Lipids and cell membranes Flashcards
What are the 6 steps of cell to cell communication?
- Synthesis of signal
- Release of the signalling molecule by the signalling cell
- Transport of the signal to the target
- 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
What are the 2 long range transport of signal methods?
- Endocrine
* Neurotransmission
What is endocrine transport?
The hormone is released by an endocrine cell and is carried in the bloodstream to distal target cells
What is an example of endocrine transport?
Follicle stimulating hormone released form the pituitary acts upon the ovary
Give an example of neurotransmission
Breathing- the phrenic. and thoracic nerves send impulses from the brain to the diaphragm
What is paracrine signalling?
Signalling molecules that 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 a type of paracrine signalling)
What is autocrine signalling?
Cells respond to substance that they themselves release
Give an example of autocrine signalling
Some neurotransmitters and growth factors bind to the cells that release them (lets cells know that enough has been released)
What are the short range signalling methods
- Paracrine signalling
- Autocrine signalling
- Membrane bound proteins that intact to signal (T cells)
Give an example of a type of cell in which multiple types of signalling can be occurring simultaneously and describe how
- Insulin release from pancreatic beta cells
- Autocrine
- Paracrine to alpha cells
- Endocrine: insulin enters the blood stream where it travels to the liver /muscle/ Adipose Tissue
What are the 4 types of receptor?
- Ligand gated ion channels (ionotropic receptor)
- G-protein-coupled receptors (metabotropic)
- Kinase-linked receptor
- Nuclear receptor
Describe the ligand gated ion channel receptor including time frame and an example
Binding opens an ion channel which leads to hyper polarisation or depolarisation of the cell
• Milliseconds
• Nicotinic acetylcholine receptor
Describe the G-protein-coupled receptors including time frame and an example
Binding activates a G protein which then goes on to either:
• Open a ion channel, causing the cell to become hyper polarised or depolarised
• Activate a second messenger pathway causing calcium release, protein phosphorylation or something else which causes a cellular effect
• Seconds
• Muscarinic Acetylcholine receptor
Describe the Kinase-linked receptor including time frame and an example
- Binding causes protein phosphorylation which causes gene transcription then protein synthesis
- Hours
- Cytokine receptors
Describe the nuclear receptor including time frame and an example
- Signalling molecule enters the cell and then the nucleus where it binds to the receptor
- Binding in the nucleus causes gene transcription and then protein synthesis
- Hours
- Oestrogen receptor
What are eicosanoids?
They are inflammatory mediators known as local hormones
• They have specific effects on target cells close to their site of formation
• They are rapidly degraded(not transported to the distal sites within the body
• Main source is arachidonic acid
What are the principle eicosanoids?
- Prostaglandins
- Thromboxanes
- Leukotrienes
Describe the structure of arachidonic acid
- 20 carbon unsaturated fatty acid
* contains 4 double bonds
What is the effect of prostaglandins?
- Dependent on the receptor: EP1=vasoconstriction, EP2= vasodilation
- Involved in the inflammatory response, thermoregulation (fever) and pain
Where are prostaglandins synthesised?
In all tissues and cell types
What is Phophatidylinositol?
- Phosphatidylinositol 4,5-bisphosphate (PIP2) is a phospholipid in the lipid bilayer
- It is the substrate of phospholipase C (PLC)
- PLC liberates 2 signalling molecules from PIP2: Inositol 1,4,5 trisphosphate (IP3) and diacyglycerol (DAG)
Describe the Inositol phospholipid signalling pathway
- Signalling molecule binds to a G protein linked receptor
- G protein alpha subunit is activated and activate phospholipase C (PLC)
- Phospolipase liberates 2 signalling molecules from PIP2: Inositol 1,4,5 trisphosphate (IP3) and diacyglycerol (DAG)
- The IP3 causes Ca2+ channels in the endoplasmic reticulum to open
- PKC is activated
Give 3 substrates for PKCs
- Tumour supressor p53 which prevents tumour formation
- Ca v 1.2 (a calcium channel) which causes heart contraction
- IKKα (cytokine) which activates B cells
What happens to IP3 after signal transduction has taken place?
IP3 is recycled back to the membrane as PIP2
What are thromboxanes?
- Synthesised in platelets
- Short lived (autocrine/paracrine)
- Thromboxane A2 (TXA2) has prothrombotic properties
- Stimulate platelet aggregation
- Vasoconstrictor
What are leukotrienes?
- Synthesised in white blood cells (Leuko)
- Contain a triene system of double bonds
- Some contain cysteine
- Involved in the immune response
- Heavily implicated in asthma and allergy
What is involved in vasoconstriction?
- Thomboxanes
- Prostaglandins (EP1 receptor)
- Platelet activating factor
What is involved in vasodilation?
• Prostaglandins (EP2 receptor)
What stimulates platelet aggregation?
- Thromboxane
- Platelet activating factor
- Prostaglandins can both inhibit and promote it
What is involved in inflammation?
- Platelet activating factor
* Prostaglandins
What is involved in the immune response?
- Leukotrienes
* Platelet activating factor
What are NSAIDs?
- Non steroidal anti-inflammatory drugs
* e.g. Aspirin and Ibuprofen
What is the affect of NSAIDs?
- Inhibit the formation of prostaglandins involved in fever, pain and inflammation
- Inhibit blood clotting by blocking thromboxane formation in blood platelets
What is the mechanism of action of ibuprofen?
• Block the hydrophobic channel by which arachidonate enters the cyclooxygenase active site
What is the mechanism of action of aspirin?
- Inhibits thromboxane formation via COX-1 inhibition in blood platelets
- Acetylates a serine hydroxyl group near the active site, preventing arachidonate from binding
- Aspirin binds irreversibly
why are the effects of aspirin long lived?
Because platelets lack a nucleus and don’t make new enzymes
How is arachidonic acid formed?
From Phospholipids via chemical and mechanical stimuli which activate PLA2
How can Arachidonic acid be metabolised?
a) By cyclo-oxygenase and peroxidase
• Produces endoperoxidases
b) By lipoxygenases to give leukotrienes
What is formed from Endoperoxidases?
- Prostaglandins
- Prostacyclin
- Thromboxane A2
How is Platelet Activating factor formed?
From Phospholipids (PLA2 enzyme)
How are prostaglandins formed?
- Phospholipid –> Arachidonic acid (PLA2)
- Arachidonic acid –> Endoperoxidases (Cyclooxygenase)
- Endoperoxidases –> Prostaglandins
What are some examples of lipid soluble molecules?
- Cortisol
- Estradiol
- Testosterone
- Thyroxine
Describe the mechanism of action of cortisol
- Passes into the cell
- Binds to an intracellular receptor protein which becomes activated
- The activated receptor-cortisol complex moves into the nucleus
- The complex binds to the regulatory region of the target gene and activates transcription
Describe the formation of eicosanoids
- Phospholipids to arachidonic acid and platelet activating factor (PAF) by action of Phospholipase A2 (PLA2)
- Arachidonic acid to endoperoxidases by action of cyclooxygenases and peroxidase
- Arachidonic acid to hydroperoxy and hydroxy fatty acids by action of lipoxygenase
- Endoperoxidases to prostaglandins, prostacyclin and thromboxane A2
- Hydroperoxy and hydroxy fatty acids to leukotrienes
