What is the composition of phospholipids?
Glycerol bound to fatty acid chains (ester bonds) and to a head group by a phosphate molecule
Head group determines type of phospholipid e.g. choline, inositol, amines, sugar
note: cis double bond in fatty acid chain introduces kink - reduces phospholipid packing
List some general and specific functions of biological membranes.
GENERAL:
- continuous, highly selective permeable barrier
- control of enclosed chemical environment
- communication
- recognition of signalling molecules, adhesion proteins, and immune surveillance
- signal generation in response to stimuli
SPECIFIC:
- interaction with adjacent cells
- absorption & secretion
- changing shape for transport
- synapses: electrical signal conduction
What is the composition of sphingomyelin?
Phosphocholine bound to fatty acid (but NO GLYCEROL)
Often found in myelin sheaths
What is the composition of a glycolipid, and what two types are there?
Replace sphingomyelin phosphocholine with sugar
CEREBROSIDE = sugar monomer head group
GANGLIOSIDE = oligosaccharide head group
Describe the range of motion of phospholipids.
LATERAL DIFFUSION
ROTATION
FLEXION (vibration)
FLIP-FLOP (rare - high energy conformation needed)
Describe how cholesterol affects phospholipid packing.
OH forms hydrogen bonds with fatty acids -> reduced phospholipid chain motion -> reduced fluidity
Forces phospholipid molecules further apart -> reduces phospholipid packing -> increased fluidity
How does cholesterol make membranes more stable?
Eliminates endothermic phase transition of phospholipid bilayers, therefore less energy required to be fluid.
note: formation of crystalline islands -> fractures -> leakage
Describe the range of motion of proteins in phospholipid bilayers.
LATERAL DIFFUSION
CONFORMATIONAL CHANGE
ROTATION
note: NO FLIP-FLOP (proteins too large/hydrophobic)
What is the evidence that there are proteins in membranes (generally)?
Functional:
- facilitated diffusion
- ion gradients
- specificity of cell responses
Biochemical:
- membrane fractionation
- freeze fracture
How is the movement of membrane proteins restricted?
Aggregation of adjacent membrane proteins
Tethering of membrane proteins (intracellularly or extracellularly)
Interaction with membrane proteins of other cells
How fluid the surrounding lipid parts of the membrane are
What is the functional difference between integral and peripheral membrane proteins, and how can they each be separated from the membrane?
INTEGRAL:
Interact with hydrophobic domains of lipid bilayer.
Only removed with agents that compete for these interactions e.g. detergents, organic solvents
PERIPHERAL:
Form electrostatic interactions/hydrogen bonds with phosphate heads
Removed by changes in pH/ionic strength
Describe the components of the cytoskeleton.
Spectrin (alpha and beta subunits in antiparallel arrangement)
Ankyrin between membrane proteins and spectrin
Actin cross links & adducin present
Band 3, glycophorin (band 7) in membrane; band 4.1 by actin
What two disorders can result from reduction/defect of spectrin?
Hereditary spherocytosis:
- spectrin depleted by ~40%-50%
- erythrocytes round up
- less resistant to lysis - cleared by spleen (anaemia)
Hereditary elliptocytosis:
- defect in spectrin molecule - unable to form heterotetramers
- fragile elliptoid cells
How might a membrane protein interact with the hydrophobic domain of the membrane bilayer?
- transmembrane sequence: ~20-22aa with hydrophobic R regions
- lipid-linked proteins: insertion of hydrophobic lipid moieties e.g. palmitoylation, mystriolation
- insertion of amphipathic alpha-helix from cytoplasmic side
