Membrane Physiology Ion Channels and Transport

Question 1

What stabilizes the tm proteins in the lipid bilayer

Question 2

Transport of molecules across the cell membrane
•Membranes form hydrophobic barriers around cells and restrict the entry and exit of molecules

• This barrier function is crucially important because it allows the cell to____ ____of solutes in its cytosol that are different from those in the ___ ___ and in each of the ____ ____-enclosed compartments
• However, because of the barrier property of the membrane, cells require transport systems to permit entry and exit of
• ____ ___ ____that they need (___)
• concentrate compounds inside the cell (__)
• expel compounds out of the cell (__)

•A large number of genes encode for transport proteins, which make up between ______% of the membrane proteins. Some specialized mammalian cells devote up to ____ of their total metabolic energy consumption to membrane transport processes.•
•

Answer 2

•Membranes form hydrophobic barriers around cells and restrict the entry and exit of molecules
•
•This barrier function is crucially important because it allows the cell to maintain concentrations of solutes in its cytosol that are different from those in the extracellular fluid and in each of the intracellular membrane-enclosed compartments
•
•However, because of the barrier property of the membrane, cells require transport systems to permit entry and exit of

• small polar compounds that they need (glucose)
• concentrate compounds inside the cell (K+)
• expel compounds out of the cell (Ca2+ and Na+)

•A large number of genes encode for transport proteins, which make up between 15 and 30% of the membrane proteins. Some specialized mammalian cells devote up to two-thirds of their total metabolic energy consumption to membrane transport processes.•
•
•
•
•
•

Question 3

Let’s consider transport across protein-free lipid bilayer

Permeability coefficients for the passage of various molecules through synthetic lipid bilayers. Unit is cm/sec.

•Given enough ___, virtually any molecule will diffuse across a___ ___lipid bilayer___ its concentration gradient – BUT the ___ at which it does so will vary enormously depending on, (1) ___of molecule, and (2) ____ ____ of molecule in oil

•Small non-polar molecules (___, ___) readily ___ in lipid bilayer and ___ ___across them
•Small uncharged polar molecules (___,___), also diffuse across lipid bilayer but at a ___ rate
•Larger uncharged polar molecules (___,___) are very ___ lipid soluble and therefore diffuse very ____
•No matter how small, lipid bilayers are ___e to ____molecules (ions). Charge and high degree of ___ of such molecules prevent them from entering the lipid bilayer
•Therefore, special membrane transport proteins are required for transferring __ ___and ___solutes across the cell membrane!
•

Answer 3

Permeability coefficients for the passage of various molecules through synthetic lipid bilayers. Unit is cm/sec.

•Given enough time, virtually any molecule will diffuse across a protein-free lipid bilayer down its concentration gradient – BUT the rate at which it does so will vary enormously depending on, (1) size of molecule, and (2) relative solubility of molecule in oil

• Small non-polar molecules (O2, CO2) readily dissolve in lipid bilayer and diffuse rapidly across them
• Small uncharged polar molecules (water, urea), also diffuse across lipid bilayer but at a slower rate
• Larger uncharged polar molecules (glucose, sucrose) are very sparingly lipid soluble and therefore diffuse very slowly

•No matter how small, lipid bilayers are impermeable to charged molecules (ions). Charge and high degree of hydration of such molecules prevent them from entering the lipid bilayerà because of the charge
•Therefore, special membrane transport proteins are required for transferring large uncharged and charged solutes across the cell membrane!
•

Question 4

Transport of molecules across the plasma membrane

•The transport systems for ___ ____ molecules and ___ ions fall into 3 categories

1.

2.

3.

Note - Fourth mechanism of transport used for the transport of ___ ___ molecules is ___

•Simple diffusion is the ___ flow of a solute from a ___ to a ___ concentration (downhill) due to ___ ____ ____.
•
•Facilitated diffusion is ___ transport of a solute from ___ to a ___ concentration (downhill) mediated by a specific __ ___.
•
•Active transport is transport of a solute across a membrane ___ a concentration gradient (uphill), and thus requires ___ (frequently derived from the ___ of ___); a specific _____(pump) is involved. Active transport can be further subdivided into ____and___ active transport.

Answer 4

•The transport systems for small organic molecules and inorganic ions fall into 3 categories

1. Simple diffusion
2. Facilitated Diffusion
3. Active transport

Note - Fourth mechanism of transport used for the transport of large individual molecules is endocytosis
•Simple diffusion is the passive flow of a solute from a higher to a lower concentration (downhill) due to random thermal movement.
•
•Facilitated diffusion is passive transport of a solute from a higher to a lower concentration (downhill) mediated by a specific protein transporter.
•
•Active transport is transport of a solute across a membrane against a concentration gradient (uphill), and thus requires energy (frequently derived from the hydrolysis of ATP); a specific transporter (pump) is involved. Active transport can be further subdivided into primary and secondary active transport.

Question 5

Concentration (chemical) gradient vs Electrochemical gradient

• In the case of uncharged molecules, movement of the molecule is influenced by its ____ gradient.
• In the case of charged molecules, movement across a membrane is influenced by the molecule’s ___gradient, and by the fact that the interior of the plasma membrane is ___charged relative to the extracellular side of the membrane. This negative membrane potential exerts a force on any molecule carrying an electrical charge, which determines an electrical gradient (or ___ ___ ___) for that molecule. The effects of the electrical and concentration gradients of a molecule are combined in what is called the ____ gradient transport.

Answer 5

• In the case of uncharged molecules, movement of the molecule is influenced by its concentration gradient.
• In the case of charged molecules, movement across a membrane is influenced by the molecule’s concentration gradient, and by the fact that the interior of the plasma membrane is negatively charged relative to the extracellular side of the membrane. This negative membrane potential exerts a force on any molecule carrying an electrical charge, which determines an electrical gradient (or electrical energy difference) for that molecule. The effects of the electrical and concentration gradients of a molecule are combined in what is called the electrochemical gradient transport.

Question 6

Simple Diffusion

____ (such as O2 and CO2), and ___ ___ substances (such as steroid hormones) cross membranes by simple diffusion.
•
•In simple diffusion, small uncharged molecules move from region of high concentration to region of low concentration – can occur from extracellular side to intracellular side or ___ ____ depending on concentration gradient. Movement occurs until the ____ ____ is achieved on __ ___of the membrane.

Answer 6

•Gases (such as O2 and CO2), and lipid-soluble substances (such as steroid hormones) cross membranes by simple diffusion.
•
•In simple diffusion, small uncharged molecules move from region of high concentration to region of low concentration – can occur from extracellular side to intracellular side or vice versa depending on concentration gradient. Movement occurs until the same concentration is achieved on both sides of the membrane.

Question 7

Simple Diffusion

•The following factors affect net diffusion of a substance
•

(1) Its ___ ____across the membrane: solutes move from high

to low concentration

(2) The____ ____ of the substance for the membrane – Its solubility in the lipid bilayer

(3) The ___ ____ gradient across the membrane: increased pressure will increase the ___ and ___of the collision between the ___ and the ___
(4) Temperature: increased temperature will increase particle ___ and thus increase the ____ of collisions between external particles and the membrane

•
•Diffusion kinetics is ___ – not ___
•
•No ___ required.
•
•No ____ involved.

Answer 7

•The following factors affect net diffusion of a substance
•

(1) Its concentration gradient across the membrane: solutes move from high

to low concentration

(2) The permeability coefficient of the substance for the membrane – Its

solubility in the lipid bilayer

(3) The hydrostatic pressure gradient across the membrane: increased

pressure will increase the rate and force of the collision between the

molecules and the membrane

(4) Temperature: increased temperature will increase particle motion and

thus increase the frequency of collisions between external particles and the

membrane

•
•Diffusion kinetics is linear – not saturable.
•
•No energy required.
•
•No protein involved.

Question 8

Facilitated Diffusion

•Facilitated diffusion requires carrier or channel protein to ____ move polar or charged molecules
•
•Carrier or channel proteins are ____ ____proteins that enable specific hydrophillic solutes to cross the membrane without coming into direct contact with the hydrophobic interior of the lipid bilayer

•
•The mechanism is ___ diffusion – ie., the molecule moves from a region of high concentration to one of low concentration and therefore can occur in either direction depending on concentration gradient.
•
•Energy is ___ ____

Answer 8

•Facilitated diffusion requires carrier or channel protein to selectively move polar or charged molecules
•
•Carrier or channel proteins are multipass transmembrane proteins that enable specific hydrophillic solutes to cross the membrane without coming into direct contact with the hydrophobic interior of the lipid bilayer

•
•The mechanism is passive diffusion – ie., the molecule moves from a region of high concentration to one of low concentration and therefore can occur in either direction depending on concentration gradient.
•
•Energy is not required

Question 9

Carrier-mediated diffusion

•Carriers – also known as ___ or ____
•
•Carrier-mediated diffusion requires ____ binding of molecules to be transported to the carrier
•
•The molecule binds on one side of the membrane, following which the carrier protein undergoes ____ changes that allow the molecule to pass through the membrane and be released on the other side.
•
•Although the transported molecules are bound to proteins, the transport process is still classified as diffusion because energy is not required, and the compound ____
•
___ ___ and ____ are transported by carriers.
•
•What would kinetics of transport by carrier proteins look like? Clue – carrier proteins, like enzymes, exhibit saturation kinetics.

Answer 9

•Carriers – also known as permeases or transporters
•
•Carrier-mediated diffusion requires specific binding of molecules to be transported to the carrier
•
•The molecule binds on one side of the membrane, following which the carrier protein undergoes conformational changes that allow the molecule to pass through the membrane and be released on the other side.
•
•Although the transported molecules are bound to proteins, the transport process is still classified as diffusion because energy is not required, and the compound equilibrates.
•
•Sugars, amino acids and nucelosides are transported by carriers.
•
•What would kinetics of transport by carrier proteins look like? Clue – carrier proteins, like enzymes, exhibit saturation kinetics.

Question 10

Kinetics of simple vs carrier-mediated diffusion

•The rate at which solutes enter a cell by carrier-mediated diffusion is determined not only by the ___ ___ of solute across the membrane but also by the ___ of carrier proteins available.
•
•Therefore, carrier-mediated diffusion resembles ___ ____ interaction.
•
•Points of resemblance to enzyme action are as follows:

(1) There is a ___ ___ ___ for the solute
(2) The carrier is ____e, so it has a maximum ___of

transport (Vmax)

(3) There is a___ ____

(Km) for the solute

(4) Structurally similar ___ ___ ____transport

Answer 10

•The rate at which solutes enter a cell by carrier-mediated diffusion is determined not only by the concentration gradient of solute across the membrane but also by the amount of carrier proteins available.
•
•Therefore, carrier-mediated diffusion resembles substrate–enzyme interaction.
•
•Points of resemblance to enzyme action are as follows:

(1) There is a specific binding

site for the solute

(2) The carrier is saturable, so it

has a maximum rate of

transport (Vmax)

(3) There is a binding constant

(Km) for the solute

(4) Structurally similar

competitive inhibitors block

transport

Question 11

Example of carrier-mediated diffusion: Glucose transporter
•Glucose cannot cross membrane readily in absence of transporter
•Family of transport proteins (____-___) encoded by ____ genes with different____ ____ have been identified
_____changes in the transporter accompany glucose movement across the membrane

• In the first conformation shown (A), glucose binds to a site exposed on the ____ of the plasma membrane. The transporter then undergoes a ____change such that the glucose-binding site faces the ____of the cell and glucose is released into the ____(B). The transporter then returns to its ____ conformation (C).
• Competitive inhibition by glucose ____
• Stereospecific for___glucose

Answer 11

• Glucose cannot cross membrane readily in absence of transporter
• Family of transport proteins (GLUT1-GLUT7) encoded by different genes with different tissue distributions have been identified
• Conformational changes in the transporter accompany glucose movement across the membrane
• In the first conformation shown (A), glucose binds to a site exposed on the outside of the plasma membrane. The transporter then undergoes a conformational change such that the glucose-binding site faces the inside of the cell and glucose is released into the cytosol (B). The transporter then returns to its original conformation (C).
• Competitive inhibition by glucose analogsà bind to same sight
• Stereospecific for D-glucose

Question 12

Channel-mediated diffusion

•Channels transport____( _ _ _ _).
•
•Most channels are____ – the____ pore of an ion channel is not ___ ____
•
•The channel switches between an ___ and ___ state by a change in conformation, regulated by a _____
•
•The stimuli can be ____changes across the membrane (______ channels), the ____of a compound ____ gated channels), or a ____ change in the ____ domain (____-gated and ____ gated).
•
•There is ___ ____ of molecule to be transported to the channel - channel proteins form open pores through the membrane, allowing the free diffusion of any molecule of the appropriate ___and ____– therefore, facilitated diffusion by channels is much ____ than by carriers.
•
•Channels are____ too - selectivity is determined by the____ of the central ___ and the distribution of ___ ___ ___ along the outside of a channel’s opening.

Answer 12

•Channels transport ions (Na+, K+, Ca2+, Cl-).
•
•Most channels are gated – the central pore of an ion channel is not continuously open.
•
•The channel switches between an open and closed state by a change in conformation, regulated by a stimulus.
•
•The stimuli can be voltage changes across the membrane (voltage-gated channels), the binding of a compound (ligand-gated channels), or a regulatory change in the intracellular domain (phosphorylation-gated and pressure-gated).
•
•There is no binding of molecule to be transported to the channel - channel proteins form open pores through the membrane, allowing the free diffusion of any molecule of the appropriate size and charge – therefore, facilitated diffusion by channels is much faster than by carriers.
•
•Channels are selective too - selectivity is determined by the size of the central pore and the distribution of charged amino acids along the outside of a channel’s opening.

Question 13

Example of channel-mediated diffusion: Nicotinic Acetylcholine Receptor

•Binding of ___molecules induces a ___ ___ that leads to ___ of the transmembrane channel allowing diffusion of ____ ions through the conducting pore
•
___ of positive ions into the cells leads to ____, which could result in the generation of action potential (we will learn about this in the next lecture)
•
•Continued presence of ____ results in a ____ conformational change where the channel ___ and the protein enters a _____ state
•
•

Answer 13

•
•Binding of ACh molecules induces a conformational change that leads to opening of the transmembrane channel allowing diffusion of Na+ ions through the conducting pore
•
•Influx of positive ions into the cells leads to depolarization, which could result in the generation of action potential (we will learn about this in the next lecture)
•
•Continued presence of agonist results in a second conformational change where the channel closes and the protein enters a desensitized state
•
•

Question 14

Active Transport

•Transport of a molecule ____ its gradient is energetically unfavorable, and therefore requires that the transporter harness an energy source.
•
•If energy is applied directly to the transporter (through hydrolysis of ATP), the transport is called _____ active transport; if the energy is used to establish an ___ ____ and the gradient is used to___ another compound, the transport is called ____ active transport.
•
•Depending on the transport direction of the solute, secondary active transporters are classified as either symporters or antiporters. Symporters, transport the two molecules in the___ direction, whereas antiporters move their substrates in ___ directions.
•
•There are 3 types of ___ _____ (also carriers)

(1)

(2)

(3)

Answer 14

•Transport of a molecule against its gradient is energetically unfavorable, and therefore requires that the transporter harness an energy source.
•
•If energy is applied directly to the transporter (through hydrolysis of ATP), the transport is called primary active transport; if the energy is used to establish an ion gradient and the gradient is used to concentrate another compound, the transport is called secondary active transport.
•
•Depending on the transport direction of the solute, secondary active transporters are classified as either symporters or antiporters. Symporters, transport the two molecules in the same direction, whereas antiporters move their substrates in opposite directions.
•
•There are 3 types of active transporters (also carriers)

(1) ATP-driven ion pumps (primary) Ex) Na/K pump
(2) Coupled transporters (secondary) Ex) Na/Glucose Transporter
(3) ABC transporters (primary)

Question 15

Comparison between carrier-mediated facilitative diffusion and active transport

Answer 15

Same: saturation kinetics, specificity, can be inhibited

FD: move down conc grad, no E

AT: moves against conc grad, yes E

Question 16

ATPases/ ATP Pumps
•ATP-driven ion pumps utilize the energy liberated by ___ ___ to move ions across membranes, against their gradients. These proteins ____ ion gradients across both the plasma membrane and intracellular membranes.
•
•Maintenance of ionic gradients is crucial for the ___ of the cell
•

•Examples of ATP pumps

(1)
●
(2)
●
(3)

Answer 16

•ATP-driven ion pumps utilize the energy liberated by ATP hydrolysis to move ions across membranes, against their gradients. These proteins maintain ion gradients across both the plasma membrane and intracellular membranes.
•
•Maintenance of ionic gradients is crucial for the viability of a cell.
•

•Examples of ATP pumps(1)Na+/K+-ATPase
●
(2)Ca2+-ATPase
●
(3)ABC transporters

Question 17

Na+/K+ ATPase

•Na+/K+ ATPase maintains high _____ Na+ concentration and high_____ K+ concentration by transporting these ions ____ their concentration gradients.
•
•Na+/K+ ATPase ___ the membrane like a channel with binding sites for ___ Na+ ions open to the ____ side.
•

•Once Na+ ions bind, ____ _____ is used to ____ an ____ domain and change the transporter’s ____ so that bound Na+ ions are released to the ____
•
•The conformational change exposes binding sites for ___K+ ions to the ____side.
•
•Binding of K+ ions triggers the hydrolysis of the ___ ____ ____ and returns the Na+/K+ ATPase to the ____conformation and releases K+ to the ____
•
•Na+/K+ ATPase converts the ___ energy of ___ ____ into maintenance of an ____ gradient for Na+ and an ____ gradient for K+.
•
•
•
•

Answer 17

•Na+/K+ ATPase maintains high extracellular Na+ concentration and high intracellular K+ concentration by transporting these ions against their concentration gradients.
•
•Na+/K+ ATPase spans the membrane like a channel with binding sites for three Na+ ions open to the intracellular side.
•

•Once Na+ ions bind, ATP hydrolysis is used to phosphorylate an internal domain and change the transporter’s conformation so that bound Na+ ions are released to the outside.
•
•The conformational change exposes binding sites for 2 K+ ions to the extracellular side.
•
•Binding of K+ ions triggers the hydrolysis of the bound phosphate group and returns the Na+/K+ ATPase to the original conformation and releases K+ to the inside.
•
•Na+/K+ ATPase converts the chemical energy of ATP hydrolysis into maintenance of an inward gradient for Na+ and an outward gradient for K+.
•
•
•
•

Question 18

Na+/K+ -ATPase is required to maintain osmotic balance and stabilize cell volume

•Cells contain high concentration of solutes, including numerous ____ charged ___ molecules that are confined___ the cell and their accompanying ____ that are required for charge balance.
•
•This creates a ____ osmotic gradient that tends to pull water ___the cell.
•
•This effect is _____ by an opposite osmotic gradient due to high concentration of ____ ions in the ____fluid, which is primarily maintained by the _______.
•
•Since Na+/K+ ATPase drives ____positively charged ions out of the cell for every ___ it pumps in, it is ______ ie., it drives a net ____ across the membrane, tending to create an ___ ____, with the inside ____ relative to the outside – contributes to __% of the membrane potential.

Answer 18

•Cells contain high concentration of solutes, including numerous negatively charged organic molecules that are confined inside the cell and their accompanying cations that are required for charge balance.
•
•This creates a large osmotic gradient that tends to pull water into the cell.
•
•This effect is counteracted by an opposite osmotic gradient due to high concentration of inorganic ions in the extracellular fluid, which is primarily maintained by the Na+/K+ pump.
•
•Since Na+/K+ ATPase drives three positively charged ions out of the cell for every two it pumps in, it is electrogenic; ie., it drives a net current across the membrane, tending to create an electrical potential, with the inside negative relative to the outside – contributes to 10% of the membrane potential.
•
•
•
•
•

Question 19

FAQ: Why is Na+/K+ pump pumping Na+ out and K+ in if the concentration of Na+ is already high outside and K+ is high inside?

It is because of the Na+/K+ pump that the Na+ is high outside and K+ is high inside – so this pump constantly works to maintain those gradients!

Question 20

Na+/K+ ATPase drives various secondary active transport mechanisms

• In many situations, the active transport of Na+ is coupled to the transport of other substances (secondary active transport).
• A few examples are

(1) The ____ membranes of ____ cells in the ___ ____contain a ____ that transports glucose ___ the cell only if Na+ binds to the protein and is transported into the cell at the same time.
(2) In the ___ an ____ in the membranes of ___ ____ cells normally exchanges____ ___ for ___ ___.

•

Answer 20

• In many situations, the active transport of Na+ is coupled to the transport of other substances (secondary active transport).
• A few examples are

(1) The luminal membranes of mucosal cells in the small intestine contain a symporter that transports glucose into the cell only if Na+ binds to the protein and is transported into the cell at the same time.
(2) In the heart an antiporter in the membranes of cardiac muscle cells normally exchanges intracellular Ca2+ for extracellular Na+.

•

Question 21

Glucose transport in intestinal epithelial cells

In intestinal epithelial cells, intracellular glucose concentration is ____ than extracellular concentration

Yet, glucose needs to be ____ from the ___ ____ – against glucose concentration gradient

Therefore the Na-Glucose symporter uses the energy in the Na+ gradient to drive the transport of glucose ___ the cell – since energy is used, it is___transport

However, the Na+ gradient was originally created by the Na+/K+ pump using ATP – therefore, it is ___ ___ ____

When glucose is transported from the intestinal epithelial cell to ___, the transport occurs ___ the concentration gradient and therefore ___ energy is used – ___ ___

Answer 21

In intestinal epithelial cells, intracellular glucose concentration is higher than extracellular concentration

Yet, glucose needs to be absorbed from the intestinal lumen – against glucose concentration gradient

Therefore the Na-Glucose symporter uses the energy in the Na+ gradient to drive the transport of glucose into the cell – since energy is used, it is active transport

However, the Na+ gradient was originally created by the Na+/K+ pump using ATP – therefore, it is secondary active transport

When glucose is transported from the intestinal epithelial cell to blood, the transport occurs down the concentration gradient and therefore no energy is used – facilitated diffusion

Question 22

Sarcoplasmic Reticulum Ca2+ ATPase

• Plays an important role in maintaining ___ cytoplasmic Ca2+ concentration by pumping Ca2+ ____the sarcoplasmic reticulum.
• This pump maintains a Ca2+ concentration of approximately ____ in the cytosol compared with ____ in the sarcoplasmic reticulum.
• Consists of a ___ domain consisting of ___ ___ ____ and a large ____ head piece with __ domains; domain _ binds ___, ___ accepts the ____ group and _ may serve as an___ for the _ domain.

The mechanism involves:

1. The reaction cycle begins with the binding of ___ and ___ ____+ ions.
2. The enzyme cleaves ATP, transferring the ____ group to domain ___. Calcium must be bound to the enzyme for the ____ to take place. Phosphorylation causes ____ change.
3. Change in conformation causes the ion-binding sites to “___” so that the ions can ___ only to the ___ side of the membrane.
4. In this conformation, the enzyme has ___ affinity for the Ca2+ ions, so they are ____
5. With the release of Ca2+, the ______ residue is_____, and the phosphate group is ____ – the protein everts back to its___conformation.

Answer 22

• Plays an important role in maintaining low cytoplasmic Ca2+ concentration by pumping Ca2+ into the sarcoplasmic reticulum.
• This pump maintains a Ca2+ concentration of approximately 0.1 μM in the cytosol compared with 1.5 mM in the sarcoplasmic reticulum.
• Consists of a transmembrane domain consisting of 10 α helices and a large cytoplasmic head piece with 3 domains; domain N binds ATP, P accepts the phosphoryl group and A may serve as an actuator for the N domain.

The mechanism involves:

1. The reaction cycle begins with the binding of ATP and two Ca2+ ions.
2. The enzyme cleaves ATP, transferring the phosphoryl group to domain P. Calcium must be bound to the enzyme for the phosphorylation to take place. Phosphorylation causes conformational change.
3. Change in conformation causes the ion-binding sites to “evert” so that the ions can dissociate only to the luminal side of the membrane.
4. In this conformation, the enzyme has low affinity for the Ca2+ ions, so they are released.
5. With the release of Ca2+, the phosphoaspartate residue is hydrolyzed, and the phosphate group is released – the protein everts back to its original conformation.

Question 23

ATP-Binding Cassette (ABC) Transporters

•ABC transporters comprise a ___ ____of transmembrane proteins.
•
•Found in ___ and ____. Most mammalian ABC transporters are ____.
•
•They function in the transport of a wide variety of substrates, including ___, ___, ___ ___, ___and ___ ___ against their concentration gradients. One member is an ATP-gated ____ channel (Cystic fibrosis ____ ____ _____ or CFTR).
•
•Despite their great functional diversity, they all share the ___ ___ architecture. Every ABC transporter has ___ ____ domains (TMDs) coupled to ___ ____-____ domains (NBDs, also known as ATP-Binding Cassettes ABCs).
•
•Transport starts with entry of the substrate into the binding pocket on the ____side, followed by protein ____changes (driven by ___ ___ or ____), and release of substrate into the ____ space.

Note – Your text book classifies CFTR as a facilitated channel transporter. However, since it uses ATP, it should be classified as an active transporter.

Answer 23

•ABC transporters comprise a large family of transmembrane proteins.
•
•Found in prokaryotes and eukaryotes. Most mammalian ABC transporters are exporters.
•
•They function in the transport of a wide variety of substrates, including phospholipids, sterols, bile acids, peptides and metabolic drugs against their concentration gradients. One member is an ATP-gated chloride channel (Cystic fibrosis transmembrane conductance regulator or CFTR).
•
•Despite their great functional diversity, they all share the same domain architecture. Every ABC transporter has two transmembrane domains (TMDs) coupled to two nucleotide-binding domains (NBDs, also known as ATP-Binding Cassettes ABCs).
•
•Transport starts with entry of the substrate into the binding pocket on the cytoplasmic side, followed by protein conformational changes (driven by ATP binding or hydrolysis), and release of substrate into the extracellular space.

Note – Your text book classifies CFTR as a facilitated channel transporter. However, since it uses ATP, it should be classified as an active transporter.

Question 24

Receptor-mediated endocytosis

Major steps during and after endocytosis are

(1)Ligands bind to specific ____ receptors, which then associate with specific ___ ____, including ___ and ___proteins, and ____ in membrane regions to form ___ ___.
(2)Clathrin facilitates ____ of the pits, and another peripheral membrane protein, ____, forms __ ___ around the developing neck of the pit, which cause the region to ___ ___ as a ___ ___.
(3)The internalized vesicles ___ their clathrin coats and usually merge by membrane fusion with other ____ vesicles. Ligands may have different fates within the endosomal compartment:
I.Receptors and ligands may be carried to __ ___and then to ___ for ___.
II.Ligands may be ___ ____ and the receptors ____ to the cell surface.
III.Vesicles may move to and ___ with another cell surface, where the ligands are ____ again ____the cell (_____).

Answer 24

Major steps during and after endocytosis are

(1)Ligands bind to specific surface receptors, which then associate with specific cytoplasmic proteins, including clathrin and adaptor proteins, and aggregate in membrane regions to form coated pits.
(2)Clathrin facilitates invagination of the pits, and another peripheral membrane protein, dynamin, forms constricting loops around the developing neck of the pit, which cause the region to pinch off as a coated vesicle.
(3)The internalized vesicles lose their clathrin coats and usually merge by membrane fusion with other endosomal vesicles. Ligands may have different fates within the endosomal compartment:
I.Receptors and ligands may be carried to late endosomes and then to lysosomes for degradation.
II.Ligands may be released internally and the receptors recycled to the cell surface.
III.Vesicles may move to and fuse with another cell surface, where the ligands are released again outside the cell (transcytosis).

Question 25

Glucose can be transported into cells against their conc gradient because of

Answer 25

E. Symport with Na

Question 26

Which of the following statements is INCORRECT about active transport

Answer 26

A.Shows saturation kinetics
B.Requires coupled input of E
C.Cannot be inhibited
D.Shows specificity for the solute to be transported