Membrane structure and function Flashcards
Membrane structure and synthesis
what does the membrane define?
3 key features of a membrane?
what are they defined by?
4 roles of membrane?
Define boundaries between cells and within cells
Flexible
Self-sealing
Selectively permeable
Defined by their molecular composition Transport Cell recognition Cellular communication Metabolic regulation
Why are biological membranes bilayers?
what are they largely composed of?
what is special about the lipids?
how do they assemble? bonds?
Biological membranes are composed largely of lipids and proteins
The lipids are amphipathic meaning they have a hydrophilic and hydrophobic part
Assemble spontaneously
Non-covalent assemblies
common features that membranes have (7)
thickness? form where? consist of? what is special about this? bonds? symmetry? transport? how?
- Two molecules thick
- Form closed boundaries of the cell,
- Consist of lipids and proteins
- Contain specific proteins
• Which mediate distinctive cell functions. - Non-covalent arrangement
- Asymmetric, it is also known as fluid-mosaic model.
- Membranes are electrically polarised
• Key role in transport.
Lipid composition
in general what do they all consist of?
what are the main lipids? (3)
what is a sphingomyelin?
what does cholesterol in the membrane regulate?
in general all consist of a hydrophilic head and a hydrophobic tail.
The main lipids are phospholipids with the phosphate head, cholesterol with a –OH head and glycolipids with a large carbohydrate head on the outside and a lipid group in the membrane. Sphingomyelin has choline at the end.
Cholesterol in the membrane regulates membrane fluidity
Amphipathic lipids
what 2 lipids are amphipathic?
what do they both readily form in aqueous medium?
what do they have to ability to form? 2 clinical uses for this?
Phospholipids and glycolipids are amphipathic.
They both readily from bimolecular sheets (bilayer) in aqueous media and they ability to form liposomes might have clinical uses such as the delivery of drugs or DNA.
Membrane Synthesis
where is the new membrane made/surface? what does this cause? what needs to be done?
how is redistribution done and what is needed? why are these needed? what will this lead to?
where are these largely associated with for the synthesis of membrane?
where may sythesis ER lipids be altered? 2 exceptions to this?
what happens as new lipids are inserted?
what must act on this and what is the effect of this?
- New membrane is made on the cytosolic surface of the ER causing enlargement on one surface which is not desirable and therefore will be redistributed.
- Redistribution is done by several enzymes. Enzymes are needed for this due to the strong interactions between the hydrophilic head and hydrophobic tail. This leads to the correct asymmetry of the membrane.
- Enzymes responsible for the synthesis of membrane phospholipids are associated largely with the cytosolic side of the ER.
o Synthesis ER lipids may be altered as the membranes flow from the ER to Golgi to vesicles.
o Exceptions sphingomyelin and glycolipids started in ER and finished in Golgi
As new lipids are inserted, the bilayer starts to bow as one side gets more enlarged. Flippase then flips lipids from one side to the other so that both sides get enlarged and the membrane is no longer bowed but straight.
Membrane synthesis enzymes
what 3 enzymes are involed?
what are their roles?
Floppase - moves phospholipids from the inner to the outer leaflet (requires ATP)
Flippase (flipase) – moves phospholipids from the outer to the inner leaflet (requires ATP)
Scramblase – bidirectional movement
Summary of above flashcards
special feature of membrane lipids? 3 major classes of lipids? what happens to lipids in aq? where does phosholipid sythesis take place? what does distribution require?
Membrane lipids are amphipathic
Major lipid classes are phospholipids, glycolipids and cholesterol
Lipids spontaneously form bilayers in aqueous solutions
Phospholipid synthesis takes place on the cytosolic surface of the endoplasmic reticulum
Distribution of newly formed lipid requires the enzymes flippase and floppase
Highly unfavourable for the charged heads to move so how do they do it?
via ABC transporter (ATP-binding cassete transporters) so charged heads can move through hydrophobic region
Membrane fluidity
fast mivement of lipids?
slow movement of lipid? why? what does it require?
Membranes are fluid.
Lipids can move across the surface (Lateral movement/diffusion) rapidly.
Transverse movement/ diffusion is slow, rarer & requires the action of the enzyme Flippase. (More energy to get the hydrophilic head through the fatty membrane
Factors that alter fluidity
5 factors that alter fluidity?
affect of saturation? chain length?
Factors that alter fluidity are:
- Temperature
- Fatty acid composition
- Chain length
- Degree & extent of saturation
- Cholesterol content
Saturated fatty acyl chains increase rigidity as the lipids pack together, meaning there are stronger interactions. Increased length increases rigidity as there are increased interactions between the chains
Cholesterol & temperature
what happens to membrane at low temp? what does cholesterol do low temp? hence effect?
what happens to membrane during high temp? what does cholesterol do high temp? hence effect?
- Temp is low, energy of molecules is low, motility of membrane decreases (Move closer together), less fluidity
- Low temp, cholesterol (Small numbers) interferes with the interaction between phospholipids & increases membrane fluidity.
SO low temp, the chokesterol INCREASE fluidity
- Higher temp, energy associated with molecules is greater so the spaces between molecules increases and therefore fluidity of the membrane increases
- High temp, cholesterol (Greater numbers) works to stabilize the membrane & reduce membrane fluidity by bringing phospholipids closer together
SO high temp, cholesterol DECREASE fluidity
affect of cholesterol
- Cholesterol maintains the membrane and tries to get it back to normal composition during changes in temperature.
Spur cell anaemia
what is abnormal? effect of this?
what does it lead to?
In people who have SCA their cholesterol content is increased by 25-65%, this very high amount of cholesterol eventually decreases membrane fluidity.
This leads to spikey RBC which are fragile and obstructive -> ruptures .
Membrane Asymmetry
why?
Membranes are asymmetrical (cytosolic side of the membrane is different from the ECF side). This is true of all membrane, not just plasma membranes.
Fluid Mosaic model
5 key features?
Flexible Self-sealing Selectively permeable They define boundaries Divide the internal spaces
Integral membrane proteins
what do they span? can they be removed? single or multi? bonds? protein structures involved? where do r groups face? why?
Integral membrane proteins span the entire membrane
it is very difficult to remove them from the membrane
Single or multi pass
Strong non-covalent bonds
Trans-membrane domain often an a-helix
R groups in the being hydrophobic in nature facing outwards in the membrane.
can be predicted from sequence
Peripheral membrane proteins
where are they located?
how are they associated with it?
what are they bound to?
how are they bond? hence?
These are located on the extracellular or cytosolic membrane surface and are loosely associated with it, but not embedded just bound to a phospholipid polar head group or integral membrane protein.
They are associated by non-covalent bonds to the surface, as the association is not that strong they associate transiently with the membrane. (so easier to remove these proteins)
Lipid anchored membrane proteins
bond? to?
These proteins are covalently linked to a lipid molecule such as glycerol phosphatidylinositol.
tightly associated + covalently linked proteins
Membrane Carbohydrates
what are they associated woth? how much of membrane weight? % what are majority facing? what are they often involved in? (2) what are blood group antigens? how much of rbc weight is carbs? % what are selectins?
Carbohydrates are associated with both membrane lipids and proteins
Form 2-10% of the membrane weight
The majority of glycolipids and glycol proteins are externally facing
They are often involved in cell-cell interactions or cellular recognition
The blood group antigens are glycolipids
In RBCs 8% of the weight is carbohydrate
Selectins are an important group of membrane glycoproteins
membrane functions
plasma membrane? mitochondira? ER? Golgi? nuclear membranes? lysosomes? peroxisomes?
Plasma membrane = Barrier, transport, signal transduction
mitochondria = Energy transduction and Barrier
ER = Translation protein processing and Synthesis of complex lipids
Golgi = Post-translational modification + Processing for secretion
Nuclear membranes = Attachment of chromatin
Lysosomes = Hydrolytic enzymes
Peroxisomes = Fatty acid oxidation
Chemical Composition of some cell membranes
what does chemical postion change?
2 examples of rich chemical membranes?
Specific functions have meant that the structures are different.
Membrane function is dependent on structure and the chemical composition of cell membranes varies.
-> Some are very rich in lipid (e.g. myelin) while other are very rich in protein (e.g. inner mitochondrial membrane).
Membrane Permeability
how permeable is it?
what can move in through simple diffusion?
what can’t move in via this way?
The plasma membrane is semi-permeable:
- Lipid soluble molecules e.g. N2, O2 and small uncharged polar molecules like Urea, H2O, glycerol, CO2 can move either way through the membrane and the movement of these molecules is dependent on their concentration.
o This is called simple diffusion - Large uncharged polar molecules e.g. glucose and ions e.g. H+, Na+ cannot diffuse through by simple diffusion
Membrane transport
different ways molecules can move in?
Membrane transport can be passive or active and it can be non-mediated (i.e. molecules just moves through, could be straight through the membrane or a channel, passive) OR it can be carrier mediated (could be passive or active).
Membrane Transport
Co-transport
what is this? what are the 2 types?
Co-Transport is when a transporter moves two molecules at the same time, this can be an antiporter (moving molecules in opposite directions) or a symporter (moving them in the same direction), this would be used to generally get one target molecule through using the concentration gradient of another.
Carrier mediated facilitative diffusion vs simple diffusion
2 similarities
3 differences
Both are driven by concentration gradient
Both require no energy
Carrier mediated is specific
carrier mediated is faster
carrier mediated can get saturated but diffusion has no limits
Glucose Transport
what kind of diffusion is this? why?
what trnapsort glucose?
what does the Kt value tell us? lower number means?
Carrier Mediated facilitative diffusion
Glucose transport is carrier mediated, it cannot get through quick enough by simple diffusion.
- It can be passive (by facilitated diffusion) or active (by sodium symporter).
- If there was no carrier, glucose transport would be incredibly slow, the carrier mediated facilitated diffusion speeds up the rate of glucose transport greatly.
There is a family of glucose transporters (GLUT transporters), these each have their own tissue locations and a Kt value (same as Km), which tells us the affinity of the transporter for glucose.
The higher the affinity = lower Kt value = the more readily it’ll bind to glucose.
Circulating concentration of glucose
Resting 4mM
After a meal 10-15mM
what glut transporters are active here?
At rest, GLUT 1 and 3 active and goes to all mammalian tissue
after food, GLUT 2 and 4 active hence used for muscles and insulin
How do a carrier mediated transporters function?
what results in transport?
what drives this?
what direction is it?
example as glucose
what happens when glucose binds?
how does body maintain conc grad with glucose?
why does this work?
how can glusoe uptake be increased?
Membrane Transport Facilitated Diffusion: This is where conformational changes in the membrane protein result in transport, it is driven by the concentration gradient. Transport is bidirectional, it can go either way.
In action -> The transporter binds to glucose and it then undergoes a conformational change -> this opens the inner portion to the cytoplasm and the glucose diffuses in.
Because the transport of glucose is driven by the concentration gradient of glucose, the way the cell maintains this gradient is by the moment the glucose enters it gets phosphorylated.
The kinetics of glucose transport is similar to enzyme kinetics, firstly the transporter is specific for the molecules they transport (i.e. D-glucose, not L-glucose).
The interactions exhibit saturation type kinetics and they can be regulated. So glucose is converted into glucose 6-phosphate to remove the gradient from the inside so continous transport
Importantly, glucose uptake can be increased by increasing the number of transporters on the cell surface, for example the GLUT4 in adipocytes and skeletal muscle stimulated by insulin.
Active transport
Na+
what does active transport require apart from atp?
what establishes the conc grad?
An example of active transport would be Na+, the concentration of Na+ outside cells (around 140mM) is higher than inside the cells (around 15mM), but there is no free movement as they cannot get through the membrane.
- Like facilitative transport, active transport is selective and requires an integral membrane protein.
Sodium is linked to antiport system with potassium, the protein that does this is a Na+/K+ ATPase.
- It requires energy in the form of ATP to work. It pumps 3 Na+ out for every 2K+ in, this is what establishes the concentration gradient between inside and outside.
Fox glove
what does this do? where?
effect of this? why?
Foxglove contains the chemical digitalis, which is a cardio tonic steroid which inhibits the Na+/K+ pump.
- This increases the force of contraction of the heart, so is the treatment of choice for congestive heart disease.
- The reason it does this is because inhibition of the pump leads to increased intracellular Na+ which thus leads to slower removal of Ca2+ by the Na+/Ca2+ exchanger, resulting in increased ability of the muscle to contract.
Sodium dependent glucose transporters
what are the dodium dependent glut transporters? (2)
how do they work?
what happens to glucose? how is Na+ gradient maintained?
- Sodium dependent glucose transporters are SGLUT-1 and 2. These are symporters which will only work if you have both Na+ and glucose bound, once both are bound both will be transported into the cell.
- This by itself is a passive process, the glucose gets phosphorylated while Na+ is pumped actively out by the Na+/K+ ATPase in order to maintain the Na+ concentration gradient.
- Hence, because of this, the SGLUT-1 and 2 would be said to be indirectly active processes because they rely on this concentration gradient brought about by an active process.
Cellular Asymmetry
what does this allow?
example?
what is present on gut side?
what is present on other side of the cell?
how is assymmetry maintained? what does this prevent?
Cellular Asymmetry allows transport of molecules, as can be seen in the picture below, the SGLUT-1 is a Na+ driven glucose symporter.
- Present on the gut lumen side of the enterocyte, this transports glucose from area of lower concentration to an area of higher concentration using the concentration gradient of Na+.
On the other side of the cell facing the extracellular fluid, the basal domain is the GLUT -2 which transports glucose down its concentration gradient from higher in the cell to lower in ECF.
The Na+/K+ ATPase pump also works down here.
Assmmetry is maintained by tight junctions between adjacent cell plasma membrane is tight so prevent re-distribution of transporter
Rehydration Therapy
what does it target? why?
what is absrobed from gut? (2) effect of this?
Targets the co-transport of glucose and sodium to combat the loss of water, electrolytes and loss of food nutrients during diarrohoea
Na + glucose absorbed from gut
glucose used for energy
Na will draw in water and rehydrate the individual
Gated channels
what are they?
how are they activated? (3)
Transmembrane proteins that form pores for the movement of ions
Activated/opened by different stimuli including:
voltage
ligand
phosphorylation
Transport proteins are also associated with disease
Chloride channel and Cystic fibrosis
deletion where?
if inviduals carry deletion in both copies of genes, what happens?
1 in 20 Caucasians are carriers of a single deletion at position 508
individuals that carry the deletion in both copies of the gene produce a protein that fails to insert into the membrane hence cystic fibrosis
Compartmentalization
what 4 things does this allow?
Compartmentalisation separates reactions, enables the local environment to be regulated (for instance pH) and helps to bring reactants together.
Enables electrochemical gradients to be established
A disease of misdirection
Compartmentalization
how do proteins get to their specific compartment? if this changes, what happens?
name an exception where this isnt used as the target. what is the target in this case?
if individuals are deficient in the phosphotransferase enzyme, what happens? where will it appear?
what makes lysomes an acidic environment?
Proteins get to their specific compartment via signal sequences, which target them to specific organelles. This signal sequence can be changed to make a protein go into a different compartment.
Not all proteins are targeted using their amino acid sequence, lysosomal enzymes are targeted by the carbohydrate mannose-6phosphate.
Individuals that are deficient in a phosphotransferase enzyme present in the Golgi cannot modify the mannose sugar that is normally present on enzymes targeted to for the lysosomal enzymes, and thus they appear in the blood and urine. Various diseases are caused by the inability of the cell to target the enzyme to the lysosome.
Lysosomes are an acidic environment due to the proton pump that pumps H+ into the lysosome.
Membranes and Environment
3 key roles when interacting with environment?
what recognise hormones and neurotransmitters?
what involved in cell recognition? 2 examples of this
cell communication, apoptosis and cell to cell recognition
Receptors will be present on membranes for hormones and neurotransmitters
Membrane carbohydrates are involved in cell recognition, such as blood antigens which are glycolipids, lymphocyte trafficking down blood vessel wall by selectins -> requires a type of glycoprotein.
Apoptosis
what do they do?
what is the marker? where is it usually? how does this change?
Cells that want to undergo programmed cell death display eat me signals for macrophages on their plasma membrane cell surface.
- Phosphatidylserine is this marker, usually it will be on the inside of the membrane but will undergo the transverse diffusion when needed and exposed on the surface.
