Membrane Structure Flashcards
- Describe the molecular components of a membrane.
Lipids, carbohydrates, and proteins. Lipids form primary membrane structure, and generally have carbs attached on extracellular surface. Proteins tend to be embedded in the membrane or attached to it. 5 nm thick; dynamic and fluid and moving fast (lateral diffusion, flexion and rotation of hydrophobic tails; rarely flip-flopping). A sealed bilayer is energetically favorable because it avoids exposure of hydrophobic tails to water.
- Describe the concept of membrane fluidity.
Dynamic and fluid membrane; depends on composition and temperature. Lots of fast movement lateral diffusion, flexion and rotation of tails). Energetically favorable to have a sealed membrane (that’s why we need special proteins for membrane fusion).
Cholesterol stiffens the membrane. Curvature is dependent on size of polar head groups on both sides of membrane.
- Identify the parts of a phospholipid, sphingolipid, and cholesterol.
3 classes of lipids in a membrane and all 3 are amphipathic (with hydrophilic and –phobic domains).
1) Phospholipids (phosphatidylethanolamine, -choline, -serine, and –inositol) are derived from glycerol. Glycerol-3-phosphate backbone with 2 fatty acyl chains.
2) Sphingolipds: instead of glycerol, have a sphingosine with either of 2 polar head groups and a fatty acid chain. –Sphingomyelin = phosphocholine head group + sugars (made in ER and finished in Golgi)
3) Cholesterol = polar hydroxyl group + rigid steroid ring group + hydrocarbon tail –> intercalates among membrane phospholipids to immobilize them and decrease fluidity. Lipids are forced straight by cholesterol.
- Describe the asymmetry of membrane bilayers.
Bilayers are asymmetric in that the inner and outer ‘leaflet’ (aka layer) aren’t composed of the exact same things. PS, PE, and PI more abundant on internal surface (negatively charged), while PC, sphingomyelin, and glycolipids are more abundant on external surface. Cholesterol is equally distributed between 2 layers.
- List the different ways proteins associate with membranes.
Integral proteins = fully or partially embedded in membrane. Transmembrane domains are usually alpha-helices, but can also have beta-sheet barrel formations. Some may have covalently attached fatty acid chain.
Peripheral membrane proteins are covalently interacting with proteins bound in the membrane, but aren’t embedded themselves. May be attached to cytosolic surface by alpha helix or lipid chain or an oligosaccharide linker.
Glycosylphosphatidylinositol can act as an anchor for proteins on the extracellular side of the membrane; can be targeted by Aeromonas hydrophilia bacteria that binds to the GPI linkage, inserts into the membrane, forms a pore and kills the cell.
- Provide an explanation for the genetic basis of familial hypercholesterolemia, its relation to atherosclerosis, and the treatment for this disease.
Familial Hypercholesterolemia Example:
- 10 year old girl first heart attack at 8
- she has xanthomas, swellings or rather deposits of cholesterol
- basically the macrophages that eat up the cholesterol dont and you get the xanthomas.
- In terms of atheroscelerosis, the same buildup seen on the skin is happening within the childs coronary arteries.
- She has a knockout of the LDLR
- She cant bring in LDL, the particles buildup in the blood. her case led to the study of all the cholesterol regulation.
-As far as treatments, probs statins would be your first go to since it inhibits the rate limiting step of cholestrerol synthesis HMGCoA reductase.
- Explain how cholesterol synthesis is regulated by gene transcription, cholesterol sensing in the ER and transcription factor release in the Golgi. How is the control of this pathway regulated by statins?
-Cholesterol synthesis depends on approximately 30 enzymes.
-The first one is HMGCoA reductase (which can be inhibited by statins).
-Uptake/synthesis regulated by sterol regulatory element binding protein (SREBP), which contains a TF (this TF is a bHLH) that regulates LDLR and the 30 synthesis proteins. Think of it as the “master regulator.”
If low cholesterol, TF (bHLH) is released –> goes to nucleus and activates transcription of all 30 of those these genes in addition to the LDLR thus making cholesterol. -Cholesterol sensor is in ER membrane.
-TF, like we said is a bHLH DNA-binding protein that is activated when cleaved from SREBP.
- The actual cleavage proteases are located in Golgi.
-SCAP binds SREBP and Insig binds SCAP (when cholesterol is high to block the signaling domain of SCAP).
-Insig prevents movement of SREBP/SCAP complex to Golgi during periods of high cholesterol.
-In low cholesterol, SREBP needs to go to Golgi to get cleaved. Insig will let go of SCAP and SCAP/SREBP complex goes to Golgi.
-Cleavage by S1P and S2P will release bHLH (cutting in the transmembrane domain in a regulated intramembrane proteolysis RIP).
-These causes activation of many genes to produce more LDLR and enzymes involved in synthesis.
So its a pretty amazing to think about. The system is ready to go but has the brakes put on by Insig when cholesterol is high. Its an incredibly fast on/off system becuase everything is alredy make you just need to take the parts to the right location. SCAP is a triple or quadruple function really.
