Lecture 7 - Membrane Structure and Transport

Question 1

General features of the Fluid Mosaic Model: thermodynamic considerations for bilayers, favorability/unfavorability of lateral vs transverse diffusion of phospholipids

Answer 1

Fluid: lipids and proteins in membrane can move laterally

Mosaic: comprised of different lipids and proteins

Thermodynamic considerations: phospholipids are amphipathic (polar head, nonpolar tails) => polar heads face water, nonpolar tails face each other

Lateral > transverse diffusion of phospholipids b/c eliminates need for amphipathic parts to flip (otherwise need an enzyme)

Question 2

Membrane function: Compartmentalization

Answer 2

Membranes form continuous sheets that enclose intracellular compartments

Question 3

Membrane function: Scaffold for biochemical activities

Answer 3

Membranes provide a framework (resulting from physical positioning of protein complexes) that organizes enzymes for effective interaction - also creates protective/”reductive” environment that protects proteins + DNA from oxidative stress

Question 4

Membrane function: Selectively permeable barrier

Answer 4

Membranes allow regulated exchange of substances b/t compartments

Question 5

Membrane function: Transporting solutes

Answer 5

Membrane proteins facilitate the movement of substances b/t compartments

Question 6

Membrane function: Responding to external signals

Answer 6

Membrane receptors transduce signals from outside the cell in response to specific ligands

Question 7

Membrane function: Intracellular interaction

Answer 7

Membranes mediate recognition and interaction b/t adjacent cells => important for formation of larger cell-based structures like tissues and organs

Question 8

Membrane function: Energy transduction

Answer 8

Membranes transduce photosynthetic energy, convert chemical energy to ATP, and store energy

Ex: mitochondria and chloroplasts are double membrane

Question 9

Membrane lipid function and examples

Answer 9

For formation of membrane; Ex: Phospholipids, specifically glycerophospholipids

Question 10

Storage lipid example

Answer 10

For energy storage; Ex: Triglycerides (dietary lipids)

Question 11

Phospholipid structure:

Answer 11

Glycerol backbone + (phosphate + head group) + fatty acid tails (saturated/unsaturated)

Head group in glycerophospholipids is alcohol

Question 12

Fatty acid structure:

Answer 12

Carboxyl group attached to hydrocarbon tail (can be saturated or unsaturated)

Question 13

Effects of temperature on membrane fluidity; compensation mechanism for unicellular organisms

Answer 13

• Less heat => ordered => lower fluidity
• More heat => disordered => more fluidity

More important for unicellular organisms than multicellular b/c latter have thermal regulation

Unicellular compensation mechanism via enzymes:
If hot -> increase saturated fatty acids, decrease unsaturated fatty acids
If cold -> decrease saturated fatty acids, increase unsaturated fatty acids

Question 14

Effects of fatty acid saturation on membrane fluidity

Answer 14

• Saturated => straight => ordered => lower fluidity
• Unsaturated -=> bent/kinks => disordered => more fluidity

Question 15

Effects of sterols (cholesterol) on membrane fluidity

Answer 15

• More cholesterol insertion => more fluidity
• Less cholesterol insertion => lower fluidity

Question 16

Triglyceride structure:

Answer 16

Glycerol backbone + 3 fatty acids

Question 17

Steroid/sterol structure:

Answer 17

Polar head + 4 carbon ring steroid nucleus + alkyl side chain

Question 18

Asymmetry of membranes

Answer 18

The differences in lipid composition on each layer of the cell membrane bilayer

Question 19

3 membrane proteins:

Answer 19

1. Peripheral proteins
2. Integral/transmembrane proteins
3. Lipid anchor proteins (GPI-linked protein)

Question 20

What are lipidation rxns of proteins?

Answer 20

• Specific AA on protein is covalently modified through attachment of various kinds of lipids
• Attached lipid can insert into bilayer => draws protein to cell membrane => protein localize to membranes via lipidation (or also GPI anchors)

Question 21

What are isoprenylation rxns of proteins?

Answer 21

• Attachment of different sized isoprenyl group

Question 22

Structural features of peripheral proteins

Answer 22

• Can be lipidated
• Can interact directly w/ phospholipid head group
• Can interact w/ other proteins (integral proteins)
• Can be covalently linked to specific lipids (GPI Anchor)

Question 23

Structural features of integral/transmembrane proteins

Answer 23

• Can be alpha helices or beta-sheets/barrels
• Alpha helices can cross bilayer either once or multiple times
  => if once, usually act as receptor, R groups must have stretches of nonpolar AA (amphipathic alpha-helix)
  => if more than once, usually act as transporter, outer alpha helices must be nonpolar and inner alpha helices must be polar for hydrophilic molecule transport (amphipathic alpha-helix)

Question 24

What is a lipid raft?

Answer 24

• Microdomains in plasma membrane that diffuse laterally
• Contain clusters of specialized proteins (ex: signal transduction), high cholesterol content, and lipidated proteins
• Structural and functional unit of various proteins important for certain things
• Idea of localized signal transduction modules

Question 25

What are hydrophobicity/hydropathy plots?

Answer 25

Predict location of transmembrane domains in proteins

Question 26

What is simple diffusion? Effect of polarity and size? Why does this effect exist?

Answer 26

Solute diffuses through bilayer down its concentration gradient depending on polarity and size Polarity and size in increasing diffusion rate (ions < large uncharged polar < small uncharged polar < nonpolar molecules) Polar/charged molecules often form hydration shell, and removal of such shell is endergonic => high Ea for diffusion

Question 27

What are the types of membrane transport proteins?

Answer 27

Transporters (conformational change after solute binds) and channels (aqueous pore)

Question 28

Movement of electrically neutral solutes vs charged solutes

Answer 28

Neutral: down concentration gradient until equilibrium reached Charged: combo of electrical and chemical potential difference Equilibrium w/o electrical potential across membrane has equal particles and charge on both sides Equilibrium w/ electrical potential across membrane has unequal number of particles and charges on each side

Question 29

What is passive transport? How do proteins deal with hydration shell?

Answer 29

AKA facilitated diffusion; transport of molecules down concentration gradient via transporters or channels w/o ATP Hydration shell: protein form noncovalent bonds w/ dehydrated solute to replace H-bonding with water or by creating a hydrophilic transmembrane passageway/pore

Question 30

What is active transport? What are the associated forms of energy?

Answer 30

Transport of molecules via transport proteins that use a form of energy Energies: ATP, light, or coupled/cotransport

Question 31

How does coupled/cotransport work?

Answer 31

Relies on electrochemical gradient established by a pump

Question 32

3 types of transporter-mediated movement

Answer 32

1. Uniport 2. Symport 3. Antiport Symport and antiport are cotransport

Question 33

3 examples of transporters

Answer 33

1. Glucose transporters 2. Na+/K+ ATPase 3. ATP synthase

Question 34

Elaborate on glucose transporter (Glut1)

Answer 34

- Glut1 uniporter - Facilitated diffusion (works w/ [glucose] gradient) or cotransport - Multi transmembrane domains - Amphipathic alpha helices

Question 35

What regulates Glut1 expression?

Answer 35

insulin hormone

Question 36

How do amphipathic alpha helices work in transporters?

Answer 36

Some residue stretches of alpha helix are polar, others nonpolar When clustered to higher order, polar residues face transported molecule and nonpolar residues face hydrophobic membrane

Question 37

Elaborate on Na+/K+ ATPase

Answer 37

- Electrogenic pump, primary active transport - 3 Na+ pumped out, 2 K+ pumped in => net negative charge inside cell - Phosphorylated during transport - Kind of like antiport, except both Na and K are pumped against gradients

Question 38

How does Na+/K+ ATPase pump drive glucose uptake into bloodstream? What are the sources of energy for glucose to be transported into bloodstream?

Answer 38

- Cell has negative charge, low sodium, and high glucose - Na+-glucose symporter in intestinal lumen is a symporter => sodium enters cell down gradient, glucose against gradient - Glucose uniporter (ex: Glut2) facilitates glucose export down gradient into blood Two sources of energy: 1. [Na+] outside >>>> [Na+] inside 2. Transmembrane potential (inside negative, draws Na+ inward => glucose inside cell >>>> glucose outside cell (Refer to slides 58 and 59 lec 7)

Question 39

Elaborate on ATP Synthase

Answer 39

- How eukaryotes make ATP in mitochondria - Last step in ETC - Fo unit is water insoluble transmembrane proton pore -F1 unit is water soluble peripheral membrane protein complex - Couples ATP synthesis (endergonic) with passive diffusion of protons through inner mitochondrial membrane (exergonic)

Question 40

Uncoupling of ETC from ATP synthesis generates ________ via pore protein ______ which allows protons to flow down gradient like the ________ of ATP synthase

Answer 40

Heat; thermogenin; Fo unit