest of molecules has to wait their
  turn. If there are too many glucose molecules in the nephron, you
  will reabsorb some of them them in the bloodstream, and some will
  spill out in the urine. This is because glucose transporters are
  saturated in the nephron.


                                                                         29
Facilitated Diffusion (also called carrier mediated diffusion)
•   Specific proteins facilitate
    diffusion across membranes
    –   no cellular energy required
    –   Carrier protein interacts with
        solute
    –   Specificity – carrier only acts
        upon specific substrates.
    –   Saturation – the rate of transport
        will reach a maximum based on
        the number of carriers available
        in the membrane. (This is animated
        on next slides)
    Rate of diffusion is limited by
        •   Vmax of the carrier protein
        •    the density of carrier
            proteins in the membrane
            (i.e., number per unit area)

                                             Figure 4-7; Guyton & Hall   30
    =solute
       = transporter
                                   1
                   1/min
Ex. Pass-through                   2
rate is 1 each
minute             2/min
                                   3
                   3/min
                                   4
                   4/min
                                   5
                   5/min
Transport maximum is reached when carriers
are saturated, Vmax.                         31
Rate of Simple vs. Facilitated Diffusion

• If you increase concentration gradient,
  rate increases as well.
• Facilitative will reach velocity
  maximum. When it is saturated, it levels
  off.




                                         32
Simple vs. Facilitated
                                 simple diffusion
                                 rate of diffusion  (Co-Ci)
    rate of
    diffusion

           Vmax
            Tm                 facilitated diffusion




                  Concn of substance

         What limits maximum rate of
                                                               33
         facilitated diffusion?
      Primary active transport
• This uses ATP directly. A protein whose name ends in
  ATPase is one that hydrolyses ATP, creating a
  concentration gradient. Going skiing, do you climb the
  mountain? No, you take the lift, using the energy in the
  chair lift. Ski down a slope with a rope around your waist,
  that rope will pull up the next person. That provides the
  stored energy to pull the second person up. This is
  secondary active transport. The protein does not use
  the ATP. As one goes down, liberates energy that
  helps a different molecule to move against its
  concentration gradient.

                                                           34
                 Active Transport


Primary Active Transport             Secondary Active
   – molecules are “pumped”            Transport
     against a concentration           – transport is driven by the
   – gradient at the expense             energy stored in the
     of energy (ATP)                     concentration gradient of
                                         another molecule (Na+)
   – direct use of cellular energy
                                       – One molecule down
                                         gradient
                                       – One molecule against
                                         gradient
                                       – indirect use of energy
                                                                      35
• Most ATPs are used for primary active transport.
  The most common is sodium-potassium
  ATPase. It moves two solutes against their
  gradients. It keeps sodium outside and
  potassium inside. When a channel is made, the
  substance that comes first tells you the
  protein has a preference for that substance.
  Sodium-potassium ATPase moves 3 sodium
  ions for every two potassium ions. They still
  need carrier proteins. This job can only be done
  at a certain rate.
                                                 36
          Primary Active Transport
• Cells expend energy for
  active transport
    – transport protein involved in
      moving solute against
      concentration gradient
    – energy from ATP
    – rate limited by Vmax of the
      transporters
•    up to 90% of cell energy
                                       Na+/K+ ATPase
    expended for active                plays an important role in regulating osmotic
    transport!                         balance by maintaining Na+ and K+ balance
                                        requires one to two thirds of cell’s energy!
    – active transport of two          Others exist- calcium ATPase and H+ ATPase
      solutes in opposite directions
      often coupled
                                                                              37
   Secondary active transport
• ATP is not directly used by the protein. Three sodium
  ions are kicked out, 2 potassium ions are pulled in.
• Another integral protein creates a protein, binds to
  sodium, allowing it to move down the concentration
  gradient. If it had high levels of glucose, it would pull in
  glucose against its concentration gradient, and into the
  cell. This Na-glucose system is a co-transporter. A co-
  transporter takes two substances in the same
  direction across the cell membrane. An anti-porter
  takes two substances in opposite directions.


                                                            38
Secondary Active Transport
          - co-transport and counter-transport -

   1. Co-transport (co-porters): substance is
       transported in the same direction as the “driver”
       ion (Na+)
    Examples:
                           outside
    Na+   AA        Na+ gluc            Na+ 2 HCO3-




                               inside                      39
2. Counter-transport (anti-porters): substance is
   transported in the opposite direction as the “driver” ion
   (Na+)


    Examples:
                                 outside
     Na+             Na+        Na+/HCO3-




           Ca2+            H+              Cl-/H+
                                                               40
                                  inside
•   Sample test questions: given the following list, answer the questions below.
•   Osmosis
•   Simple Diffusion
•   Facilitative Transport
•   Primary active Transport
•   Secondary active Transport

•   Which has net movement of water? Simple diffusion
•   Select all that apply: This type of transport moves solutes down the
    concentration gradient. Simple, facilitative, secondary,

•   Which ones have a solute moved against its gradient: primary and
    secondary
•   Which is moved against its gradient and ATP is directly used: primary




                                                                               41

								
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