02-11-21 - Lipids in Cell Membranes Flashcards
Learning outcomes
- To explain the importance of membranes in cells.
- To describe the structure of lipid bilayers
- To list the lipid components of bilayers
- To describe what is meant by membrane fluidity and its importance in cell function.
- To describe how a lipid bilayer and cell membrane is formed
- To understand the various ways that proteins may interact with lipids in cell membranes
What is solubility of lipids like?
What are the 3 functions of lipids?
What are the 4 different types of lipids?
- Lipids are molecule that have low solubility in polar substances, like water
- Functions of lipids:
1) Sources of energy – energy stored as fat
2) Formation oof membranes – allows for compartmentalisation in organelles and cells
3) Participation in cell signalling
4 different types of lipids:
1) Phospholipids – make up bi-layer of cell membrane
2) Fats
3) Sterols – makes up a wide range of molecules, including membrane lipids and steroid hormones
4) Some vitamins
What do fatty acids serve as?
What does the structure of fatty acids consist of?
What is the general formula for fatty acids?
What do natural occurring FAs contain?
How are fatty acids most commonly found in the body?
What is an example of this?
- Fatty acids are the principal store of energy
- They consist of a carboxyl group (COOH) with long hydrocarbon chains (fatty acid tails)
- The general formula for FAs is CH3 (CH2)4-24 COOH
- Naturally occurring FAs have an even number of carbons due to the process of their synthesis
- Fatty acids are rarely free in the body, and are more frequently found as part of a lipid molecule, or complexed to a carrier protein
- An example of this are the fatty acids in the blood being complexed to a carrier protein called serum albumin
What happens to short and medium chain fatty acids?
How does this differ from long chain fatty acids?
What are the 2 different types of fatty acids?
How are one of these types found physiologically?
What is the opposite type of fatty acid to this?
How does this type of fatty acid get into the body?
How does it affect health? How do these 2 fatty acids differ?
- Short and medium chain fatty acids can be absorbed into the blood stream
- Long chain fatty acids cannot, and must by synthesised by cells
• Fatty acids can either be:
1) Saturated
2) Unsaturated – contains at least one double bond
- Physiologically, the double bonds of unsaturated fatty acids exist in the cis configuration, meaning the carbons that come off the double bond are on the same side
- Trans fats double bond is found in the trans configuration
- Trans fats can get into the body through diet by eating hydrogenated fats, with trans fat as the by product
- Trans fats are very bad for the health, particularly cardiovascular health
- Cis unsaturated FAs contain a kink in the chain which is not present in trans unsaturated FAs
What are the carbon atoms to double bond ratios in:
• Saturated fatty acids
• Unsaturated fatty acids
• Polyunsaturated fatty acids
How are double bonds in polyunsaturated Fatty acids positioned?
How do delta numbers describe the structure of fatty acids?
What is the structure of omega fatty acids like?
What are omega numbers?
What is an example of this?
- Saturated fatty acids
- Unsaturated fatty acids
- Polyunsaturated fatty acids
- Saturated fatty acids – 16:0 (carbon atoms to double bond ratio)
- Unsaturated fatty acids – 18:1
- Polyunsaturated fatty acids – 20:4 e.g arachidonic acid
- The double bonds in polyunsaturated fatty acids are never conjugated (together)< and are separated by at least one -CH2
- Delta numbers can be used to number double bonds starting from the carboxyl end e.g Δ5 Δ8 Δ11 Δ14 for arachidonic acid
- Omega fatty acids are unsaturated
- Omega numbers are the position of the first double bond in the fatty acid from the methyl end e.g arachidonic acid is omega 6 (Ω)
What 4 things do sterols form the basis of?
Describe the structure of cholesterol
• Sterols form the basis of:
1) Bile acids
2) Steroid hormones
3) Some vitamins
4) Cell membrane – main membrane sterol is cholesterol
- Cholesterol consists of 4 membered rings – 3 6 membered rings and 1 5 membered ring
- This forms a rigid planar structure
- Cholesterol also has a fatty acid tail and a hydroxide group head
What are 4 inherited disorders in lipid pathways?
Which is the most common?
What causes these disorders?
What 4 systems/organs do these disorders largely affect?
What 2 things are these disorders associated with?
1) Gaucher’s disease (most common)
2) Niemann pick disease
3) Tay-Sachs disease
4) Fabry disease
- These disorders are genetic disorders cause by mutations or defects in the genes that code for enzymes
- This results in defects in enzymes which metabolises lipids, which leads to lipid accumulation
These disorders largely affect:
1) The neurological system
2) Liver
3) Spleen
4) Bone marrow
• These disorders are associated with:
1) A failure to thrive/lack of development
2) Reduced life expectancy
What are the 3 membrane lipids?
What are examples of these lipids?
What are their structures like?
• The 3 membrane lipids:
1) Phospholipids – Glycerophospholipids and Sphingolipids
2) Glycolipids - Glycerophospholipids and Sphingolipids
3) Sterols – Cholesterol
- Glycerophospholipids
- Glycerol backbone (3 carbon molecule)
- 2 carbons are attached to fatty acid tails
- These fatty acids tails are a carboxylic group (COOH) attached to long hydrocarbon chains
- 3rd carbon is attached to phosphate and amino alcohol head group (e.g choline)
• Sphingolipids
• Sphingosine backbone, which already has a fatty acid tail
• Sphingosine backbone binds a fatty acid molecule so it has 2 fatty acid tails
• Sphingosines can be:
1) Phospholipids – if the sphingosine backbone binds a phosphate and amino alcohol head group
2) Glycolipid – if the sphingosine backbone binds a sugar head group
- Cholesterol
- Contains a 4-membered planar ring structure (3 6 membered rings, 1 5 membered ring)
- Cholesterol has an aliphatic chain (fatty acid tail)
- Contains Hydroxide group for a head group
What is the main variance in different phospholipids?
What are 4 different amino alcohols found in glycerol backbone phospholipids?
What can the last one be used for? What is the headgroup in sphingomyelin?
- The main variance in different phospholipids is the head group
- 4 different amino alcohols found in glycerol backbone phospholipids:
1) Choline
2) Ethanolamine
3) Serine
4) Inositol
- Inositol can be important for signalling, as the inositol ring can be phosphorylated in different placed
- This can be important for signal transduction
- Sphingomyelin has a sphingosine backbone, with phosphate and choline in the head group
Why membrane lipids described as amphipathic?
Why do phospholipoids form a bilayer when exposed to water?
How are the phospholipids positioned in the bi-layer?
- Membrane lipids are described as amphipathic, as they have 2 different properties in the form of a hydrophilic head and a hydrophobic body
- The conflicting forces between the tail and head of phospholipids drive the formation of a bi-layer
- The hydrophilic heads are attracted to water, while the hydrophobic heads seek to aggregate with other hydrophobic molecules
- The resolution is the lipid bilayer
- The hydrophilic heads face water, while the hydrophilic tails are shielded form the water and lie next to each other
Why is a planar phospholipid bi-layer energetically unfavourable?
What shape does the structure take on?
What does this allow the formation of?
- A planar phospholipid bilayer is energetically unfavourable because there would be planar edges that expose hydrophilic areas to water
- The membrane folds in on itself to form a more spherical structure
- This allows for the formation of a sealed compartment formed by the phospholipid bilayer, where only the hydrophilic aspects of the bi-layers are exposed to the aqueous environment
- This forms an inner and outer leaflet of phospholipids
What 3 reasons are why membranes so important?
1) Membranes allow for compartmentalisation for organelles and cells, where specialised reactions can take place in closed off reaction containers independent of each other
2) Membranes act as selective barriers that control entry into and out of the cell
3) Membranes have sensors that respond to internal and external conditions (sensos are generally proteins)
How is the phospholipid bi-layer described in the fluid mosaic model?
What movement can proteins and lipids of the bi-layer perform?
What are the 2 classes of proteins in the membrane?
Where are they found?
- The fluid mosaic model describes the phospholipid bilayer as a fluid matrix and a 2D solvent
- The lipids and proteins of the bilayer can undergo rotational and lateral movement in any dimension
- The bi-layer is a fluid and lipids can move within the liquid like water molecules in a solution
• 2 classes of proteins in the plasma membrane:
1) Integral proteins (intrinsic proteins) – sits in the middle of the membrane, and spans one side to the other
2) Peripheral proteins (extrinsic proteins) – associated with one side of the membrane, and attached to integral proteins
What are the 2 movements associated with lipids in the membrane?
How common are they?
Why is one type rare?
What is one aspect that controls membrane fluidity?
• 2 types of lipid movement in membrane:
1) Lateral movement – very common
2) Flip flop movement – rare
- Flip-flop movement is rare, as it involved phospholipids moving from one leaflet to another, meaning the hydrophobic tail of the phospholipid would be exposed to water
- Degree of membrane fluidity can be controlled by the status of fatty tails/phospholipids
- Double bonds in unsaturated fatty acids generate kinks in the tail of the structure, allowing for movement to be more fluid and frequent
- Saturated fatty acid tails make the membrane more viscous
What is a lab technique that can measure membrane fluidity?
What are the 4 steps of this technique?
• Fluorescence recovery after photobleaching (FRAP) can be used to measure membrane fluidity
1) Phospholipids are labelled with fluorescent dye
2) Area of cell surface can be bleached, which causes it to lose its fluorescence
3) Measuring the fluorescence in this part of the membrane, it starts to recover. This is because phospholipids and other membrane parts move into this area, and the bleached phospholipids move away
4) The time taken for the fluorescence to recover can be measured – more fluid membranes recover faster
How does cholesterol influence membrane fluidity?
What is the net effect on phospholipids?
- Cholesterol can insert itself into the plasma membrane between phospholipids
- The region where phospholipid is present becomes less fluid, with a more fluid region towards the centre of the bi-layer
- The net effect is that phospholipids become less fluid
How does the composition of the membrane leaflets differ?
Where are phospholipids generated?
Where do the resources to produce these lipids come from?
Where are these lipids placed?
What can then happen to these lipids?
How does the enzyme responsible for this generate asymmetry in composition of the inner and outer leaflet of the membrane?
What are the 2 mechanisms this enzyme can use to perform this function?
- New phospholipids are synthesised by enzymes in the ER that faces the cytosol
- They use fatty acids available in the inner leaflet (cytosolic half) of the bi-layer to synthesise these lipids
- They release the new phospholipids into the inner leaflet of the bilayer
- Lipids are then be transferred to the other leaflet via flippases
- Some flippases are selective for particular types of phospholipids, meaning different types will be concentrated in the inner and outer layer of the membrane, leading to asymmetry in composition
• Flippases can work through the:
1) Pore model – hydrophilic pore is formed
2) Slip-pop model – movement of flippase to move phospholipid from one side to another
Where does membrane synthesis occur?
What happens to newly produced membranes?
What are the 3 steps of this process? What is this process called?
- Membrane synthesis occurs in the ER
- New membrane is then transported to other parts of the cell (organelles or plasma membrane
1) Bits of membrane pinch off from the ER to form vesicles via endocytosis
2) These vesicles then go to Golgi apparatus, where they are sorted and packaged into another vesicle
3) These vesicles can then fuse with other membranes via exocytosis
• This process sis called vesicle trafficking
What 2 things does exocytosis allow?
In what way do vesicles fuse?
• Exocytosis allows:
1) The delivery of lipids and membrane proteins to the cell membrane
2) The movement of other molecules out of the cell
• Vesicles fuse in a way that the leaflets face the same way they did in the vesicle ie inner leaflet facing inside and outer membrane facing outside
What are lipid rafts?
What 2 things do they facilitate?
What do lipid rafts influence?
How do lipid rafts form?
How do lipid rafts sit in the bi-layer?
What can multiple lipid rafts form?
What can be accompany lipid rafts?
• Lipid rafts are specialised regions in the cell membrane which from hubs that facilitate:
1) Vesicle trafficking (endocytosis and exocytosis)
2) Cell signalling (signal transduction)
- Lipid rafts influence membrane fluidity also
- There is more cholesterol in the region where lipid rafts form
- This makes the region stiffer, allowing for more ordered and tightly packed assemblies such as lipid rafts to form
- Though solid, lipid rafts still float freely in the bi-layer
- Lipid rafts can also cluster to form larger, ordered platforms
- There can also be proteins attached/around lipid rafts that have a similar function, or share function
What are 2 things membrane proteins needed for?
What 2 things can this transport be?
What are the 4 types of membrane proteins?
- Many molecules can not diffuse across the membrane, and require specific transport from membrane proteins
- This transport can be active and require energy (e.g endocytosis) or passive and require no energy
- Membrane proteins can also be required for transmembrane signalling between cells
• 4 types of membrane proteins:
1) Transmembrane
2) Membrane-associated
3) Lipid-linked
4) Protein-attached
Where are parts of transmembrane proteins located?
What are they made from?
What can these form?
What do transmembrane proteins tend to contain?
What does this allow?
- Transmembrane proteins can have parts inside and out of the cell or organelle
- They can be made from alpha helices, or beta sheets, which can form a beta barrel (polar channel)
- Transmembrane proteins tend to contain hydrophobic amino acids in them
- These hydrophobic amino acids can marry with hydrophobic regions of the lipid-bilayer, allowing transmembrane protein ns to position themselves within the lipid bilayer
Where can membrane associated proteins be found?
What do membrane-associate proteins usually contain?
What do this allow for?
What is an example of a membrane-associated protein domain?
How long is this domain?
What does it allow?
What happens if this domain is removed?
- Membrane associated proteins can occupy a leaflet in the bilayer, or will be one to the leaflet of the bilayer
- Membrane associated proteins usually contain domains that selectively bind to phospholipids
- This allows for compartment-specific association, which is what is seen in the asymmetric composition of the bilayer
- An example of a membrane-associated protein domain is pleckstrin homology domains (PH), which binds to specific phospholipids
- PH domains are about 100 amino acids long
- Removal of PH domains alters a proteins membrane binding properties
How do lipid linked proteins bind to the bilayer?
Where can they be found?
What is an example of a lipid-linked protein?
- Lipid linked proteins contain lipids which covalently bond to lipids that form part of the bilayer
- They can be intracellular or extracellular
- GPI is an example of an anchoring lipid-linked proteins
- One end of GPIs glycan core is conjugated to phospholipids
What is protein attached proteins associated with?
What are these proteins especially important in?
What is this process?
What is an example of a protein attached protein?
How does it work?
• Protein attached proteins are membrane proteins that are associated with other types of proteins instead of the membrane itself
• PAPs are particularly important in signal transduction
• Signal transduction (aka cell signalling) is the transmission of molecular signals from a cell’s exterior to its interior
• There is a receptor called β2 andrenergic receptor, which consists of 7 alpha helices
• This receptor is bound to by G protein signalling complex, which is a protein attached protein
• When adrenaline binds to the receptor, this changes the properties of the attached G protein in the cell
• The G-protein transduces the signal into the cell, which brings about changes in the cell that lead to events such as:
1) Release of fatty acids
2) Increased cardio muscle contraction
• This increase the amount of oxygen the body gets in order to mediate fight or flight responses
What can form channels/pores in the membrane?
How are these formed?
- Transmembrane proteins can create channels and pores through the membrane
- Hydrophilic amino acids point in the way, while hydrophobic amino acids point out the way, which can form a hydrophilic channel
- Loops that link the structure can have additional structure, which can allow for cell activity for particular molecules to pass through
