Membrane Structure

Question 1

Lipid bilayers are dynamic and fluid structures; membrane fluidity depends on composition and temperature. Describe the movements of a typical lipid molecule.

Answer 1

exchanges places with its neighbors in a bilayer 10^7 times/second and diffuses several mm/second at 37°C within a lipid bilayer leaflet.

Question 2

Phospholipids ____ (do/do not) spontaneously flip-flop in membranes.

Answer 2

do not. For specific functions, an ATP driven Flippase catalyzes flip-flop.

Question 3

There are three classes of lipids in a membrane and all 3 classes are_____ . All are synthesized in the _____.

Answer 3

amphipathic; endoplasmic reticulum (ER)

Question 4

The three classes are:

Answer 4

phospholipids, sphingolipids, and cholesterol.

Question 5

The most common phospholipids are (4):

Answer 5

1. phosphatidylinositol (PI).
2. phosphatidylcholine (PC)
3. phosphatidylethanolamine (PE)
4. phosphatidylserine (PS)
   (ICES)

Question 6

All the lipid molecules shown are derived from ___ except for sphingomyelin, which is derived from sphingosine.

Answer 6

glycerol

Question 7

Cholesterol has a polar hydroxyl group, a rigid steroid ring group, and a hydrocarbon tail. Cholesterol is intercalated among membrane phospholipids. The interaction of the _____ tends to immobilize the lipid and____ fluidity.

Answer 7

steroid ring with the hydrophobic tail of other phospholipids; decrease

Question 8

How does the mole percentage of cholesterol change from the ER/Golgi/PM?

Answer 8

Roughly doubles. ER (7%) to the Golgi (13%) and again from the Golgi to the plasma membrane (26%).

ER<PM

Question 9

Which phospholipids inhabit the internal surface of the PM? The outside? Where does cholesterol go?

Answer 9

Negatively charged are abundant on the internal surface

iNies (inside Negative PI, PE, PS)
phosphatidylserine (PS)
phosphatidylinositol (PI)
phosphatidylethanolamine (PE)

More abundant on the external surface:

GPS
glycolipids
phosphatidylcholine (PC)
sphingomyelin

Cholesterol is thought to be distributed equally in the two leaflets/monolayers.

Question 10

We get cholesterol from? Cholesterol synthesis is regulated by a _____ mechanism.

Answer 10

(1) ingestion and uptake
(2) synthesis by the liver

Negative feedback

Question 11

The first and rate-limiting enzyme in the cholesterol production pathway is HMGCoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase). _______ block this step.

Answer 11

statins

Question 12

The bHLH transcription factor is bound to ______, which is a transmembrane protein. Under ____ cholesterol conditions, SREBP relocates to the Golgi via _____, where the bHLH is cleaved and relocates to the nucleus where it ______ transcription of all 30 cholesterol synthesis proteins.

Answer 12

SREBP; low; vesicular transport; activates

Question 13

The ____ protein binds SREBP under ____ cholesterol conditions, allowing SREBP to relocate to the golgi and be cleaved.

Answer 13

SCAP (SREBP Cleavage Activating Protein); low

Question 14

Under ____ cholesterol conditions, ____ is bound by ______, which inactivates it, preventing relocation of the _____ complex to the Golgi.

Answer 14

High; SCAP; Insig; SCAP/SREBP

Question 15

How does the SREBP/bHLH cleavage tie in to Alzheimer’s disease?

Answer 15

One cleavage that releases bHLH cuts SREBP in the transmembrane domain. This cleavage within the membrane is now known as RIP, regulated intramembrane proteolysis. RIP has been shown to be critical also for Notch signaling in development and for cleavage of the amyloid precursor protein (APP) to produce the beta amyloid peptide in Alzheimer’s disease.

Question 16

What proteases in the Golgi are responsible for cleavage of bHLH from SREBP? Are both required, or only one?

Answer 16

S1P is luminal, S2P is within the membrane – cleavage by both is required for activation