Lec 1 Cell Membrane Physiology Flashcards
Cell membrane’s General Structure Components:
- phosphilipids - in bilayer
- integral membrane proteins (transmembrane)
- glycoprotein - protein w/ carbo attached
- glycolipid - lipid with glycoprotein
- (BOTH for signalling)
- channel proteins - transport
- cholesterol - fluidity
Lipid Components (3)
glycerophospholipids
cholesterol
sphingolipids
Glycerophosphoipid Components:
fatty acid “tail” 16-18C
* hydrophobic
Glycerol backbone (ester linked to FA tail)
* hydrohpilic
Phosphate ‘head’
* hydrophilic
* Choline (most common), ethanolamine, glycerol, inositol
Cholesterol Components
Steroid
Intercalates between phospholipids - OH to aqueous interface
Impacts membrane fluidity
* small - stiff - decreases fluidity
* larger - increases fluidity
Spingolipid Componets
sphingosine backbone
often sugar residues serving a number of functions
What 2 main structures classes can lipids fit into?
1) fatty acids
2) isoprenoid (make up cholesterol)
Structure of Phospholipid:
1) hydrocarbon chain (hydrophobic fatty acid tails)
2) backbone
* Glycerol (phosphoglycerides)
* ceramide (sphingomyelin)
3) Phosphate-alcohol head group
2 types of phosphoglycerides:
Phosphodiate
* both fatty acids linked by ester link
* more commonly found in cell membrane
Plasmogen
* one fatty acid linked by ester link, other linked by ether link
phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine
- 3 common phosphoglycerides in the cell mambrane
- named based on the functional group attached to the polar phosphate head group! (serine, choline, etc)
Sphingomyelin?
- common phospholipid in membrane
- contains ceramide backbone (why not called phospholipid)
- specific head group - choline
where can glycerol-3-phosphate be derived from?
- addition of phosphate to glycerol (in liver)
- conversion of G3P from DHAP
What step in phosphate synthesis is this?
2 fatty acyl CoA’s added to glycerol-3-phosphate forming phosphatidic acid
Often, fatty acid C1 is saturated and fatty acid C2 is unsaturated
Steps 1 and 2
What step is this in phospholipid synthesis?
Addition of head group (hydroxul first activated by attachment of cytosine diphosphate (CDP))
Step 3
What step is this in phospholipid synthesis?
Modification/Alteration of Head group
(phosphatidylserine and phosphatidylethanolamine - interconvert in reversibel head-group exchange reaction)
Step 4
Phosphatidylinositol?
- less common in membrane
- important in cell signaling
Where does phospholipid syntehsis occur?
primarily on luminal surface of smooth ER and inner mitochondrial membrane
How do newly synthesized phospholipids leave the ER?
- enzyme - flippase
- translocated phospholipids accross ER to cytosolic side
What are steroids?
complex molecules mode from 6 isoprene units
4 fused rings with various substituents
What do you call a steroid with a OH group at C3?
a STEROL
ex. cholesterol
What are the 4 steps in cholesterol synthesis?
- Condensation -** 3 acetyl CoA** into mevalonate
- Formation of isopentenyl pyrophosphate
- Creation of squalene
- Cyclization into cholesterol
What is rate limiting step in cholesterol synthesis?
Step 1 when 3 acetyl CoA’s and condensed into mevalonate - catalyzed by HMG CoA reductase!
How do Statin medications lower cholesterol?
- bloack enzyme HMG CoA reductase - stops cholesterol synthesis
What role does NADH play in cholesterol synthesis?
- is a coenzyme from vitB3 generated in pentose-phosphate shunt
How does Step 2 - conversion of mevalonate to active isoprene isopentenyl pyrophosphate occur?
Addition of 3 phosphates (generated from using 3 ATP)
How many acetyl CoA’s are required to make squalene?
3 acetyl CoA’s in 1 isoprene unit
6 isoprene units in squalene therefore, total 18 are NEEDED
What do Step 3&4 of cholesterol synthesis both require?
NADH
How is cholesterol synthesis regulated?
Through the inhibition of HMG CoA reductase of high intracellular levels of cholesterol
* This is genetic regulation - it blocks the transcription of HMG CoA reductase gene
Reversible covalent modification
* glucagon promotes phosphorylation of HMG CoA reductase - inhibiting it
* (insulin de-phosphorylates it activating the enzyme)