Lecture 9 cell membranes Flashcards
Why are lipids important?
There is no cellular life without lipids!
-The plasma membrane separates the cellular contents from the outside
- Internal membranes separate the contents of different organelles from the rest of the cell
-No membranes, no gradients, no energy!
-Membrane lipids are amphiphilic and they associate to form a permeability barrier that most solutes cannot freely diffuse across
+Water-loving polar head groups interface with the water
+Water-hating fatty acyl chains associate with each other
Does size and shape matter in lipids?
- YES in long chain fatty acids
- makes them flexible/inflexible
- Size, shape and amphiphilicity is everything to a membrane lipid
- Glycerophospholipids, Sphingolipids and cholesterol are the main classes of membrane lipids
What are some characteristics of membrane lipids?
- The amphiphilicity of membrane lipids means that they readily self-associate in water
- Their cylindrical shape means that they favour a bilayer of two leaflets, rather than a micelle
(fatty acids=conical/membrane lipids=cylindrical)
3.The propensity to form membrane sheets favours the formation of Liposomes (membrane lipid balls) (more energetically favourable)
What can liposomes be used for and what are exosomes?
- Liposomes can be used to study the behaviour of lipid membranes (and, because they are readily taken up by cells, have also been used to deliver drugs and DNA to patients)
- Exosomes (liposomes released by cells and containing cargo) are a recently discovered form of cell to cell communication.
Describe the fluid mosaic model.
+The fluid mosaic model (Singer and Nicolson, Science 1972) describes the membrane as a 2-D fluid (BUT SHOULD BE UPDATED!)
-Acyl chains can flex within the bilayer
-Membrane lipids can rotate within the bilayer
-Membrane lipids can diffuse laterally within the leaflet
-Flip-Flop, the movement of membrane lipid from one leaflet to the other is rare (but can occur rapidly in certain cell types under certain conditions)
+The major lipid components of most biological membranes are also arranged asymmetrically between the two leaflets of the bilayer
What are the several major lipid components with different chemical nature that comprise membranes?
-Glycerophospholipids: \+amino-phospholipids \+choline phospholipids -Sphingolipids: \+choline phospolipids \+glycolipids
What is cholesterol comprised of?
- polar head group
- rigid steroid ring structure
- non polar hydrocarbon tail (in that order)
What effect does cholesterol have on the membrane?
- Head group hydroxyl of cholesterol associates with the head group of the neighbouring glycerophospholipid
- Steroid ring and acyl chain intercalate with the acyl chains of the glycerophospholipids
- Add cholesterol to a glycerophospholipid bilayer and it becomes more densely packed, less fluid and less permeable (more RIGID!)
- Cholesterol intercalation reduces packing density of sphingolipids and keeps membrane more fluid
- Cholesterol therefore modulates the behaviour of the membrane dependent on the other lipids it interacts with
- Cholesterol is enriched along with sphingolipids in membrane invaginations (caveolae and clathrin-coated pits) that are important for endocytosis
What are lipid rafts?
+membrane domains enriched in Sphingolipids and Cholesterol
- This may suit the fold and function of some membrane proteins over others
- Different lipid and protein content = specialised function
- Lipid rafts bring together proteins that work together e.g. for endocytosis or signalling
What else does cholesterol do except for its membrane functions?
-Bile salts
+Solubilisation of dietary fat and lipophilic vitamins
+Liver
(1/4 of cholesterol synthesized from acetyl-coA in the liver)
-Vitamin D
+Skin
-steroids:cortisol,aldosterone
+Adrenal gland
-sex hormones:progesterone,oestrogen,testosterone
+Testes and ovaries
How is cholesterol stored?
-Cholesterol esters are stored in fat droplets
-FAs are stored primarily as triglycerides (triacylglycerols)
+Efficient: 1g triglyceride = 6x energy store of 1g glycogen, and occupies less volume
(but it is slower to catabolise; marathon runners as they ‘hit the wall’ have used up their carbohydrate reserves and are catabolising mainly fat)
-Fat droplets: the only organelle surrounded by a lipid monolayer
- Droplet originates from the ER and is bound, unusually, by a membrane lipid monolayer because its contents are hydrophobic
What do Glycolipids do and what are they made of?
+Made of:
-Based on ceramide
-Contain sugar head groups
-NANA (sialic acid) carries a negative charge
-Confined to the outer leaflet of pm
-GM1 ganglioside is the receptor for cholera toxin
+Function:
-Protect the cell from hostile environment (circulating proteases, lipases, low pH)
-Important in cell-cell contact (via lectins; membrane proteins that bind sugars)
-Localise to and may be important in lipid raft
generation/function!
(Ceramide is serine with two acyl chains (serine with one acyl chain is sphingosine). Mice deficient in all gangliosides are fine apart from an inability to transport testosterone normally in the testes and are therefore sterile)
Is the lipid composition of all cells the same?
- NO
- Different organisms/cells/organelles have different lipid composition. The different chemical nature of the lipids they contain is related to the different functions of the organism/cell/organelle
1. Hepatocytes are enriched in PC because they secrete PC into the bile
2. The ER is low in cholesterol and its lipids are primarily glycerophospholipids that are arranged symmetrically making it more fluid (for membrane protein insertion)
3. E. coli lacks cholesterol; Gram –ves have a double membrane, with peptidoglycan to provide stability
4. Myelin is enriched in glycolipids – which insulate the nerve axons (important for nerve impulse conductivity)
What are lipid anchors?
Membrane proteins interact with the membrane in different ways
- Lipid anchors = long chain fatty acids and a cholesterol intermediate
- Lipid anchor from fatty acids myristic, palmitic or prenyl group (farnesyl). Most membrane proteins cross the membrane with alpha helices
- All are reversible by proteolysis (or de-esterification) and lipid transferase. Can be used to recruit proteins to, or detach proteins from the membrane
What role do alpha helices play in membrane proteins?
- Most eukaryotic integral membrane proteins cross the membrane as α-helices
- Transmembrane α-helices are enriched in non-polar/hydrophobic amino acids
