FOM 1.4.2 Flashcards
Membrane is permeable to…
○ Gases: O2, CO2 ○ Small uncharged: EtOH somewhat permeable to water
Membrane is NOT permeable to..
○ Ions: H+, Na+, K+, Cl- ○ Large, uncharged: glucose ○ Large, charged: amino acids, peptides, nucleotides, phosphate ions
describe the effects of osmotic pressure and water transport
○ Hypertonic: Lots of solute outside —> water LEAVES the cell ○ Hypotonic: Little solute outside —> water ENTERS the cell
Passive Transport
moves molecules WITH the gradient
Active Transport
moves molecules AGAINST gradient (requires energy)
Primary Transport
use energy from ATP to move molecules AGAINST the gradient
Secondary Transport
moves one molecule WITH gradient, and the energy from that moves another molecule AGAINST the gradient (can be symport or antiport)
Pores
open on both sides, very large, not common in euks, mostly beta sheets ie aquaporin in bacteria
Channels
open on both sides, opening can be regulation, can be selective for size (ie ions)
Pumps
“airlock” only one side opens at a time, requires conformational change, uses energy from ATP
Transporters
“airlock” only one side opens at a time, requires conformational change, uses energy from ATP OR driven by gradient
physiological circulating range of glucose
3.6-6.6 mM
GLUT 1
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
GLUT 2
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
GLUT 3
Km (1.4) is lower than normal range, thus when glucose levels are low, brain has priority in binding and receiving glucose
GLUT 4
Close to end-range of normal range (6.6), when glucose is higher than normal, insulin can be released and glucose will be stored
Describe the relationship between changes in ligand transport and osmotic pressure, using SGLT as an example.
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
Selectivity channel
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
Voltage sensor
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
P-type ATPase
○ Has a phosphorylated intermediate state ○ Ion transport including H+
F-type/V-type ATPase
○ H+ transport ○ In lysosome and mitochondria
ABC Superfamily
○ Drugs, lipids, ions, peptides ○ Plasma membrane and ER
Describe the structure of a typical ATP-binding cassette (ABC) transporter.
○ 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
Describe the functional cycle of a typical ATP-binding cassette (ABC) transporter.
- 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
Digoxin
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
MDR transporter
“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
What is the cell permeable, slightly permeable, not permeable to?
How is a channel different from a pore?
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
What are the characteristics of a pump/transporter?
Only one end open at a time. Associate with a conformational change. Outside energy is required.
What is a reason for GLUT2 to have a Km of 17?
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.
Why would the GLUT3 transporter require a low Km of 1.7?
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.
What is an SGLT? And why would it be important for SGLT1 in the kidney to have a Km of 0.2?
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.
Answer this question and describe the relationship between changes in ligand transport and osmotic pressure, using SGLT as an example.
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
What is the overall charge of a cell? What would this affect if a large pore was inserted into a cell?
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.
How can channels select for ions that pass through them?
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.
How does Km relate to the binding of a transporter to a ligand?
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.
Step Question
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
