FOM 1.4.2

Question 1

Membrane is permeable to…

Answer 1

○ Gases: O2, CO2 ○ Small uncharged: EtOH somewhat permeable to water

Question 2

Membrane is NOT permeable to..

Answer 2

○ Ions: H+, Na+, K+, Cl- ○ Large, uncharged: glucose ○ Large, charged: amino acids, peptides, nucleotides, phosphate ions

Question 3

describe the effects of osmotic pressure and water transport

Answer 3

○ Hypertonic: Lots of solute outside —> water LEAVES the cell ○ Hypotonic: Little solute outside —> water ENTERS the cell

Question 4

Passive Transport

Answer 4

moves molecules WITH the gradient

Question 5

Active Transport

Answer 5

moves molecules AGAINST gradient (requires energy)

Question 6

Primary Transport

Answer 6

use energy from ATP to move molecules AGAINST the gradient

Question 7

Secondary Transport

Answer 7

moves one molecule WITH gradient, and the energy from that moves another molecule AGAINST the gradient (can be symport or antiport)

Question 8

Pores

Answer 8

open on both sides, very large, not common in euks, mostly beta sheets ie aquaporin in bacteria

Question 9

Channels

Answer 9

open on both sides, opening can be regulation, can be selective for size (ie ions)

Question 10

Pumps

Answer 10

“airlock” only one side opens at a time, requires conformational change, uses energy from ATP

Question 11

Transporters

Answer 11

“airlock” only one side opens at a time, requires conformational change, uses energy from ATP OR driven by gradient

Question 12

physiological circulating range of glucose

Answer 12

3.6-6.6 mM

Question 13

GLUT 1

Answer 13

Km (3-7) is around circulating range, thus GLUT one is able to take up glucose and transport it to tissues at a normal range

Question 14

GLUT 2

Answer 14

Km (17) is much higher than circulating range, can function at high concentrations of glucose without getting saturated and quickly bind and transport it from gut cells to blood. Expressed in the islet cells and other tissues

Question 15

GLUT 3

Answer 15

Km (1.4) is lower than normal range, thus when glucose levels are low, brain has priority in binding and receiving glucose

Question 16

GLUT 4

Answer 16

Close to end-range of normal range (6.6), when glucose is higher than normal, insulin can be released and glucose will be stored

Question 17

Describe the relationship between changes in ligand transport and osmotic pressure, using SGLT as an example.

Answer 17

If more ligand is transported outside of the cell, H2O is sure to follow to maintain equilibrium With SGLT (sodium-dependent glucose transporter), if glucose transport into the cell is disrupted and glucose stays in the lumen, then water moves out of the cell into lumen –> physiologically, this leads to thirst and diarrhea

Question 18

Selectivity channel

Answer 18

backbone of proteins in the ion channel, ion-specific by size, ie Na+ ion too small to make proper interactions to pass through a K+ channel

Question 19

Voltage sensor

Answer 19

for K+ channel: protein gate with lots of (+) charged histidines (partially embedded in membrane, so very sensitive), if one side of the membrane has a build up of (+) charge from K+ ions, it repels the voltage sensor and the channel opens until the a less positive charge is re-established and the gate closes

Question 20

P-type ATPase

Answer 20

○ Has a phosphorylated intermediate state ○ Ion transport including H+

Question 21

F-type/V-type ATPase

Answer 21

○ H+ transport ○ In lysosome and mitochondria

Question 22

ABC Superfamily

Answer 22

○ Drugs, lipids, ions, peptides ○ Plasma membrane and ER

Question 23

Describe the structure of a typical ATP-binding cassette (ABC) transporter.

Answer 23

○ 1, 2, or 4 polypeptide subunits ○ Has 2 TM domains (exoplasmic): § Specific for different ligands § 7 subclasses § Not conserved ○ Has 2 nucleotide binding domains (cytosolic) § For binding ATP

Question 24

Describe the functional cycle of a typical ATP-binding cassette (ABC) transporter.

Answer 24

1. Ligand binds OPEN conformation on cytosolic side 2. ATP binds —> CLOSED conformation —> Ligand released on exoplasmic side 3. ATP hydrolyzed 4. ADP and Pi released —> back to OPEN conformation

Question 25

Digoxin

Answer 25

cardiac glycoside that is able to inhibit the Na+/K+ ATPase, blocks transport of K+ into the cell –> INCREASE in Na+ –> INCREASE in Ca2+ and slower, longer heart contractions

Question 26

MDR transporter

Answer 26

“Multi-Drug Resistant” (aka P-glycoprotein) transporter is a specific ATP binding cassette transporter that is resposible for a lot of drug resistance in tumor cells and pathogens, pumps drugs out of cells before they can have any effect

Question 27

What is the cell permeable, slightly permeable, not permeable to?

Answer 27

Question 28

How is a channel different from a pore?

Answer 28

Channel is open on both ends only during the passage. Opening and closing is regulated.

A pore has both ends open at all times and allows for the free flow of large particles

Question 29

What are the characteristics of a pump/transporter?

Answer 29

Only one end open at a time. Associate with a conformational change. Outside energy is required.

Question 30

What is a reason for GLUT2 to have a Km of 17?

Answer 30

This is associated with a weaker affinity for binding glucose. Because of this, during times of fasting it prevents much of the glucose from being moved back into the blood.

Question 31

Why would the GLUT3 transporter require a low Km of 1.7?

Answer 31

The low Km associated with GLUT3 means that it has a strong binding affinity for glucose. The brain uses glucose, and in periods of fasting the brain needs to take priority glucose utilization. This means it will grab most of the glucose in surrounding areas.

Question 32

What is an SGLT? And why would it be important for SGLT1 in the kidney to have a Km of 0.2?

Answer 32

SGLT is an example of a secondary active transport. It relies on the Na+ gradient to drive the glucose uptake against the glucose gradient. SGLT1 is located in the kidney, which is a site for glucose reabsorption in the body. This enzyme needs to grabs all the glucose possible in order to filter it out of the urine.

Question 33

Answer this question and describe the relationship between changes in ligand transport and osmotic pressure, using SGLT as an example.

Answer 33

C

If more ligand is transported outside of the cell, H2O will follow to maintain equilibrium

With SGLT(sodium-dependent glucose transporter), if glucose transport into the cell is disrupted and glucose stays in the lumen, then water moves out of the cell into the lumen - leads to thirst and diarrhea

Question 34

What is the overall charge of a cell? What would this affect if a large pore was inserted into a cell?

Answer 34

The cell has an overall negative charge associated with it. If a large pore were inserted into it, the positively charge sodium that is in higher concentrations on the outside of the cell would begin to enter the cell unregulated. This would cause H2O to follow and thus swell the existing cell.

Question 35

How can channels select for ions that pass through them?

Answer 35

Channels contain amino acids that are able to sense the incoming ion. In a potassium channel, the size of the potassium ion allows for it to pass more freely, while sodium is too small.

Question 36

How does Km relate to the binding of a transporter to a ligand?

Answer 36

If the Km is lower than the ligand concentration it will pick up ligand and if the Km is lower than ligand concentration it will drop it off.

Question 37

Step Question

Answer 37

E - This is a connexion protein of gap junction. This means that cell to cell communication is occurring, thus meaning the mutation most like occurs in the transmembrane region