Membranes Flashcards
4 kinds of membrane proteins?
Receptors
Ion channels
Adhesion molecules
Transporters
What do ion channels do?
Mediate electrical signalling between cells
4 types of receptors
Ligand-gated ion channels
G-protein-coupled receptors
Kinase-linked receptors
Nuclear receptors
What kind of receptor does glucagon activate?
G-protein coupled receptors
What kind of receptor does insulin activate?
Receptor tyrosine kinases
Example of intracellular receptor
Nuclear receptor
What receptors do many drugs utilise?
G-protein coupled receptors
What does the alpha subunit stimulate when the G-protein coupled receptor is stimulated?
AC- adenelaine cyclase
What secondary messenger does AC produce?
Cyclic AMP
Example of what activates G-protein coupled receptors?
Glucagon
Adrenalin
Example of what activates steroid hormone receptors
Sex hormones
Cortisol
Are the responses to steroid hormone receptors faster or slower than G-protein coupled receptors?
Slower, because they are activating gene expression which can take days
G-protein receptors act immediately, very quick
What has a role in metastasis of cancer?
Integrins
Some common functions of membranes (6)
Define boundaries of cell
Allow import and export
Retain metabolites and ions within the cell
Sense external signals and transmit information into the cell
Nerve signals
Store energy (proton gradient)
What is the main structure formed of?
Lipid bilayer
What stabilises membranes?
Noncovalent forces, especially hydrophobic effect and van der waals
What are membrane lipids?
Small amphipathic molecule that form closed biomolecular sheets
Are the inner and outer surfaces of membranes the same?
No they differ which gives asymmetry
What does the closed bimolecular sheet that membranes form prevent?
The movement of polar or charged molecules
What do membrane proteins mitigate?
The impermeability of membranes
Allow movement of molecules and information
Are membranes covalent or non covalent assemblies?
Noncovalent
3 major structures observed when lipids aggregate into structures in water
Michelle’s
Bilayers
Liposomes
What does the which structure is formed when lipids aggregate depend on?
Type of lipid
Concentration
What are micelles?
Spherical structure containing amphipathic molecules arranged with hydrophobic regions in the interior
When is the micelles lipid structure favoured?
When the cross sectional area of the head of the group is greater than that of the acyl side chains
When is the bilayer lipid structure favoured?
When the cross sectional area of the head of the group and the acyl side chains are similar
When does the liposome (vesicle) lipid structure form?
When the bilayer folds on itself to form a hollow sphere
Different name for liposomes
Lipid vesicles
Which part of lipids are hydrophobic?
Fatty acid tail
What kind of movement does the fluid mosaic model allow for?
Lateral movement
Does the fluid mosaic model allow for rotation through the membrane?
No
2 types of lipid movement in membranes
Lateral diffusion
Transverse diffusion (flip-flop)
Which lipid movement in membranes is rapid?
Lateral diffusion
Which lipid movement in membranes is very slow?
Transverse diffusion
What disrupts the tight packing of the fatty acid chains?
Cholesterol
5 physical properties of membranes
Dynamic and flexible structures
Can exist in various phases and undergo phase transitions
Not permeabe to large polar solutes and ions
Permeable to small polar solutes and non polar compounds
Permeability can be artificially increased by chemical treatment
2 liquid phases of the membrane
Liquid-ordered state (gel phase)
Liquid-disordered state (fluid phase)
Do individual molecules move around in the liquid-ordered state?
No
Do individual molecules move around in the liquid-disordered state?
Yes
What causes phase transition from gel to fluid?
Heating
What are membranes more like under physiological conditions, fluid-like or gel-like?
Fluid-like
What do more fluid membranes require?
Shorter and more unsaturated fatty acids
What happens to the melting point when double bonds are added to the fatty acids?
It decreases
How does the length of saturated fatty acids affect the melting temperature?
Increased length increases the melting point
Why are transverse diffusions rare?
Because the charged head group must transverse the hydrophobic tail region of the membrane
Which enzymes catalyse transverse diffusion?
Flippase
Floppies
Scramblase
What does the enzymes that catalyse transverse diffusion use to move the lipids against the concentration gradient?
ATP
What does the lipid composition of membranes vary by?
Organisms
Tissues
Organelles
What does the unique lipid composition of each membrane type reflect?
The functional specialisation
What does membrane fluidity depend on?
Temperature
Lipid composition
What does the melting temperature depend on?
Length of fatty acids
Degree of cis unsaturation
What does lipid rafts contain?
Clusters of glycosphingolipids with longer-than-usual tails
Specific doubly or triply acylated proteins
Are lipid rafts more or less ordered?
More
What does lipids rafts allow segregation of?
Proteins in the membrane
What clusters together in membrane rafts?
Sphingolipids and cholesterol
What do lipid rafts do?
Help to moderate membrane fluidity
Function in signal transduction
What does the eukaryotic plasma membrane consist of?
Phospholipidbilayer with proteins and cholesterol embedded
Where do tyr and trp cluster in membranes?
At the non polar/polar intereface
What doe beta strands form in the membrane?
A pore
What signals do receptor proteins receive?
Light
Hormones
Neurotransmitters
Phereomones
What passes through channel, gate and pump proteins?
Nutrients
Ions
Neurotransmitters
When can integral membrane proteins be removed from the membrane?
In the presence of strong detergents
When are peripheral (non-GPI linked) membrane proteins dissociated from the membrane?
During changes in ionic strength (pH changes)
When are ampitrophic and GPI-linked proteins linked to the membrane?
During specific regulatory events
What do peripheral membrane proteins associate with?
The polar head groups of membranes
How are peripheral membrane proteins associated with the membrane?
Through ionic interactions with the lipids
or
Aqueous domains of integral membrane proteins
How are peripheral membrane proteins removed?
Disrupting ionic interactions with either high salt or change in pH
How can amphitropic proteins be conditionally attached to the membrane?
By covalent interaction with lipids or carbohydrates attached to lipids
What is farnesylation
A type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added to a cysteine residue
Where can proteins be targeted by farnesylation?
The inner leaflet of the plasma membrane
What can farnesylation be an intermediate in?
The lipidation of proteins
What catalyses the farnesylation reaction?
Farnesyl transferase
3 general types of membrane lipids
Phospholipids
Glycoplipids
Sterols
Which is the major class of membrane lipids?
Phospholipids
4 components of phospholipids
2 fatty acid tails
A platform
A phosphate
An alcohol
2 common phospholipid platforms
Glycerol
Sphingosine
Which kind of phosphilipds are the primary constituents of cell membranes?
Glycerophospholipids
What kind of linkage do the fatty acids form with the first and second hydro groups?
Ester linkage
Is the phosphate group of glycerophospholipids charged or not at physiological pH?
Charged
What are glycerophospholipids named as?
Derivatives of phosphatidic acid
What kind of fatty acids are in glycerophospholipids?
Both saturated and unsaturated
Which is the major component of most eukaryotic cell membranes?
Phosphatidylcholine
What is the backbone of sphingolipids?
A long chain amino alcohol sphingosine
What kind of linkage is the fatty acid in sphingolipids joined to sphingosine via?
Amide linkage
What is a polar head group connected to sphingosine by in sphingolipids?
Glycosidic or phosphodiester linkage
What is sphingomyelin?
A common membrane lipid in which the primary hydroxyl group of sphingosine is esterfied to phosphorylcholine
Where are sphingomyelin abundant?
In myelin sheath that surrounds some nerve cells
What is sphingomyelin st5ructually similar to?
Phosphatidycholine
What do membrane sphingolipids serve as?
Sources of intracellular messengers
What are ceramide and sphingomyelin potent regulators of?
Protein kinases
What is ceramide involved in th regulation of?
Cell division
Differentiation
Migration
Programmed cell death
Can membrane lipids include carbohydrate moieties?
Yes
What are glycolipids derived from?
Sphingosine
Which are the simplest glycolipids (only containing a single sugar) ?
Cerebrosides
How many sugar molecules can gangliosides contain?
7
What do gangliosides have as their pola head groups?
Oligosaccharides
Where are gangliosides present?
In the grey matter of the human brain
Example of a cell type with relatively low membrane protein content
Schwann cell
Example of a demyelination disease, impairing myelin assembly or damaging existing myelin
Multiple sclerosis
What, in part, determines the blood groups?
Type of sugars located on the head groups in glycosphingolipids
What is the structure of sugar determined by?
An expression of specific glycosyltransferases
What removes one of the 2 fatty acids in lipids?
Phospholipases of the A type
Which removes the other of the 2 fatty acids in lipids?
Lysophospholipases
Where are structural lipids degraded?
In the lysosome
What are phospholipids degraded by?
Phospholipases A-D
What are gangliosides degraded via?
A series of enzymatic cleavages
What does a failure to correctly degrade gangliosides result in?
Build-up of lipids in lysosomes
Dysfunction called lysosomal storage disorder
What is the lysosome known as?
The cell’s recycling center
What does an accumulation of gangliosides contribute to?
Neurodegeneration
What is cholesterol?
A lipid based on a steroid nucleus
A steroid
What is cholesterol modified by?
On one end: attachement of fatty acid chain
On the other end: hydroxyl group
What does the hydroxyl group of cholesterol interact with in membranes?
Phospholipid head groups
What is a sterol made up of?
Steroid nucleus: 4 fused rings
Hydroxyl group (polar head) in the A-ring
Various non polar side chains
How many fused rings do sterols have?
4
Are sterols planar?
Relatively
What do steroid hormones regulate?
Gene expression
What are bile acids?
Polar derivatives of cholesterol
What do bile acids emulsify?
Dietary fats on the intestine
How do mammals obtain cholesterol?
From food
Synthesise it de novo in the liver
Via what is cholesterol bound to proteins transported to tissues?
Blood vessels
What are steroids?
Oxidized derivatives of sterols
How do sterol differ from cholesterol?
They lack the alkyl chain
Are steroids more or less polar than cholesterol?
More
Where ar3e steroid hormones synthesized?
Gonads
Adrenal glands
What are ether lipids?
lipids where one of the two acyl chains are attached to glycerol in ether linkage instead of ester
What are platelets-activating factor?
Aliphatic ether analog of phosphatidylcholine
What do platelet-activating factor stimulate?
The aggregation of blood platelets
2 types of passive transport across the membrane
Simple diffusion
Facilitated diffusion
2 types of cell surface receptors
Ligan gated ion channels
G-protein coupled receptors
4 types of ligand activated receptors
Ligand-gated channels
Ligand binding receptor-enzyme
G protein-coupled receptor
Intergrin
What mediates signal transduction for cellular response to extracellular stimuli?
Receptors
Which receptor is very commonly used by drugs?
G-protein coupled receptors
Which nucleotides do G protein-coupled receptors bind?
Guanine nucleotides GDP and GTP
What subunits do G protein-coupled receptors have?
Heterotrimeric Alpha, beta and gamma subunits
What alters G protein-coupled receptors?
GPCR’s binding of ligand
Which is the largest family of integral membran proteins?
G protein-coupled receptors
What is GPCR short for?
G protein-coupled receptors
What do steroid hormone receptor activate?
Long term responses
2 main functions of integral receptors
Attachment of the cells to the ECM
Signal transduction from ECM to cells
What subunits are integrins composed of?
Alpha
Beta
What kind of dimers are integrins?
Heterodimers
What does, in large part, defines the metabolic activities of a given cell type?
The expression of transporters
What does the nature of the membrane transporters dictate?
The biochemical processes that occur inside the cell
What are molecules if they are lipophilic?
Hydrophobic
Do lipophilic molecules require the assistance of proteins to cross the membrane?
No, they cross via simple diffusion
Which molecules require a channel (facilitated diffusion and passive transport) to move across the membrane?
Polar
Fully charged molecules
What allows for rapid movement of ions across membranes down their concentration gradient?
Ion channels
