Cell Membrane

Question 1

Phosphoglycerides

Answer 1

1. Two fatty acid chains attached to two of the three carbons of glycerol backbone
   
   1. One chain has kink: opposes dense packing and increases fluidity—otherwise membrane would solidify and freeze at physiologic temperature
2. Remaining third glycerol attached to phosphate which can be attached to three major head groups
   
   1. Choline: positively charged but net charge of phosphotidylcholine is 0.
   2. Ethanolamine: positively charged but net charge of phosphotidylethanolamine is 0.
   3. Serine: net charge is 0 but phosphate has - charge so overall net charge of phosphotidylserine is -1.

Question 2

Shingomyelin

Answer 2

1. Two fatty acid chains attached to two of the three carbons of glycerol backbone
   
   1. One chain has kink: opposes dense packing and increases fluidity—otherwise membrane would solidify and freeze at physiologic temperature
2. Hydroxyl group attached to a phosphate which is attached to a choline head group.
   
   1. Net charge is 0.

Question 3

Cholesterol

Answer 3

1. Structure
   
   1. Polar molecule
   2. Terminal OH near membrane surfaces in both leaflets
   3. Small molecule
2. Function
   
   1. Small molecule so it can sit in either inner or outer leaflet of the lipid bilayer
   2. Polar group extends outside to interact with aqueous environment
   3. Aliphatic chain of cholesterol interacts with aliphatic chain of phospholipids in the lipid bilayer and keep these phospholipid chains apart to keep fluidity in the membrane structure.

Question 4

Glycolipids

Answer 4

1. Derived from sphingosine with sugars added to hydroxyl instead of the phosphate.
2. Asymmetric in that sugar is only added to external face of plasma membrane
   
   1. GM1 ganglioside is used for entry of cholera toxin

Question 5

Lipid composition of intracellular membranes vs. plasma membrane

Answer 5

1. Plasma membrane
   
   1. Cholesterol
   2. Spingomyelin
   3. Glycolipids- derives from sphingosine backbone with sugars attached to OH
2. Inner organelle membranes
   
   1. Phosphotidylethanolamine
   2. Phosphotidylcholine

Question 6

Asymmetry between inner/outer leaflets

Answer 6

1. Inner leaflet
   
   1. Phosphotidylehtanolamine
   2. Phosphotidylserine
2. Outer leaflet
   
   1. Glycolipids
   2. Shphingomyelin
   3. Phosphotidyl choline

Note: cholesterol is distributed equally between leaflets

Question 7

How are lipid rafts formed in inner and outer membrane leaflets?

Answer 7

1. Spingomyelin, which has a slightly longer fatty acid tail, compared to phosphoglycerides, and in some cases, it can associate with cholesterol which creates a subdomain of outerleaflet that is thicker than remaining membrane
2. The life rafts can then recruit subset of membrane proteins in order to convey some coordinated cellular or metabolic response.

Question 8

Two PI derived signaling pathways

Answer 8

1. Phosphorylation
   
   1. Ligand binds to receptor protein
   2. Receptor protein is phosphorylated
   3. PI3 kinase docks on to phosphorylated receptor protein and becomes phosphoryalted
   4. PIP3 kinase then phosphorylates PIP3 which serves as dock for downstream signaling molecules
2. Cleavage
   
   1. Ligand binds to receptor protein
   2. Receptor protein activates phospholipase C
   3. Phospholipase C cleaves PIP3 into IP3
   4. IP3 can then be released from cell membrane and relay signal

Question 9

Spectrin

Answer 9

Cytoskeletal protein spectrin is a dimer attached indirectly (via intermediates) to the transmembrane proteins glycophorin and/or band 3

Question 10

Channel

Answer 10

1. Channels open and close
2. They allow for the passage of molecules that are asymmetrically distributed in terms of concentration
3. When channels open, due to the difference in concentration from the inside to the outside of the cell, the ions move.
4. Channels can transport ions rapidly.
5. The channels, however, are not very selective. The specificity for any ion is not as great as it is for other mechanisms of transport.

Summary

1. Not very selective
2. Rapid
3. Down a concentration gradient
4. You don’t need energy

Question 11

Carrier

Answer 11

1. Intermediate in specificity for molecules it will be transporting
2. Does not transport molecules as fast as a channel
3. It transports molecules downhill
4. You can pull a molecule uphill against a concentration gradient by coupling it with the downhill transport of a molecule along its concentration gradient.
5. Does not require energy

Question 12

Pump

Answer 12

1. It has high specificity for the molecules it will be transporting
2. It transports material slowly
3. Instead of transporting material down a concentration gradient, you can transport molecule against its concentration gradient.
4. You need a source of energy which comes from ATP

Question 13

Ion Channels

Answer 13

1. K+, Na+, Ca2+
2. Channels reject inappropriate ions based on size and charge
3. Channels can be found in 3 conformations
   
   1. Open: allow ions to pass through
   2. Closed: do not allow ions to pass through
   3. Inactivated: channel is open but ions cannot pass through due to blockage by an accessory or ball

Question 14

Sodium channel blockers

Answer 14

1. Tetrodotoxin
   
   1. Paralyze skeletal muscle by blocking Na+
2. Lidocaine
   
   1. Anesthetic

Question 15

Potassium channel blockers

Answer 15

Scorpion or snail toxins

Question 16

Nicotinic acetylcholine receptor blocker

Answer 16

1. Na/K channel
   
   1. Normally binds Ach
2. Curare is antagonist of Ach

Question 17

Symporter

Answer 17

1. A molecule can bind to symporter on one side and be moved to the other side down its concentration gradient
   
   1. The free energy released from moving this molecule down its concentration gradient can be used to drive the second transport step
2. Another molecule from the same side of the membrane that the first molecule bound to can be moved against its concentration gradient to the other side

Question 18

Transport of Glucose from intestine into epithelia

Answer 18

Used for glucose getting from intestine into epithelial cells

1. Concentration
   
   1. Glucose higher inside cell
   2. Na+ higher outside cell
   3. Helps transport leftover glucose from outside cell (interstine) into the epithelium
2. Apical part of epithelial cell has Na/glucose symporter
   
   1. Symporter is open to the outside
   2. Na+ binds to carrier symporter
   3. This increases binding affinity for glucose
   4. Both of the sites are occupied activating a conformational switch
   5. Symporter becomes open to the inside
   6. Na+ and glucose are released to the inside
3. Basolateral part of epithelial cell has a glucose uniporter and Na/K pump
   
   1. Glucose unporter
      
      1. Since concentration of glucose is high inside epithelial cell, glucose goes down its concentration gradient being transported from inside epithelial cell to out in the blood stream
   2. Na/K pump
      
      1. Needed to maintain the intracellular Na+ concentration low so that the Na+ is continued to be transported inside cell along with glucose in the apical membrane.
      2. It pumps 3Na+ out of cell and 2K+ inside cell.

Question 19

ATP pump types

Answer 19

1. P-type
   
   1. Multipass transmembrane domains
   2. Autophosphorylate themselves with P from ATP
   3. Phosphorylation induces a conformational change that pumps ions
2. F-type
3. ABC transporter
   
   1. Transport small molecules
   2. Involved in multidrug resistance

Question 20

P-type Ca2+ pump

Answer 20

1. Cytoplasmic Ca2+ concentration needs to be maintained at a low level so Ca2+ is sequestered into sarcoplasmic recticulum where Ca2+ is stored at high concentration. Since Ca2+ is being transported from area of low concentration to area of high concentration, P-type pump is needed.
2. Process
   
   1. Ca2+ in cytoplasm binds P-type pump in non-phosphorylated manner
   2. Arginine residue is phosphoryalted by ATP
   3. Conformational change occurs
   4. Ca2+ is released from binding site and enters storage into Sarcoplasmic Recticulum.

Question 21

P-type Na/K pump

Answer 21

1. Na+ concentration is high inside cell and K+ is high outside cell after action potential
2. Process
   
   1. 3 Na+ bind inside cell
   2. Phosphorylation of pump causes conformational change
   3. Na+ released to outside of cell
   4. 2K+ bound outside of cell
   5. Dephosphorylation leads to conformational change
   6. K+ enters into cell

Question 22

ABC pump

Answer 22

1. Transport small molecules against concentration gradient
   
   1. Used in bacteria for import
2. Process
   
   1. Small molecule binds in unphosphorylated state
   2. ATP bind to ATPase domains
   3. When 2 ATP are bound, the ATPase domains dimerize
   4. Dimerization causes conformational change that exposes substrate to opposite side of membrane
   5. ATP hydrolysis releases substrate
3. In multiple drug resistance (MDR), high levels of one type o ABC transporter can arise in tumor cells, which allows more hydrophobic drug to be cleared from cytoplasm so that drug effects are reduced (occurs in 40% cancer patients)