Biological Membranes & Lipids Flashcards
How can organelles be separated and why?
Centrifugation
All organelle membranes have different physical and chemical properties
How are organelles separated during centrifugation?
Organelles separated according to their density
The impure organelle fraction is layered on top of a solution that contains a gradient of dense non-ionic substance e.g. glycerol
What is suggested by the fluid-mosaic model?
Lipids in the bilayer form a 2-dimensional sea in which proteins float
What is each surface of the bilayer referred to as?
A leaflet
Why is the membrane fluid rather than a rigid structure?
Due to sideways and lateral movements of proteins and lipid molecules throughout the membrane
What is an integral protein?
What happens when they are removed from the membrane?
They are permanently attached to the plasma membrane
They are embedded within the bilayer so cannot be removed without damaging the membrane
What type of protein is a transmembrane protein?
Integral protein
but not all integral proteins are transmembrane proteins
What is the polarity of integral proteins like and why?
They are embedded in the whole bilayer so must have hydrophilic and hydrophobic areas
Where are peripheral proteins found?
How are they attached to the plasma membrane?
They are on the periphery of the plasma membrane
They are attached to hydrophilic lipid heads by hydrogen bonds or electrostatic bonds
Why can peripheral proteins be extracted without damaging the membrane?
They are not fully embedded in the membrane
How do the lipids in the phospholipid bilayer vary?
There are various types of hydrophilic head group with slightly different functions
There are different lengths of fatty acid tails with different numbers of C=C bonds
How do the headgroups of lipids on one leaflet of a membrane relate to the other leaflet?
The headgroups of lipids on one leaflet is different to the opposite leaflet
What is significant about the asymmetry of the 2 membrane leaflets?
The percentage difference between the headgroups on each leaflet
What can alteration of lipid asymmetry lead to?
It plays a role during:
- cell fusion
- activation of the coagulation cascade
- removal of apoptotic cell corpses by macrophages
What is a lipid raft within the bilayer?
This is where a patch of the membrane is different from the bulk composition
What is the largest group of lipids?
What forms the link between the hydrophobic and hydrophilic parts of the lipids?
Glycerophospholipids
The glycerol-3-phosphate backbone is the link between the hydrophobic and hydrophilic parts of the lipid
How do fatty acid chains attach in glycerophospholipids?
There are 2 fatty acid chains
They form ester bonds to the hydroxyl groups of glycerol
What bonds are formed from the phosphate group of the glycerophospholipid?
It forms a diester with the glycerol and with a specific head group
How many carbon atoms do normal fatty acid chains contain?
How are they synthesised?
They have an even number of C atoms
They are made by the stepwise addition of acetate (2C), which is carried to the reaction by coenzyme A
How many glucose molecules are consumed in fatty acid synthesis?
Per 6 carbons added to the fatty acid chain, 1 glucose is consumed
What enzymes are needed in fatty acid synthesis?
Fatty acids are created from acetyl-CoA and NADPH through the action of fatty acid synthetases
What determines the naming of a glycerophospholipid?
the nature of its headgroup
e.g. if choline is the headgroup, it is phosphatidylcholine
What is the role of phosphatidylinositol?
It has a key role in intracellular signalling in response to hormones
What is the role of phosphatidic acid?
It is an important signalling lipid, especially in the CNS
It helps maintain membrane composition
What is the role of amine groups within a cell?
They are involved in cell signalling
They must be cleaved from the lipid to act as signalling molecules
What is the role of phosphatidyglycerol?
It is NOT a signalling molecule
It is an intermediate in biosynthesis of cardiolipin
What is cardiolipin and what is it involved in?
It is a component of the inner mitochondrial membrane
It is required for the functioning of enzymes involved in oxidative phosphorylation
What is the overall charge of the membrane and why?
Only charges that are added to the headgroup can compensate for the strong negative charge of the phosphate group
The overall charge will always be negative
Why does the bilayer have some fluidity?
there are no covalent bonds between lipids in a bilayer
How can lipids move within a bilayer?
They can rotate on their axis
They can move laterally along the same side of the bilayer
By which process do lipids flip unaided from one side of the bilayer to the other?
How fast is this process?
Transverse diffusion
Very slow to occur as hydrophilic headgroup would have to move across hydrophobic interior
Energetically unfavourable
What enzymes are involved in segregating lipids to the correct leaflet in the first place?
Translocase enzymes
They flip the phospholipids across the membrane in an energy-dependent fashion
What is the difference between a flippase and a floppase?
A flippase transports lipids from the exoplasmic face to the cytosolic face
A floppase transports lipids from the cytosolic face to the exoplasmic face
What is the role of translocase enzymes?
They assist in moving a molecule across the membrane
e.g. flippases and floppases
What molecule is involved in moving phosphatidylcholine across the membrane?
phosphatidylcholine translocator ABCB4
What happens if phosphatidylcholine translocator ABCB4 is faulty?
What are the symptoms?
Progressive familial intrahepatic cholestasis
- fat malabsorption
- fat-soluble vitamin deficiency
- osteopenia
What is the role of scramblase enzymes?
they randomise the normal membrane distribution of lipids
they undo the work of translocases
When are scramblases activated?
They are usually switched off
They are activated when the calcium concentration inside the cell increases
e.g. when platelet is activated
How does blood clotting involve the activation of a scramblase?
- scramblase moves a phosphatidylserine molecule to the outside of the cell membrane
- this allows the phosphatidylserine to interact with blood clotting factors on the surface of the platelet
What is the process leading to apoptosis?
Cell membrane asymmetry is lost when phosphatidylserine residues are moved to the external leaflet
This is done by a scramblase
What is the process involved in apoptosis?
- proteins called caspases are activated
- caspases break down cellular components needed for survival and trigger production of DNAses
- DNAses destroy all the DNA within the nucleus
- the cell shrinks and sends out distress signals that are recognised by macrophages
What is the result of the cis double bond in the fatty acid chain attached to carbon 2 of glycerol?
It results in a kink in the chain
The fully saturated chain attached to C1 is straight
What is the result of having a kink in an unsaturated fatty acid on the membrane?
It contributes to the fluidity of the membrane
This is because the kinked phospholipid chains pack more loosely
What is the state of membranes at room temperature and why?
They are semifluid
This is due to the combination of both saturated and unsaturated fatty acids
What happens to membranes in frostbite?
Membranes solidify at cold temperatures
Frostbite damage occurs when oxygen can no longer diffuse through solidified cell membranes
The outermost (coldest) cells die
What are desaturases?
How many are present in mammals?
They are enzymes capable of introducing a double bond into fatty acids
There are 4 different types
What is the action of delta-9 desaturase?
it introduces a double bond at the 9th carbon atom from the carboxylate end
What happens to the fatty acids whilst desaturation is taking place?
they are esterified to the carrier molecule - coenzyme A
They are released from CoA afterwards
Why are some fatty acids needed to be taken in from the diet?
Humans can desaturate fatty acid chains at some positions in the acyl chain, but not at others
How long is the carbon chain made by fatty acid synthetases?
They stop at 16-18 carbons
Other modifications must occur to extend the FA chain further
How does a sphingolipid differ to a glycerophospholipid?
They have a sphingosine molecule as their backbone, instead of glycerol
What is the sphingosine comprised of?
Where are sphingolipids found?
It is a long chain of 18 C atoms
They are found in the brain and nervous tissue
What is the role of sphingolipids?
They are believed to protect the cell surface from harmful environmental factors
What is the structure of cholesterol like?
It has a rigid, compact, fused ring structure attached to a less rigid aliphatic chain
Where are the polar and non-polar parts of cholesterol positioned?
They hydrophobic group is integrated deeply into the membrane
The polar hydroxyl group is exposed to the aqueous environment surrounding the cell
What are lipid rafts made from?
Sphingolipids packing close together with cholesterol
How do lipid rafts tend to differ to the composition of the rest of the membrane?
They are very compact and usually thicker
This is due to long, saturated fatty acid chains attached to the sphingolipid
What is the function of lipid rafts?
They serve as signalling platforms in a number of cellular processes
What neuronal diseases are linked to lipid raft alterations?
- smith-lemli-opitz syndrome
- huntingdon’s disease
- alzheimer’s
- niemman-pick type c
What autoimmune diseases are linked to lipid raft alterations?
- lupus erythematosus
2. rheumatoid arthritis
What is the relationship between virus particles and lipid rafts?
The membranes can form caveolae and invaginate
This is a way in which viruses can be internalised into cells
What is the protein involved in caveolae formation
Caveolin
What happens when something attaches to a lipid raft that is to be taken up by the cell?
The lipid rafts accumulate and caveolin accumulates to form vesicles
What are gangliosides?
They are a family of membrane sphingolipids
They have sugar groups attached to the sphingosine
What happens when sugar molecules are added to proteins and gangliosides?
This occurs in the ER
Vesicles containign the newly synthesised proteins bud off the ER and travel to the Golgi
Further sugar residues are added to make branched antennae structures
What happens after the glycolipids/gangliosides leave the Golgi?
Vesicles bud off the Golgi and fuse with the plasma membrane
The vesicles release some of their protein content outside the cell
Glycolipids remain in the vesicle and membranes
What happens to glycolipids during endocytosis?
Reinternalised during endocytosis
Vesicles fuse with lysosomes where some of the sugar tree is trimmed back
What is the role of glycolipids in blood grouping?
The branched glycan attachment is a recognition site for the immune system
This is in the ABO blood grouping
What does ganglioside deficiency lead to?
Inflammation and neurodegeneration via the activation fo the complement system in the spinal cord
What property of cholesterol and phospholipids means that they can form membranes?
They are amphipathic
They have both hydrophobic and hydrophilic parts
What is the role of most neutral lipids?
How does their structure differ to membrane lipids?
They have no polarity as the head group is replaced with a fatty acid
They are storage lipids
What are the storage lipids?
Triacylglycerols and cholesterol esters
What do storage lipids form within cells and why?
They are found in nearly every cell and produce a compressible cushion within the cell
They store energy as densely as possible
How are storage lipids associated with phospholipids?
They have one layer of phospholipids around them to help organise the neutral lipid within the cell
