Lipids Flashcards
membrane composition
Lipids: phospholipds (sphingolipids (SM), PC, PE, PS, PI), cholesterol, glycolipids
Proteins (specific to membrane type)
Lipid/protein content in different membranes
- variable between different membranes
- constant for specific membrane
Myelin: 75% lipid, 25% protein
RBC: 40% lipid, 60% protein
IMM: 20% lipid, 80% protein
RBC plasma membrane lipid types
40% lipids:
cholesterol 15%
phospholipids 25% (mostly PC and SM since they’re choline lipids)
50% of lipid mass is unsaturated fatty acids
amphipathic
has both hydrophobic portion and hydrophilic portion
temperature/fluidity and phospholipid bilayer
- affected by fatty acid chain length and degree of unsaturation
- longer chain=higher melting temperature
- more unsaturation=lower melting temperature
Cholesterol in bilayer
- modulates membrane fluidity
- -OH on outside of membrane
Lipid distribution on cytoplasmic vs extracellular layer of bilayer
- asymmetric distribution of lipid types on inside and outside
- lipids can diffuse along same layer (lateral) or can move from inner to outer or from outer to inner (transverse)
protein flipase
can aid in transverse movement of phospholipids from one side of bilayer to the other
RBC plasma membrane inner/outer lipid distribution
-inner mostly PS and PE
-Outer mostly PC and SM (choline containing)
More choline on outer surface
Integral/intrinsic proteins
- detergents to isolate
- hydrophobic
- structural role
- pumps/transporters, receptors, enzymes
Peripheral/Extrinsic proteins
- pH, ions to isolate
- hydrophilic
- enzymes, cytoskeletal protein
RBC proteins
- isolated after osmotic shock
- Extrinsic/peripheral proteins: spectrin, ankyrin, actin, band 4.1 and 4.2
- intrinsic/integral: band 3 (anion transport), glycophorin, G3PD
Glycophorin
- first membrane protein ever sequenced
- antigen
- abundant in RBC
- N terminal 70aa outside cell with sugars
- 23 apolar aa in transbilayer domain
- 38aa at c terminus is internal charged domain
Width of bilayer
35A
23amino acids
(1.5A is rise/residue of alpha helix, 1.5*23=~35A)
plasma lipoproteins
- complex of lipids and specific proteins (apolipoproteins)
- used to solubilize fat and transport in blood
- 4 major types: chylomicrons (CM), very low density (VLDL), low density (LDL), high density (HDL)
FA storage
- FA stored at triglygerides
- TG broked down into FA and glycerol by lipase
- FA uptake by cell
- FA used as energy, stored, restored back to TG, or beta oxidized
Cholesterol ester
- for storage/transport of cholesterol
- cholesterol coupled with FA to make cholesterol ester
CM composition/location
- 90% TG
- B, C, E apoprotein classes
- 2000A big
- from intestine
- removed from blood in adipose tissue/liver
VLDL composition/location
- 65% TG
- B, C, E apoprotein classes
- 600A medium sized
- from liver
- removed from blood in adipose tissue
LDL composition
- 50% CE
- B class apoprotein
- 200A small
- from VLDL catabolism
- removed from blood in liver and peripheral cells
HDL composition
- 20% CE, 25% PL, 50% protein
- A class apoprotein
- 100A very small
- from liver and removed from blood in liver
LDL function
cholesterol delivery (bad)
HDl function
for cholesterol removal from cells and body (good)
Lipoprotein lipase (LPL)
- plasma enzyme
- breaks TG into FA
- Apo-C is coenzyme
Lechithin cholesterol acyl transferase (LCAT)
- plasma enzyme
- takes FA from phospholipid to make CE
- Apo A is cofactor in bloodstream
Acyl-CoA cholesterol acyl transferase (ACAT)
takes acyl-CoA and cholesterol and makes CE
inside liver cells
HMG-CoA reductase
makes cholesterol, rate limiting step in cholesterol synthesis
regulates body cholesterol
Apolipoproteins
- Apo A: LCAT cofactor, ligand for ABC-A1 and SRB1
- Apo B: ligand for LDL receptor
- Apo C: LPL cofactor
Biological microemulsion
droplet of fat (TG/CE) at core, coated with phospholipid monolayer dotted with apolipoproteins for stability and enzymatic function
Cholesterol in the liver
Cholesterol synthesis (FA–>TG)
some cholesterol –> CE
some cholesterol –> bile (only way to remove from body)
Familial hyperchosesterolemia
genetic disease resulting in inability of cells to take up cholesterol by LDL and high cholesterol in bloodstream
Receptor mediated endocytosis
- LDL receptors cluster causing ‘fatty coat’ on outside of cell
- clatherin coat formed and makes invagination of plasma membrane
- vesicle endocytosed, merge with endosome to disocciate receptor/LDL
- receptors recycled to cell surface
- Apo B and CE broken down in lysosome to aa and cholesterol/FA respectively
- cholesterol used for membrane biogenesis, steroid hormones (in adrenal gland), bile acids (in liver) or put in storage as CE (via ACAT) which turns off HMG-coa reductase and stops cholesterol synthesis
Reverse cholesterol transport
Only method of cholesterol removal
- ABC-A1 transports cholesterol and PL out of peripheral cell (with Apo A as ligand)
- LCAT converts cholesterol to CE in nascent HDL
- mature HDL formed
- CE selectively taken into liver cell by SRB1 (using apo A as ligand)
- CE in liver to bile acid synthesis or secreted into bile for removal.
