Lipids in cell membranes 2 Flashcards
What are the roles of phospholipids?
They participate in cell-cell communication mechanisms by giving rise to intracellular second messengers They also serve as precursors for compounds that are released from cells and act in other cell types called Eicosanoids
What are Eicosanoids?
Inflammatory mediators
What are the 6 steps involved in cell-cell communication?
- Synthesis of signal 2. Release of the signaling molecule by the signaling cell: exocytosis, diffusion, cell-cell contact 3. Transport of the signal to the target cell 4. Detection of the signal by a specific receptor protein 5. A change in cellular metabolism, function or development triggered by the receptor-signal complex 6. Removal of the signal or desensitisation
What are the 2 ranges signals can be ?
Short or long-range
What are the 2 different types of long range cell to cell communication?
1). Endocrine: hormone released by endocrine celll and carried in the bloodstream to distal target cells E.g - FSH released from pituitary acts upon the ovary 2). Neurotransmission E.g - Breathing - the phrenic and thoracic nerves send impulses from the brain to the diaphragm
What are the 3 different types of short range cell to cell communication?
1). Paracrine: signalling molecules only affect target cells in close proximity to secreting cells E.g - Somatostatin release by pancreas cells acts locally. Neurotransmission can also be considered to be a type of paracrine signalling 2). Autocrine: Cells respond to substances that they themselves release E.g - Some neurotransmitters and growth factors bind to cells that release them (like negative feedback) 3). Membrane-bound proteins: Can interact to signal by the plasma membrane attached proteins E.g - Signalling by T cells in the immune system
How do all of the different types of signalling interact with one another?
Multiple types of signalling can be occurring simultaneously E.g - Insulin released from pancreatic B-cells acts in an autocrine, a paracrine and endocrine manner
How do the majority of signalling molecules that affect cell activity or function work on the cell?
They do not enter the cells and act on membrane bound receptors that control the production of intracellular chemicals (second messengers) - Usually hydrophilic These mediate cell activity The exception is lipid soluble signalling molecules, they bind to intracellular receptors (usually hydrophobic)
How do Ligand-gated ion channels (ionotropic receptors) work?
The ligand binds to the receptor and the channel opens causing a Hyperpolarisation or depolarisation causing cellular effects This occurs in Milliseconds and an example is the Nicotinic ACh receptor
How do G-protein-coupled receptors (metabotropic) work?
Receptors are coupled to G-proteins and when the substate binds to the receptor the G-proteins can stimulate the ion channels to open them or activate enzymes to act as second messengers and complete different activities in the cell (E.g calcium release, protein phosphorylation) This occurs in seconds and an example is the Muscarinic ACh receptor
How do Kinase-linked receptors work?
The receptor/enzyme kinase is activated and can cause protein phosphorylation then gene transcription, resulting in protein synthesis causing cellular effects This occurs over hours and an example is the Cytokine receptors
How do nuclear receptors work?
Nuclear receptors often stimulate gene transcription in the nucleus which gives rise to new proteins which will give different cellular effects This occurs over hours and an example is the Oestrogen receptor
What is the time difference between pathways that do transcription in the nucleus and those that dont?
The pathways that do transcription in the nucleus are much slower and take minutes to hours than the ones that don’t which are fast and done in less than seconds to minutes
How are lipid soluble molecules transported inside cells?
They are bound by a carrier protein in the blood plasma as they are soluble. They detach from the binding protein and diffuse through the cell into the nucleus where they bind with a receptor and trigger transcription which causes a protein to be made and an altered cell function
How does cortisol work?
Cortisol is a lipid-soluble molecule which causes a conformational change and activates an intracellular receptor protein where the two bind to one another creating an activated receptor-cortisol complex which moves into the nucleus and binds to the regulatory region of the target gene to activate transcription.
What happens in the Inositol phospholipid signalling pathway?
- A signalling molecule activates a G-protein linked receptor which activates a G-protein subunit - This activates the enzyme phospholipase C which liberates two signalling molecules from Phosphatidylinositol 4,5-biphosphate (PIP2), a phospholipid found in the lipid bilayer - This creates inositol 1,4,5 triphosphate (IP3) and diacyglycerol (DAG) - The inositol 1,4,5 triphosphate (IP3) activates the Calcium channel on the endoplasmic reticulum causing a calcium influx inside the cell to activate PKC (Protein kinase C) and the binding of the diacyglycerol (DAG) also further activates the Protein kinase C (both substances are required to activate it)
What happens once protein kinase C is activated and what are the outcomes of these?
Substrates for PKC’s include; - tumour suppressor P53 (transcription factor) -> prevents tumour formation - Ca(v) 1.2 (calcium channel) -> heart muscle contraction - IKKa (cytokine) -> B cell activation (immune function)
Draw the pathway of Eicosanoid biosynthesis?
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How does Aspirin prevent arachidonate binding?
Aspirin acetylates (adds acetyl function group to) a serine hydroxyl group near the active site, preventing arachidonate binding. The inhibition by aspirin is irreversible. However, in most body cells re-synthesis of Cox-I would restore cyclooxygenase activity.
What are examples of anti-inflammatory drugs which target Eicosanoid pathways ? (Give the drug, type, mechanism and uses)
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