Lipids And Cel Membranes Flashcards
Cell to cell communication
Synthesis of signal
Release of signalling molecule by exocytosis diffusion to cell to cell contact
Transport signal to target cell
Detection by receptor protein
Change in cellular metabolism, function etc
Removal of signal or desensitisation
Two types of signalling
Long range and short range
Long range signal
Endocrine
Neurotransmitters
Endocrine
Where hormones is released by endocrine cells and carried in bloodstream to distal target cells
Example FSH released form pituitary acts on ovary
Example of neurotransmission
Breathing phrenic and thoracic nerves send impulses from brain to diaphragm
Short range signalling
Paracrine
Autocrine
Membrane bound proteins interact
Paracrine
Signalling molecules only affect cells in close proximity to secreting cell
Ex somatostatin release by pancreas acts locally as can neurotransmittion be local
Autocrine
Cells respond to substances that they themselves release
NT and Growth factors bind to cells that release them
Membrane bound proteins interact to signal
Signaling by plasma membrane attached proteins
Ex signalling by T cells in immune systems
Ex of multiple types of signalling occurring simultaneously
Insulin released form pancreatic beta fuels acts in autocrine paracrine and endocrine matter
Lipid soluble signalling molecules
Bind inteacellular receptors rest bing to membrane bound receptors on surface
Examples of cell surface receptor
Ligand gated ion channels
G protein coupled receptor
Kinase liked receptors
Example of intracellular receptors
Nuclear receptors
Signals that alter protein function are
Fast
Signals that alter protein synthesis are
Slow
Altered protein synthesis or function work by
Altering cytoplasmic machery and hence altering cel behaviour
Examples of lipid soluble molecules
Cortisol
Estradiol
Thyroxine
Testosterone
What happens during lipid molecule synthesis
Cortisol passes through plasma membrane
Reacts with intracellular receptor protein causing conformational change
Can now pass through into nucleus
Complex activates target gene via regulatory region causing transcription to occur
Inositol phospholipid signalling pathway
PIP2 is phospholipid found in enzyme bilateral
Substrate of enzyme phosplipase C (plc)
Plc liberates two signalling molecules from PIP2 - IP3 and DAG
Opens calcium channel
What happens to calcium in response to IP3 release
Calcium conc inc in cell
Calcium binds to protein to regulate their function
Substrates for PKC to activate it are
Tumor suppressor p53. Prevents tumor formation
CAv 1.2 - heart muscle contraction
IKKa - B cell activation
What happens to IP3 after signal
Referred back to membrane as PIP2
What are eicosanoids (prostanoid)
Inflammatory mediators
Local hormones - specific effect on target cel close to site of formation
Rapidly degradedo so not transported to distal sites within the body
Main eicosanoids (prostanoids)
Prostaglandins
Theomboxanes
Leukotrienes
20C with double bonds
Source of eicosanoids
Arachidonic acid (20:4)
Biosynthesis of eicosanoids
Initial and rate limiting step
Liberation of arachidnoic acid by phospholipids A2 PLA2
PLA2 Serotonin receptors Glutamate receptor 1 Some cytokine receptors An increase in calcium
How can arachidonic scid be metabolised
Cyclooxygenase and peroxidase to give prostaglandins and theomboxanes
Lipocygenases to give leukotrienes
Prostaglandins
Synthesised in all tissue and cell types
Vasoconstriction dilation
Inhibitor promote platelet aggregation
EP1 - vasoconstriction
EP2 - vasodilation
Inflammatory response. Thermoregulation fever and pain
Thromboxanes
Synthesised in platelets clotting
Short lived
Thromboxane A2 TXA 2 had prothrombotic properties
Stimulate platelet aggregation
Vasoconstrictor
Leukotrienes
Synthesised in WBC and contain double bonds
Some contain cystine in structure - anaphylactic shock
Heavily implicated in Asthma and allergy
Platelet activating factor
By product of arichdonic acid liberation not an eicosanoid
Synthesised in leukocytes and injured tissue
Platelet aggregation
Vasoconstriction
Inflammation
Immune response
What are NSAIDs
Inhibit cuclooxugenases and hence the formation of prostaglandins involved in pain fever and inflammation ( blockchannel where arschidonste enters COX active site)
Inhibit blood clotting by clocking thrombocytes tmformstion in blood platelets
How does aspirin work
Acetylates serine hydroxyl group preventing aracidonate bidning
IRREVERSIBLE
resybthesis of COX1 to restore activity
Aspirin anticoagulant
Thirnboxnae A2 stjualtes blood platelet in clotting
COX1 inhibiton - inhibition of theomboxane formation
Long lived because platelets lack nucleus and connor make new enzyme s
Aspirin
Cox1 inhibitin
Dexamethasone
Glucocorticoid
Inhibitos cox2 induces PLAw inhibitor
Arthritis chemotherapy
Iloprost
Activates prostacyclin receptor
Pulmonary hypertension
Zileuton
5-lipoxygenase inhibitor and his inhibits leukotriene synthesis
Asthma
Zafirukast
Inhibits leukotriene by blockingrecepto
Asthma
Dipyridamole
Inhibits thromboxane A2 synthesis
Pulmonary hypertension
Stoke pretentious with aspirin
