Lipids in Cell Membranes (2) Flashcards
State the function of phospholipids
Participate in cell-cell communication mechanisms by giving rise to intracellular second messengers.
Serve as precursors for compounds that are released from cells and act on other cell types, called eicosanoids.
Describe the steps in cell-cell communication
Synthesis of signal
Release of signalling molecule by the signalling cell (via diffusion, exocytosis, cell-cell contact)
Transport of signal to the target cell
Detection of the signal by a specific receptor protein.
A change in cellular metabolism, function or development triggered by the receptor-signal complex.
Removal of the signal OR desensitisation.
Describe signal transduction
Detection of the signal by a specific receptor protein.
A change in cellular metabolism, function or development triggered by the receptor-signal complex.
Describe transport of signals
Signals can be short or long range.
In animals, signalling by extracellular molecules can be classified into different types.
State the 2 types of long-range signalling
Endocrine signalling
Neurotransmission
Describe endocrine signalling
Hormone released by endocrine cell and carried in bloodstream to distal target cells.
Give an example of endocrine signalling
FSH released from the pituitary acts upon the ovary.
What type of signalling is endocrine signalling ?
Long range
Describe neurotransmission
This is where a signal is passed along a network of neurons, through a series of neurotransmitter release receptor activation events.
Give an example of neurotransmission
Breathing
The phrenic and thoracic nerves send impulses from the brain to the diaphragm.
State some short-range signalling types
Paracrine
Autocrine
Membrane bound proteins can interact to signal
Describe paracrine signalling
Signalling molecules only affect target cells in close proximity to secreting cells.
Give an example of paracrine signalling
Somatostatin release by pancreas cells acts locally.
Neurotransmission can also be considered to be a type of paracrine signalling.
Describe autocrine signalling
Cells respond to substances that they themselves release.
Give an example of autocrine signalling
Some neurotransmitters and growth factors bind to the cells that release them.
Describe how membrane bound proteins can interact to signal
This is where you have a signalling molecule expressed on the cell surface and it binds to a receptor on an adjacent target cell.
Give an example in which membrane bound proteins interact to signal
Signalling by T cells in the immune system
Give an example of where multiple types of signalling can be occurring simultaneously
Insulin released from pancreatic B cells acts in an autocrine, a paracrine and an endocrine manner.
How do signalling molecules act ?
Act on membrane bound receptors that control the production of intracellular chemicals (second messengers)
DO NOT ENTER CELLS
State the function of ‘second messengers’
Mediate cell activity
State the exception to how most signal molecules act
Lipid soluble signalling molecules
- they bind intracellular receptors
Describe how signalling molecules bind to cell-surface receptors (extracellular receptors)
Extracellular receptors which are on the cell surface, bind to a hydrophilic signalling molecule.
Describe how signalling molecules bind to intracellular receptors
Intracellular receptors (often reside in the nucleus)
Signalling molecules are hydrophobic and so can pass through the membrane, to get to the nucleus where they bind to the receptor.
Function of intracellular receptors
Usually involved in the switching on/off of genes and making new proteins.
State the 4 types of receptors
Ligand gated ion channels
(Ionotropic)
G protein coupled receptors
(Metabotropic)
Kinase-linked receptors
Nuclear receptors
State some examples of Ligand gated ion channels
(Ionotropic) receptors
Nicotinic
ACh receptor
(ms)
State some examples of G protein coupled receptors
(Metabotropic)
Muscarinic
ACh receptor
(s)
State some examples of Kinase-linked receptors
Cytokine receptor
(hours)
State some examples of Nuclear receptors
Oestrogen receptor
(hours)
Describe what happens when an extracellular signalling molecule binds to a cell-surface receptor
- Switching on of genes (altered protein synthesis)
- Proteins already in the cell with an altered function
Both processes give rise to alteration in cytoplasmic machinery in the cell and a change in cel behaviour.
State some lipid soluble molecules
Steroid hormones (lipids)
Describe the action of lipid soluble molecules
Pass through the cell membrane
Combine to a receptor within the nucleus
Switch on transcription of genes
Results in protein synthesis and an altered functional response.
Describe the action of cortisol
Cortisol binds to a receptor in the cytoplasm
When it recognises its receptor, it is translocated to the nucleus and it switches on gene transcription.
State the phospholipid that resides in the cell membrane and is present in significant amounts
Phosphatidylinositol 4,5 bisphosphate
(PIP2)
Where is Phosphatidylinositol 4,5 bisphosphate (PIP2) found ?
Found in the lipid bilayer
What is Phosphatidylinositol 4,5 bisphosphate (PIP2) ?
It is the substrate of the enzyme phospholipase C (PLC)
Function of phospholipase C
Liberates 2 signalling molecules from PIP2
- IP3
- DAG
(these molecules are second messengers)
Function of Calcium
Activates cellular pathways
Ca2+ conc increases in the cell in response to IP3 release.
Calcium binds to proteins to regulate their function
State some substrates for PKC’s
Tumour suppressor p53 (transcription factor)
Cav 1.2 (calcium channel)
IKK alpha (cytokine)
Function of Tumour suppressor p53 (transcription factor)
Prevents tumour formation
Function of Cav 1.2 (calcium channel)
Heart muscle contraction
Function of IKK alpha (cytokine)
B cell activation
- Immune function
What are eicosanoids ?
Inflammatory mediators
(local hormones)
Where are eicosanoids derived from ?
Phospholipid derived
Why are eicosanoids considered as ‘local hormones’ ?
They have specific effects on target cells close to their site of formation. (autocrine/paracrine)
They are rapidly degraded, so are not transported to distal sites within the body.
State some features of eicosanoids
Unstable
Don’t last very long
Name the 3 main types of eicosanoids
Prostaglandins
Thromboxanes
Leukotrienes
Eicosanoid meaning
‘Eicosa’ - 20 carbon atoms
‘Enoic’ - Double bonds
What is the main source of eicosanoids ?
Arachidonic acid
State some features of arachidonic acid
A 20 Carbon, unsaturated fatty acid, containing 4 double bonds.
(20:4)
What is the initial and rate limiting step in eicosanoid synthesis ?
Liberation of arachidonic acid by phospholipase A2 (PLA2)
How is PLA2 activated ?
By a variety of receptor mediated signals
State some ways in which PLA2 is activated
Serotonin receptors
Glutamate receptor 1
Some cytokine receptors
Increase in intracellular calcium levels
Describe eicosanoid biosynthesis
Through the action of PLA2, phospholipids can be converted into arachidonic acid.
[By-product of platelet-activating factor]
The arachidonic acid can then be processed by 2 different classes of enzymes.
State how arachidonic acid can be metabolised
BY 2 classes of enzymes :
- Cyclo-oxygenase
- Lipooxygenases
State the function of cyclo-oxygenases
Cyclo-oxygenases (and peroxidase) metabolise arachidonic acid to give prostaglandins and thromboxanes.
State the function of Lipoxygenases
Lipoxygenases metabolise arachidonic acid to give leukotrienes.
Where are prostaglandins synthesised ?
Synthesised in all tissues and cell types
Function of prostaglandins
Inducing vasoconstriction/ vasodilation
Gives rise to redness, swelling and heat
Inhibits/promotes platelet aggregation.
What does the effects of prostaglandins depend on ?
Depends upon receptor
Function of EP1 receptor
Vasoconstriction
Function of EP2 receptor
Vasodilation
Key functions of prostaglandins
Inflammatory response
Thermoregulation (Fever)
Pain
Where are thromboxanes synthesised ?
Synthesised in platelets (clotting)
Describe some features of thromboxanes
Short lived (autocrine/paracrine)
Function of thromboxanes
Stimulates platelet aggregation
Vasoconstrictor
State the function of leukotrienes
Immune response
Heavily implicated in asthma and allergy
Describe the structure of leukotrienes
Contains a conjugated triene system of double bonds
Some contain amino acid cysteine in their structure
What is the function of cysteine in leukotrienes ?
Anaphylactic shock
Where are PAF synthesised ?
By-product of arachidonic acid liberation
Synthesised in leukotrienes.
Also synthesised by injured tissue.
Function of PAF
Stimulates platelet aggregation
Vasoconstriction
Inflammation
Immune response (also anaphylaxis)
What are NSAID’s ?
Non-steroidal anti-inflammatory drugs
State the function of NSAIDs
Inhibit :
- Formation of prostaglandins involved in fever, pain and inflammation
- Blood clotting by blocking thromboxane formation in blood platelets
Name some NSAID’s
Aspirin
Derivatives of ibuprofen
Describe the action of ibuprofen
Block the hydrophobic channel by which arachidonate enters the cyclooxyrgenase active site.
Describe the action of aspirin
Aspirin acetylates a serine hydroxyl group near the active site, preventing arachidonate binding.
What types of inhibitors are aspirin and ibuprofen ?
Aspirin : Irreversible inhibitor
Ibuprofen : Reversible inhibitor
Why is the action of aspirin long lived in platelets ?
Platelets lack a nucleus and so do not make new enzyme.
Cox1 inhibited, stays inhibited
Function of aspirin
Anti-clotting effect
Inhibition of thromboxane formation (via Cox1 inhibition) in blood platelets
