Lipid Membrane and Solute Transport Flashcards
What are lipid bilayers used for? (2)
- Membrane organelles
- Cytoplasmic membrane
What provides the unique features of the different plasma membranes in various organisms?
The plasma membrane can differ based on the organism, the cell type, and the organelles involved
How are the levels of cholesterol in the plasma membrane? What about the rough ER?
Plasma membrane: high cholesterol
Rough ER: low cholesterol
What do we mean by “asymmetry” of the lipid bilayers?
- The distribution of membrane phospholipids can either be more present in the inner or outer monolayer
- The difference is very important
Where is phosphotidylinositol located in the cell membrane?
Inside of the membrane since they are involved in signal transduction
Where is phosphotidylserine located in the cell membrane?
Located on the inside of the membrane, but sometimes is shifted to the ouside
How can integral membrane proteins be separated?
- Using detergents
- Makes the hydrophobic portion of IMP soluble
What do peripheral membrane proteins interact with?
- Linked to the lipid bilayer
- Linked with transmembrane proteins
- Linked through a carbohydrate (ex: Glycosylphosphatidylinositol)
Differentiate the ordered and disordered states of the lipid bilayer.
Ordered state; membrane is crystalline; gel-like
Disordered state: membrane is very fluid
Are cell membranes usually ordered or disordered?
- Neither, cells are always in between these two states
- Different cells will have different ideal fluidity ranges
How does heat affect the cell membrane?
- Produces thermal motion of the side chains
- Gel to fluid transition
How does temperature affect membrane flexibility?
If the temperature increases over 40oC, the lipid bilayer goes into the disordered state (increases thermal motion)
What is the regular temperature range for membranes?
20-40oC
How does saturation of the fatty acid chains affect membrane flexibility?
- They increase order
- The more fatty acids, the more likely you will be in a crystalline state
- Unsaturated fatty acids have a kind
- Saturated fatty acids pack better
How does uniform length of the fatty acid chains affect membrane flexibility?
Increases order
How does sterol content affect membrane flexibility?
- Affects both ways depending on the situation their in
- Can decrease order if the bilayer has all saturated FA since sterols induce gaps in the bilayer, which increases disorder
- Can increase order if the bilayer has all unsaturated fatty acids since sterols will fill in the gaps
At higher temperatures, will the cells increase saturated FA or unsaturated FA in the membrane?
- Increase saturated FA
- Because they have to maintain homeostasis of fluidity
- High temp: disorder
- Saturated FA: order
Differentiate lateral diffusion and transbilayer diffusion.
Lateral: within each leaflet; lipid molecules can flow freely
Transbilayer (Flip-Flop): one leaflet to another; difficult and extremely slow (if uncatalyzed)
What is uncatalyzed lateral diffusion necessary for?
In order to change the shape of the cell, to move cells, for lipid signaling
What are the three transmembrane transporters that allow transbilayer translocations?
- Flippase
- Floppase
- Scramblase
What are flippases? Does it require ATP? If not, what does it use? Does it have directionality?
- Bring a lipid form the OUTER leaflet to the INNER leaflet
- Requires ATP
- Directionality
What triggers apoptosis/phagocytosis? What can prevent this from happening? What is it necessary for?
- PE and PS on the outer leaflet will cause apoptosis and phagocytosis (necessary for clot formation)
- Flippases move PE and PS from outer leaflet to inner leaflet
- Apoptosis/Phagocytosis is prevented
What are floppases? Does it require ATP? If not, what does it use? Does it have directionality?
- Bring a lipid from the INNER leaflet to the OUTER leaflet
- Requires ATP
- Directionality
What are scramblases? Does it require ATP? If not, what does it use? Does it have directionality?
- Moves lipids in either direction, towards equilibrium
- Does not require ATP
- Uses calcium instead
- No directionality
Can proteins move freely across the leaflet in the lipid bilayer?
Yes, if they are not anchored
What are proteins often anchored to in the bilayer? What are they?
- Ankyrin and Spectrin
- Cytoskeletal filaments in the cell
What happens if proteins in the bilayer are not anchored?
They will move
What happens if the composition on the outer leaflet has increased levels of sphingolipids and cholesterol?
- Increased rigidity
- Everything in the rigid region moves together; they are called rafts since they drift together
What are caveolae?
Caveolae are a type of “raft” that form when caveola is concentrated in a region
How does a caveolae form? How does it change the plasma membrane?
- A caveolin will interact with 3 fatty acyl moieties
- Two caveolin will dimerize (6 fatty acyl moieties total)
- When they concentrate, they will form a curvature in the plasma membrane, forming a caveolae
How do caveolae affect integral proteins?
When caveolae are formed, integral proteins in the area are stuck
- Because of this, they also become a sort of raft
What are caveolae important for?
Signal localization and signal integration
What does the fusion of two membranes require?
- Triggering signal
- Membrane recognition of each other
- Close apposition
- Local disruption of the bilayer on both membranes
- Hemi-Fusion (one of the leaflets from each side fuses)
- Fusion Proteins
What is the fusion and defusion of lipid bilayers necessary for?
- Exocytosis (sent out of the cell)
- Endocytosis (taken into the cell)
- Fertilization (fusion of sperm and egg)
- Cell division (separation of two plasma membranes)
When does membrane fusion happen at the synapse?
When a neurotransmitter is transmitted into the synaptic cleft
Which proteins draw two membranes together during membrane fusion?
- v-SNARE (vesicle)
- t-SNARE (transmembrane)
- Recognize and bind to each other, zipping up and drawing the two membranes together
What does zipping up cause during membrane fusion? What does it lead to?
- Causes curvature on the cell membrane and on the vesicle
- Favouring hemifusion between outer leaflets
What is hemifusion?
Inner leaflet of both membranes come into contact
What does complete fusion create? How are the vesicle contents released outside of the cell?
- Creates a fusion pore
- Pore widens; vesicle contents are released
What is simple diffusion? What can pass through?
○ Non-polar, small, lipid soluble compounds
○ Travel down the concentration gradient (high to low)
What is facilitated diffusion?
Travel down the electrochemical gradient
What is primary active transport?
- Requires ATP
- Travels AGAINST the electrochemical gradient
What is secondary active transport?
- Requires ATP
- Travels AGAINST the electrochemical gradient
- Movement of one solute provides the energy for the moving of another solute by a neighbouring transporter (or in the same complex)
What is an ion channel?
○ Travels down the electrochemical gradient
○ May be gated by a ligand or ion
Can polar molecules traverse the lipid bilayer?
No, they have to be hydrated to pass
What is the advantage of using a transporter in simple diffusion?
- Simple diffusion requires a lot of energy
- The transporters will lower the energy since it is the transporter that interacts with the lipid bilayer
- Increases the speed
What are the two types of transporters?
- Carriers
- Channels
What are carrier transporters?
- Slow and saturable
- Physically interact with the solute they carry
- Include primary active transporters, passive transporters and secondary active transporters
What are channel transporters?
- Fast and not saturable
- Energy and concentration gradient
What is a passive transporter?
- Does not use energy
- Moves solutes down the concentration gradient (high to low)
Give an example of a passive transporter.
- Glucose Transporters
- Transporters have two conformational statuses (T1 and T2)
- T1: transporter is open to the outside; glucose binds
- T2: transporter closes to the outside and opens to the inside; glucose is released inside, will then revert back to T1
- Rate: 50 000 times faster than the uncatalyzed diffusion
How are glucose transporters regulated?
By the hormone insulin
How does insulin affect the GLUT 4 receptor?
1) Normally, GLUT4 is kept within the cell in membrane vesicles (not available to help glucose come in)
2) When the insulin receptor is activated, it will bring the vesicle to the cell membrane, GLUT4 will get exposed to the exterior and glucose will flow in
3) When the insulin concentration goes down, the glucose transporters are brought back into the cell by endocytosis, forming small vesicles (catalyzed by PKB)
What does the lack of signal transduction in insulin dependent glucose transporters lead to?
Diabetes mellitus
Where does facilitated passive transport of ions happen in the body?
- In red blood cells
- Carries oxygen from lungs to the tissues
- Carries CO2 from the tissues to the lungs
What happens to RBC at the tissue level?
- Outside the RBC: more CO2, which diffuses in
- CO2 needs to be transformed
- It becomes HCO3-
- HCO3- dissolves in the blood plasma WHILE Cl- enters in
What happens to RBC in the lungs?
- Outside the RBC: less CO2, which diffuses out
- HCO3- comes in (leading to H2O and CO2) WHILE Cl- goes out
- CO2 is excreted through respiration
What are the three types of ion passage?
- Uniport
- Symport
- Antiport
What is a uniport?
Moves one ion from one side to the other side
What is a symport?
Cotransport involves two solutes in the same direction
What is an antiport?
Cotransport in the opposite direction
What are the two stages of the P-Type ATPase?
E1-P and E2-P
What are the three domains in the P-type ATPase?
N: nucleotide binding domain
P: phosphorylated domain
A: actuator domain
Which domain allows the P-type ATPase to get phosphorylated?
The P domain
Explain the E1 conformation of the P-type ATPase.
- Opening is toward the cytoplasm
- Binding sites for 2 calcium ions
- N domain is NOT bound to ATP
What happens when calcium binds to the P-type ATPase?
ATP, and magnesium, are brought to the N domain
What happens when ATP binds in the P-type ATPase?
- Brings P and N closer
- Phosphorylation of Aspartate-351 in the P domain
What does the phosphorylation of Aspartate-351 in the P domain in the P-type ATPase lead to?
- Phosphorylation leads to conformational changes
- Releases Ca2+ to the lumen (outer)
What causes the release of ADP and magnesium in the P-type ATPase??
- A domain moves in and breaks the partnership between P and N
- Causes the release of ADP and magnesium
- P domain becomes dephosphorylated
- A domain is reset
What type of transport is the Na+/K+ pump that maintains resting membrane potential?
Cotransport (antiport) by P-Type ATPase
How does the Na+/K+ pump work?
- ATPase pump
- Not Ca2+ that binds
- Na+ (inside) binds, causes conformational change, is released to the outside
- K+ (outside) goes in through cotransport (antiport)
What maintains resting membrane potential?
Na+/K+ pump cotransport by P-type ATPase
In the F-type ATPase, which side transports ions? Which side catalyses ATP to ADP?
- Transmembrane portion: transports ions
- Cytoplasmic side: catalysis of ATP to ADP
In the F-type ATPase, what happens if a proton goes in? What happens if a proton goes out?
In: ATP to ADP is catalyzed
Out: ADP to ATP is catalyzed
Which ATPase is present in the mitochondria of Eukaryotic cells?
F-type
How are solutes transported? Give examples of solutes.
- ABC transporters
- Amino acids, peptides, proteins, metal ions, lipids, bile salts, and drugs
What does ABC transporter stand for?
ATP-binding cassette
What do ABC transporters do?
Transport ions and solutes from the extracellular space to the cytoplasm
The fluidity of the lipid bilayer will be increased by:
A) Decreasing number of unsaturated FA (opposite, no)
B) Decreasing the temperature (opposite, no)
C) Increasing sterol content (sterol does both depending on the situation, does not necessarily increase)
D) Increasing the length of the alkyl chains (uniformity of length that makes it less fluid, not precise enough to be correct)
E) Substituting 18:0 (stearic acid) by 18:2 (linoleic acid) (saturated with unsaturated FA will increase fluidity)
Substituting 18:0 (stearic acid) by 18:2 (linoleic acid) (saturated with unsaturated FA will increase fluidity)
Identify the molecules derived from cholesterol:
- Arachidonic acid - Gangliosides - Phosphatidylglycerol - Prostaglandins - Cortisol
Cortisol
What transporter class do flippases belong to?
P-Type ATPase
What transporter class do floppases belong to?
ABC transporters
What do scramblases use since they don’t utilize ATP?
Calcium
Are P-type or F-type ATPases reversible?
- P-type ATPase is not reversible
- F-type ATPase IS reversible