Transport of molecules

Question 1

Types of movement across a membrane

Answer 1

-Passive (with concentration gradient):
- diffusion
- facilitated diffusion: ion channels (uniporter) & carrier-mediated transport

-Active (against concentration gradient):
- Primary active (pumps)
- Secondary active (cotransport) e.g. symporter and antiporter
- Vesicular transport

Question 2

Diffusion flux

Answer 2

Question 3

What factors affect the rate of diffusion?

Answer 3

• Temperature
• Surface area
• The medium through which the molecules are moving
• Concentration gradient
• Solubility of molecule
• 1/Size of molecule (mol. wt)
• 1/distance squared

Question 4

Is energy involved in diffusion?

Answer 4

• The random thermal motion of molecules in a liquid or gas will eventually distribute them uniformly throughout a container.

-This is the second law of thermodynamics, which states that a closed (isolated) system will always tend toward maximum entropy, or disorder.

• Thus, if we start with a solution in which a solute is more concentrated in one region than another, random thermal motion will redistribute the solute from regions of higher concentration to regions of lower concentration until the solute reaches a uniform concentration throughout the solution.
• This movement of molecules from one location to another solely as a result of their random thermal motion is known as simple diffusion.

Question 5

What is a flux?

Answer 5

The amount of material crossing a surface in a unit of time

Question 6

Concentration of molecules vs rate of diffusion

Answer 6

If the number of molecules in a unit of volume is doubled, the flux of molecules across the surface of the unit will also be doubled because twice as many molecules will be moving in any direction at a given time.

Question 7

What is the net flux?

Answer 7

• The net flux of glucose between the two compartments at any instant is the difference between the two one-way fluxes.
• The net flux determines the net gain of molecules in compartment 2 per unit time and the net loss from compartment 1 per unit time.

Question 8

Diffusion equilibrium

Answer 8

• Eventually, the concentrations of glucose in the two com- partments become equal at 10 mmol/L.
• Glucose molecules continue to move randomly, and some will find their way from one compartment to the other.
• However, the two one-way fluxes are now equal in magnitude but opposite in direction; therefore, the net flux of glucose is zero (see Figure 4.2, time C). The system has now reached diffusion equilibrium.

Question 9

Diagram showing diffusion of glucose between two compartments of equal volume separated by a barrier permeable to glucose.

Answer 9

Question 10

Effect of temperature on rate of diffusion

Answer 10

The more elevated the temperature, the greater the speed of molecular movement and the faster the net flux

Question 11

Effect of mass of the molecule on rate of diffusion

Answer 11

Large molecules such as proteins have a greater mass and move more slowly than smaller molecules such as glucose and, consequently, have a slower net flux

Question 12

Effect of surface area on rate of diffusion

Answer 12

Surface area—the greater the surface area separating two regions, the greater the space available for diffusion and, therefore, the faster the net flux

Question 13

Effect of the medium through which the molecules are moving on rate of diffusion

Answer 13

Molecules diffuse more rapidly in air than in water. This is because collisions are less frequent in a gas phase.

Question 14

Diffusion rate vs. distance

Answer 14

• Although individual molecules travel at high speeds, the number of collisions they undergo prevents them from traveling very far in a straight line.
• Diffusion times increase in proportion to the square of the distance over which the molecules diffuse. Thus, although diffusion equilibrium can be reached rapidly over distances of cellular dimensions, it takes a very long time when distances of a few centimeters or more are involved.
• For an organism as large as a human being, the diffusion of oxygen and nutrients from the body surface to tissues located only a few centimeters below the surface would be far too slow to provide adequate nourishment.

-This is overcome by the circulatory system, which provides a mechanism for rapidly moving materials over large distances using a pressure source (the heart). This process, known as bulk flow.

• Diffusion, on the other hand, provides movement over the short distances between the blood, inter-stitial fluid, and intracellular fluid.

Question 15

What effects do membranes have on diffusion?

Answer 15

• The rate at which a substance diffuses across a plasma membrane can be measured by monitoring the rate at which its intracellular concentration approaches diffusion equilibrium with its concentration in the extracellular fluid.
• For simplicity’s sake, assume that because the volume of extracellular fluid is large, its solute concentration will remain essentially constant as the substance diffuses into the intracellular fluid.
• As with all diffusion processes, the net flux of material across the membrane is from the region of greater concentration (the extra-cellular solution in this case) to the region of lower concentration (the intracellular fluid).

Question 16

Diffusion equation and permeability coefficient

Answer 16

Question 17

More info on equation?

Question 18

Diffusion through the lipid bilayer

Answer 18

• When the permeability coefficients of different organic molecules are examined in relation to their molecular structures, a correlation emerges.
• Whereas most polar molecules diffuse into cells very slowly or not at all, nonpolar molecules diffuse much more rapidly across plasma membranes—that is, they have large permeability coefficients.

Question 19

Why do polar and non-polar molecules diffuse across the lipid bilayer differently?

Answer 19

• Non-polar molecules can dissolve in the non-polar regions of the membrane occupied by the fatty acid chains of the membrane phospholipids.
• In contrast, polar molecules have a much lower solubility in the membrane lipids.

Question 20

Weak acids and permeability

Answer 20

• The distribution of weak electrolytes across membranes would result from the pH gradient across the membrane and the drug’s pKa.
• Weakly acidic drugs are easily absorbed in a low pH medium such as in the stomach.
• Whereas weakly basic drugs are not absorbed until they reach the higher pH medium in the small intestine.”
• Permeability of weak acids and bases changes when protonated or not protonated.

Question 21

pH Gradient and permeability of weak acids in stomach

Answer 21

• A weak acid can be protonated (A- + H+  HA) or unprotonated HA+  A- + H+
  When unprotonated it is ionized, A-, and is non-permeable.
• When protonated it is non-ionized, HA, and is permeable because it is lipophilic.
• If a pH gradient exists across a membrane, more of the molecule will be protonated on the side that is more acidic, lower pH, higher concentration of H+
• This standing pH gradient will drive the diffusion of the molecule from the side that favors the more permeable form towards the side that does not favor the more permeable form

Question 22

Weak acids are permeable when ___

Answer 22

Protonated

Question 23

Weak bases are permeable when ___

Answer 23

Unprotonated

Question 24

How is the pH of the stomach maintained?

Answer 24

• pH in stomach lumen maintained by secretion of HCl
• pH inside of cells maintained by active processes (H+ transport; buffers)
• Small amount of weak acid drugs added to this ocean of fluid

Question 25

Ion channels

Answer 25

Proteins that form a pore in the membrane

Selectivity:
- Can be selectively permeable to single ion

Permeability:
- Extremely permeable (conducts ions at very fast rate)

Gating:
-Can be opened and closed
- Mechanically gated (stretch receptors)
- Voltage gated (VG Na+ channels)
- Ligand gated (acetylcholine receptors)

Question 26

Selectivity of ion channels

Answer 26

• An important characteristic of ion channels is that they can show selectivity for the type of ion or ions that can diffuse through them.
• This selectivity is based on the channel diameter, the charged and polar surfaces of the polypeptide subunits that form the channel walls and electrically attract or repel the ions, and the number of water molecules associated with the ions (so-called waters of hydration).
• For example, some channels (K+ channels) allow only potassium ions to pass, whereas oth- ers are specific for sodium ions (Na+ channels).
• For this reason, two membranes that have the same permeability to K+ because they have the same number of K+ channels may nonetheless have quite different+permeabilities to Na+ if they contain different numbers of Na channels.

Question 27

When describing the diffusion of ions, because they are charged, one additional factor must be considered: ___

Answer 27

The presence of electrical forces acting upon the ions.

Question 28

Membrane potential?

Question 29

Potassium Channels video

Answer 29

https://www.youtube.com/watch?v=lnKIBZYarzM

Question 30

How an ion permeates a channel

Answer 30

• Each ion is surrounded by water molecules forming a sphere of hydration.
• Positive ions attract partial negative Oxygen
• The geometry of this sphere is different for each ion
  Na-O distance = 2.4 A vs
  K-O distance = 2.73 A
• The aqueous pore of a Na+ selective ion channel has the same geometry of negative partial charges of the sphere of hydration.
• Water molecules are removed from ion as it goes through pore

Question 31

Carrier-mediated transport overview

Answer 31

Facilitated Diffusion (no energy; down gradient)
- Selectivity
- Permeability (relatively slow, but still fast)
- Saturability
- Competition

Active Transport (energy needed; up gradient)
- Selectivity
- Permeability (relatively slow, but still fast)
- ATP dependent

Question 32

Characteristics of carrier and active transport

Answer 32

• Specificity – transport protein recognizes specific molecules with specific physical properties
• Saturability – the rate of transport can reach a plateau (Transport max or T max) if concentration of transported molecule is high and number of transport proteins is small
• Competition – structurally similar molecules may compete for access to transport protein

Question 33

Primary and secondary active transport

Answer 33

• a particle is going “up” or “against” a gradient
- an energy source is required e.g. ATP

Primary Active
- ATP powering the movement against a concentration gradient is utilized by the transport protein (e.g. pumps)

Secondary Active
- ATP powering the movement against a concentration gradient is utilize at a different location than the transport protein (e.g. cotransporters)

Question 34

Vesicular Transport

Answer 34

Endocytosis
- Pinocytosis
- Phagocytosis

Exocytosis
- Secretory vesicles
- Synaptic vesicles

Question 35

Regulation of diffusion through ion channels?

Question 36

What happens when transporters are saturated?

Answer 36

• The maximal transport flux depends upon the rate at which the conformational changes in the transporters can transfer their binding sites from one surface to the other.
• This rate is much slower than the rate of ion diffusion through ion channels.

Question 37

Diagram of mediated transport

Answer 37

Question 38

Graph showing the flux of molecules diffusion into a cell across the lipid bilayer of a plasma membrane (green line) increases continuously in proportion to the extracellular concentration, whereas the flux of molecules through a mediated-transport system (purple line) reaches a maximal value

Answer 38

Question 39

What provides the energy for primary active transport?

Answer 39

• The hydrolysis of ATP by a transporter
• The transporter itself is an enzyme called ATPase that catalyzes the breakdown of ATP and, in the process, phosphorylates itself.

-Phosphorylation of the transporter protein is a type of covalent modulation that changes the conformation of the transporter and the affinity of the transporter’s solute binding site.

Question 40

Example of primary active transport- sodium-potassium pump

Answer 40

Question 41

Secondary active transport

Answer 41

• In secondary active transport, the movement of an ion down its electrochemical gradient is coupled to the transport of another molecule, often an organic nutrient like glucose or an amino acid.
• Thus, transporters that mediate secondary active transport have two binding sites, one for an ion—typically but not always Na+—and another for a second substance.

Question 42

Example of secondary active transport

Answer 42

• In this example, the binding of a sodium ion to the transporter produces an allosteric increase in the affinity of the solute binding site at the extracellular surface of the membrane.
• Binding of Na+ and solute causes a conformational change in the transporter that exposes the binding sites to the intracellular fluid.
• Na+ diffuses down its electrochemical gradient into the cell, which returns the solute binding site to a low-affinity state.

Question 43

Symport and antiport/cotransport and countertransport

Answer 43

• The movement of the actively transported solute can be either into the cell (in the same direction as Na+), in which case it is known as cotransport, or out of the cell (opposite the direction of Na+ movement), which is called countertransport.
• The terms symport and antiport are also used to refer to the processes of cotransport and countertransport, respectively.
• In summary, the distribution of substances between the intracellular and extracellular fluid is often unequal due to the presence in the plasma membrane of primary and secondary active transporters, ion channels, and the membrane potential.

Question 44

Table summarizing types of movement across membranes

Answer 44

Question 45

What are aquaporins?

Answer 45

• Water is a polar molecule and yet it diffuses across the plasma membranes of most cells very rapidly.
• This process is mediated by a family of membrane proteins known as aquaporins that form channels through which water can diffuse.
• The type and number of these water channels differ in different membranes. Consequently, some cells are more permeable to water than others.
• Furthermore, in some cells, the number of aquaporin channels—and, therefore, the permeability of the membrane to water—can be altered in response to various signals.

Question 46

How adding a solute affects the concentration of water- math

Answer 46

• A liter of pure water weighs about 1000 g, and the molecular weight of water is 18.
• Thus, the concentration of water molecules in pure water is 1000/18 = 55.5 M.
• The decrease in water concentration in a solution is approximately equal to the concentration of added solute.
• In other words, one solute molecule will displace one water molecule. The water concentration in a 1 M glucose solution is therefore approximately 54.5 M rather than 55.5 M.

Question 47

What does the degree to which the water concentration is decreased by the addition of solute depend on?

Answer 47

• The number of particles (molecules or ions) of solute in solution (the solute concentration) and not upon the chemical nature of the solute.
• For example, 1 mol of glucose in 1 L of solution decreases the water concentration to the same extent as does 1 mol of an amino acid, or 1 mol of urea, or 1 mol of any other molecule that exists as a single particle in solution.
• On the other hand, a molecule that ionizes in solution decreases the water concentration in proportion to the number of ions formed.
• For example, many simple salts dissociate nearly completely in water. For simplicity’s sake, we will assume the dissociation is 100% at body temperature and at concentrations found in the blood.
• Therefore, 1 mol of sodium chloride in solution gives rise to 1 mol of sodium ions and 1 mol of chloride ions, producing 2 mol of solute particles.
• This decreases the water concentration twice as much as 1 mol of glucose.
• By the same reasoning, if a 1 M MgCl2 solution were to dis- sociate completely, it would decrease the water concentration three times as much as would a 1 M glucose solution.

Question 48

Diffusion summary

Answer 48

I. Simple diffusion is the movement of molecules from one location to another by random thermal motion.
a. The net flux between two compartments always proceeds from
higher to lower concentrations.
b. Diffusion equilibrium is reached when the concentrations of the
diffusing substance in the two compartments become equal.

II. The magnitude of the net flux J across a membrane is directly
proportional to the concentration difference across the membrane Co − Ci, the surface area of the membrane A, and the membrane permeability coefficient P.

III. Nonpolar molecules diffuse through the hydrophobic portions of membranes much more rapidly than do polar or ionized molecules because nonpolar molecules can dissolve in the fatty acyl tails in the lipid bilayer.

IV. Ions diffuse across membranes by passing through ion channels formed by integral membrane proteins.
a. The diffusion of ions across a membrane depends on both the
concentration gradient and the membrane potential.
b. The flux of ions across a membrane can be altered by opening
or closing ion channels.

Question 49

Mediated-transport systems summary

Answer 49

I. The mediated transport of molecules or ions across a membrane involves binding the transported solute to a transporter protein in the membrane. Changes in the conformation of the transporter move the binding site to the opposite side of the membrane, where the solute dissociates from the protein.
a. The binding sites on transporters exhibit chemical specificity, affinity, and saturation.
b.The magnitude of the flux through a mediated transport system depends on the degree of transporter saturation, the number
of transporters in the membrane, and the rate at which the conformational change in the transporter occurs.

II. Facilitated diffusion is a mediated transport process that moves molecules from higher to lower concentrations across a membrane using a transporter until the two concentrations become equal. Metabolic energy is not required for this process.

III. Active transport is a mediated transport process that moves molecules against an electrochemical gradient across a membrane through a transporter and an energy input.
a. Primary active transport uses the phosphorylation of the
transporter by ATP to drive the transport process. +
b. Secondary active transport uses the binding of ions (often Na )
to the transporter to drive the secondary-transport process.
c. In secondary active transport, the downhill flow of an ion
is linked to the uphill movement of a second solute either in the same direction as the ion (cotransport) or in the opposite direction of the ion (countertransport).

Question 50

Osmosis summary

Answer 50

I. Water crosses membranes by (a) diffusing through the lipid bilayer, and (b) diffusing through protein channels in the membrane.

II. Osmosis is the diffusion of water across a membrane from a
region of higher water concentration to a region of lower water concentration. The osmolarity—total solute concentration in a solution—determines the water concentration: The higher the osmolarity of a solution, the lower the water concentration.

III. Osmosis across a membrane that is permeable to water but impermeable to solute leads to an increase in the volume of the compartment on
the side that initially had the higher osmolarity, and a decrease in the volume on the side that initially had the lower osmolarity.

IV. Application of sufficient pressure to a solution will prevent the osmotic flow of water into the solution from a compartment of pure water. This pressure is called the osmotic pressure. The greater the osmolarity of a solution, the greater its osmotic pressure. Net water movement occurs from a region of lower osmotic pressure to one of higher osmotic pressure.

V. The osmolarity of the extracellular fluid is about 300 mOsm. Because water comes to diffusion equilibrium across cell membranes, the intracellular fluid has an osmolarity equal to that of the extracellular fluid.
a. Na+ and Cl− are the major effectively nonpenetrating solutes in the extracellular fluid; K+ and various organic solutes are the major effectively nonpenetrating solutes in the intracellular fluid.

Question 51

Some equations combine solubility and molecular size of the molecule into the term ___

Answer 51

Permeability