Session 1 - Lipids, Proteins and Membrane Structures Flashcards
Welcome to Semester 2 guys!
Functions of membranes? (5)
- Continuous, highly selective, permeability barrier
- Control of enclosed chemical environment
- Communication between cells and their environment
- Recognition e.g. signalling proteins, adhesion proteins, immune surveillance
- Signal generation in response to stimuli e.g. electrical/chemical
Castrated Criminals Can’t Really Sex
Name three types of lipid in a membrane?
Phospholipids
Glycolipids
Cholesterol
What are the main components of a phospholipid?
Polar head group Attached to.. Phosphate Attached to.. Glycerol backbone Attached to.. Fatty acid chains
What are the main types of polar head groups?
Choline, amines, amino acids, sugars
What are the main types of fatty acid chains?
Hydrophobic
Can be saturated or unsaturated which contain cis C=C. Introduces a ‘kink’ to the fatty acid tail.
Why is sphingomyelin different to most Phospholipids?
Has no glycerol backbone but is still classed as a phospholipid as it has a phosphate. Contains sphingosine.
What is an ampipathic molecule?
contain both hydrophilic (the “head”) and hydrophobic (the “tail”) regions.
Where are unsaturated fatty acids found? Give an example
In the diet
Linolenic acid
What Sphingoyelin found? What is its function?
In myelin sheathes, aids in signal transduction
What is a glycolipid?
lipids with a carbohydrate group attached
Give the structure of a glycolipid
Sugar head group (Cerebroside or Gangioside)
Sphingosine backbone
Nitrogenous base
Fatty acid tail
Cerebroside?
monomer head group e.g. galactose
Ganglioside?
oligosaccharide head group
What is cholesterol derived from?
HMG-CoA
What is the enzyme used to convert precursor to cholesterol? What drug inhibits this enzyme?
HMG-CoA reductase
Statins
Give the structure of cholesterol
Polar head –OH which is attracted to exposed C=O in phospholipids’ fatty acid tails
Rigid, planar steroid ring
Non-polar hydrophobic carbon tail
What two things will an ampipathic molecule form in water?
A micelle or a bi-layer
Describe formation of a lipid bi-layer
Spontaneous
Driven by van der waals attractive forces between the hydrophobic tails
Electrostatic and hydrogen bonding between hydrophilic moieties; and interactions between hydrophillic groups and water stabilise the bilayer.
What do unsaturated phospholipids do in a bilayer?
unsaturated phospholipids will reduce packing (due to the kink in the tail), so increasing its fluidity
What are pure lipid bilayers impermeable to?
ions and most polar molecules, allowing only small, uncharged molecules to pass through
What are the four modes of mobility of lipid bilayers?
1) Intra Chain motion (kink formation in fatty acyl chains)
2) Fast axial rotation (Phospholipid rotates)
3) Fast lateral diffusion (Phospholipid displace each other laterally)
4) Flip-flop movement of lipid molecules from one half of the bilayer to the other. This is least likely to happen due to the energies involved, which need to be high to achieve this.
How can cholesterol stabilise phospholipid bilayers?
- In high temperatures, they can form H+ bonds with other phospholipids, reducing the chain motion of membrane lipids, reducing fluidity
- In low temperatures, they reduce phospholipids packing by just breaking up the phospholipids, breaking any bonds they form with one another, increasing fluidity.
Intercalation of the rigid planar conjugated ring structure reduces phospholipid packing and therefore increases fluidity.
Conversely, the rigid conjugated ring structure reduces phospholipid aliphatic tail mobility, so reducing fluidity.
What does cholesterol stabilisation of lipid bilayers mean?
Maintain homegenous environment regardless of temperature
What is an integral lipid protein, and what forces associate them with the membrane?
Embedded in the bilayer
Interact with the hydrophobic regions of the bilayer
How can intergral proteins be removed?
by agents which compete for the non-polar interactions in the bilayer e.g. detergents/ organic solvents
What is a peripheral protein associated with? How is it bound?
Associated with the surface
Bound to membrane surface by electrostatic and H-bond interactions
How can a peripheral protein be removed?
By pH or ionic strength changes
What is an erythrocyte (rbc) cytoskeleton made up of?
a network of spectrin and actin molecules attached to the membrane through adapter proteins.
What does attachment of integral membrane proteins to cytoskeleton do in erythrocytes?
restricts the lateral mobility of the membrane protein
What is erythrocyte cytoskeleton important?
important structure in maintaining the deformability necessary for the erythrocytes to make their passage through capillaries without lysis
What is hereditary spherocytosis?
Spectrin levels depleted by 40-50% in erythrocytes
Cells much less resistant to lysis and become sphere-shaped
What happens to erythrocytes in hereditary spherocytosis?
Cleared by the spleen as wrong shape > spleenomegaly > haemolysis is extravascular.
Leads to haemolytic anaemia due to shortened in vivo survival and inability of bone marrow to compensate for their reduced lifespan.
What is hereditary elliptocytosis?
Spectrin molecules unable to form heterotetrameres (spectrin structure) resulting in fragile elliptoid cells
Alters deform-ability of erythrocyte
Where do the N terminus and C terminus go in integral proteins
N-terminus outside membrane of ER, C-terminus inside cell cytoplasm
Describe process of insertion into ER of integral protein
- SRP binds to signal sequence of growing polypeptide at ribosome
- Guides ribosome and polypeptide to SRP receptor
- SRP released
- Signal sequence at the N-terminus interacts with a signal sequence receptor within a protein translocator complex in the ER membrane
- For membrane proteins the passage of the protein through the cell membrane must be stopped.
- A stop transfer signal i.e. a highly hydrophobic primary sequence followed by charged amino acids in a-helical form which is long enough to span the hydrophobic core of the bilayer. This sequence forms the transmembranous region of the protein.
- Result: transmembrane protein with it’s N-terminal directed into the ER lumen and it’s C-terminal into the cytoplasm of the cell
What happens to membrane protein after ER processing?
Undergoes further processing as it passes from the ER to the cis/trans golgi . Vesicle will then fuse with the plasma membrane.
What is a multiple membrane domain?
Folding of the nascent protein against the constraint of the first transmembrane segment is the driving force for the insertion of other domains.
What is membrane asymmetry?
Asymmetrical orientation of proteins in biological membranes is important for function e.g. a receptor must have its recognition site directed towards the extracellular space.
What do C=C in fatty acids chains do?
disrupt the hexagonal packing of phospholipids increase membrane fluidity.
What do membrane proteins do?
Embedded in bilayer and carry out distinctive functions e.g. enzymes, transporters, pumps, ion channels, receptors and energy transducers
Give three ways proteins in lipid bilayers can move
- Conformational change
- Rotation
- Lateral diffusion
Give one way proteins in lipid bilayer cannot move and why
1.NO FLIP-FLOP as they are large and could disrupt the amphipathic nature of the membrane
What is protein mobility restrained by? (3)
Lipid mediated effects – proteins tend to separate out into the fluid phase or cholesterol poor regions
Membrane protein associations
Association with extra membranous proteins e.g. cytoskeleton (peripheral proteins)
