Plasma Membrane Transport

Question 1

Plasma Membrane

Answer 1

The cell surface plasma membrane is a PHOSPHOLIPID BILAYER

• Shown here as 5 nm thick (5-10 nm), the membrane is just two layers wide
• Shown in upper left corner is a TEM of the plasma membrane of a red blood cell

Question 2

Hydrophilic

Answer 2

means that a molecule loves water

A hydrophilic molecule is also necessarily lipophobic.

Question 3

Hydrophobic

Answer 3

means that a molecule fears water

A hydrophobic molecule is also necessarily lipophilic.

Question 4

Lipophilic

Answer 4

means that a molecule loves lipids

A hydrophobic molecule is also necessarily lipophilic.

Question 5

Lipophobic

Answer 5

means that a molecule fears lipids

A hydrophilic molecule is also necessarily lipophobic.

Question 6

Hydrophilic interactions

Answer 6

Cells are largely water so their interactions with aqueous solutions is important!

Hydrophilic or polar molecules such as acetone form favorable electrostatic interactions (hydrogen bonds) with water molecules, which are also polar. Thus, polar molecules readily dissolve in water (i.e., they are water-soluble).

Question 7

Hydrophobic Interactions

Answer 7

Cells are largely water so their interactions with aqueous solutions is important!

Hydrophobic or non-polar molecules, such as 2-methyl propane, cannot form hydrogen bonds with water molecules. Such molecules are therefore not soluble (i.e., they are insoluble) in water.

Question 8

Bilayer - Phospholipids

Answer 8

Diagram of the structure of the phospholipids that compose cell membranes.

• Amphipathic (= amphiphilic)
• Hydrophilic vs. Hydrophobic regions

Question 9

Bilayer - Cholesterol

Answer 9

• Cholesterol is a sterol molecule
• Cholesterol orients itself with its polar hydroxyl group close to the polar head groups of phospholipids.
• Cholesterol is said to not reduce the fluidity of the lipid bilayer, but it is thought to render the bilayer less permeable to small, water-soluble molecules (cholesterol is hydrophobic).

Question 10

Lipid Rafts

Answer 10

Lipid rafts are microdomains or subdomains within the phospholipid bilayer (usually the plasma membrane) that act as hot spots for signal transduction.

Cholesterol, sphingolipids, glycolipids, glycoproteins, GPI-anchored proteins and other integral transmembrane proteins are enriched within these domains.

Question 11

Bilayer - Proteins

Answer 11

A wide variety of mechanisms transduce signals across the plasma membrane. Proteins can create or carry a signal inside the cell to intracellular signaling proteins.

Question 12

Membrane Transport

Answer 12

Cells need to import molecules from the extracellular environment. Cells also need to export molecules to the extracellular environment. This can be challenging due to the plasma membrane.

Question 13

Selective Permeability

Answer 13

Some molecules can get across the plasma membrane of cells, whereas other molecules cannot.

• Lipid-soluble molecules can freely cross the PM independently of membrane transport proteins.
• Water-soluble molecules require membrane transport proteins in order to cross the PM.

Question 14

Permeability

Answer 14

Permeability through a synthetic lipid bilayer is determined by:

• molecular size
• electrical charge
• lipid-solubility of the molecule
• hydrophobicity or hydrophilicity

Protein-free lipid bilayers are highly impermeable to ions, and large, uncharged, polar molecules such as glucose.

Question 15

Why Can’t Ions Pass?

Answer 15

Ions such as Sodium (Na+) ions are surrounded by water molecules that form a ‘sphere of hydration’ or ‘Hydration Shell’ around them.

Water molecules (H2O) are polar molecules. The oxygen atom (red) of a water molecule has a partial negative charge and it is therefore electrostatically attracted to Na+ ions (grey), which are positively charged cations.

The hydrogen atoms (white) of a water molecule have a partial positive charge and are electrostatically attracted to the oxygens of other water molecules.

Because of their watery hydration shells, Sodium (Na+) and Chloride (Cl-) ions (and other ions) cannot get across the plasma membrane simply by diffusing directly through the lipid bilayer.

Ions and other water-soluble molecules can move across cell membranes only by moving through membrane transport proteins that shield them from contact with the hydrophobic hydrocarbon tails of membrane phospholipids.

Question 16

Membrane Transport Proteins

Answer 16

Membrane transport proteins are proteins that are embedded within the phospholipid bilayer of the plasma membrane.

Ion Channels

Pumps (aka ATPases)

Exchangers (aka Antiporters)

Co-transporters (aka Symporters)

Uniporters

Question 17

Ion Channels

Answer 17

Ions require membrane proteins to traverse the lipid bilayer.

Ion channels are transmembrane proteins that conduct ions at high rates.

They contain an aqueous pore that is shielded from contact with the bilayer.

They may possess gates that can be open or closed.

They may be highly selective for a particular ion species (have selectivity filter, a pinch point).

They mediate passive transport driven by simple diffusion.

Question 18

Gating Mechanisms of ion Channels

Answer 18

Voltage-gated = closed with plus to plus and open with plus to minus

Ligand-gated (extracellular ligand) - basically lock and key structure

Ligand-gated (intracellular ligand) - lock and key on the inside

Mechanically gated - moved mechanically (physically)

Question 19

Transporters

Answer 19

Are membrane proteins that transport various solutes across lipid bilayers.

They bind their solute MORE STRONGLY (i.e., with higher affinity) than channels but MORE WEAKLY than pumps.

Their rate of transport is slower than channels.

Their FLUX RATE is 102 to 104 ions/sec.

They alternatively toggle between two (2) or more conformations.

Their solute-binding site or sites are alternately exposed on opposite sides of the bilayer.

They have to change their conformation every time they transport their substrates across the cell membrane.

Transporters may toggle between two or more conformations. (outward-open to occluded to inward-open)

The solute-binding site is ALTERNATELY EXPOSED on opposite sides of the bilayer.

Question 20

Passive Transport

Answer 20

In passive transport, the solute moves along its electrochemical gradient. No energy required.

Question 21

Electro-Chemical gradient

Answer 21

An Electro-Chemical gradient is the net sum of the electrical gradient and the chemical (or concentration) gradient.

NOTE: Electrical gradients and electrochemical gradients only apply to charged solutes like Na+ and Cl-.

Question 22

Passive Transport - Example

Answer 22

Example: ion channels, passive transporters (e.g., GLUT) or simple diffusion through lipid bilayer.

Question 23

Active Transport

Answer 23

In active transport, the solute moves against its electrochemical gradient.

• Active transport is mediated by transporters coupled to energy source.
• Active transport requires energy input, either directly or indirectly.

Question 24

Primary Active Transport

Answer 24

solutes are transported against their chemical (concentration) or electrochemical gradient by a transporter protein (pump) that consumes energy.

Example: Na+/K+ ATPase (aka the Na+ pump)

Question 25

Secondary Active Transport

Answer 25

solutes are transported against their chemical (concentration) or electrochemical gradient using a concentration or electrochemical gradient established by a pump. Examples: Na+/Ca2+ exchanger, and Na+/glucose symporter

Question 26

Pumps/ATPases

Answer 26

Pump proteins (which mediate primary active transport) establish the electrochemical gradients of ions by using energy to pump ions across the bilayer. Pump proteins are enzymes - usually they are ATPases.

Question 27

Coupled-Transport

Answer 27

Coupled-transport proteins (which mediate secondary active transport) rely upon the potential energy stored in the electrochemical gradient for an ion. Coupled-transport proteins usually are not enzymes (they are toggle proteins).

Question 28

Uniporter

Answer 28

one molecular substrate is transported.

Question 29

Two types of coupled transporter proteins:

Answer 29

Symporter: two molecular substrates – each transported in the SAME direction. Antiporter: two molecular substrates – each transported in OPPOSITE directions.

Question 30

Primary Active – Example Na+/K+ Pump

Answer 30

Maintains osmotic balance and stabilizes cell volume by controlling intracellular [Na+] at lower concentrations. The Na+-K+ pump is an ATPase enzyme that cleaves ATP into ADP and attaches a phosphate molecule (P) to itself in order to drive changes in its shape (= autophosphorylation).

Question 31

Osmosis

Answer 31

diffusion of water down its concentration gradient.

Question 32

Osmolarity (or tonicity)

Answer 32

a term used to describe the concentration of a solute in terms of the osmotic pressure it can exert

Question 33

Hypertonic solution

Answer 33

an introduced cell will lose water and shrink

Question 34

Hypotonic solution

Answer 34

cell will gain water and swell (& maybe burst)

Question 35

Blocking the Na+-K+ pump:

Answer 35

It can be blocked by plant compounds (Ouabain (binds to K+-binding site), Digitalis, and Convallaria)

Question 36

The pumping cycle of the Na+-K+ ATPase

Answer 36

1) Three intracellular Na+ ions bind to the pump and trigger Na-dependent autophosphorylation. One ATP is consumed during autophosphorylation of the pump protein. 2) Phosphorylation triggers a change in pump conformation, ejecting the 3 Na+ ions to the extracellular solution. 3) Two extracellular K+ ions bind the pump, triggering K-dependent dephosphorylation. 4) Dephosphorylation triggers release of 2 K+ into the cytosol.

Question 37

Purple Foxglove - Digoxin (Digitalis purpurea)

Answer 37

As a medicine: * ‘Discovered’ in 1775 by William Withering, a rich Scottish MD (his girlfriend was an amateur botanist). Patient w/congestive heart failure and dropsy. * No effective allopathic treatment at that time. * Herbal remedy – mixture of powdered leaves – active component was isolated. * Foxglove plant contains important cardiac glycosides including digitoxin, digoxin and others. * These drugs are used in modern medicine to treat congestive heart failure. * They affect cardiac function by inhibiting the Na+-K+ ATPase.

Question 38

Inhibiting the Na+-K+ ATPase has the following effects:

Answer 38

It produces a decrease in intracellular [K+] and an increase in intracellular [Na+]. The increase in intracellular [Na+] decreases the electrochemical gradient driving Na+ ions into the cytosol. This reduces the efficiency of an important secondary active transporter protein known as the Na+/Ca2+ exchanger, responsible for ejecting Ca2+ from the cytosol. This results in an increase in resting intracellular [Ca2+], which increases the force of systolic contractions and prolongs the duration of the diastolic phase (resulting in more ventricular filling), thus producing an increase in cardiac output (i.e., this is a positive inotropic effect).

Question 39

Example of Coupled Transport:

Answer 39

Transport of glucose against its concentration gradient can be driven by an electrochemical gradient for sodium ions (Na+), established by the Na+ pump.

Question 40

Na+/glucose cotransporter:

Answer 40

the electrochemical gradient for Na+ drives a conformational change in a co-transporter (symporter) that results in glucose transport uphill against its concentration gradient.

Question 41

Transport of Glucose

Answer 41

Transepithelial transport of glucose across the intestinal epithelium requires: 1) an electrochemical gradient for Na+ 2) differential localization of several different transport proteins in different domains of the plasma membrane (apical and basolateral membranes).

Question 42

Ion Concentrations

Answer 42

Concentrations of the major physiological ions are very different between the intracellular & extracellular fluids. These differences are established and maintained by active transport processes that consume metabolic energy (ATP).