Biol 224 Theme 4

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  1. Indirect(humoral) Cell Communication
    • -mediated by chemical ligands
    • -bind to specific recepetors in target cells/tissues
    • -slow in general with a prolonged response, (few hours-weeks)
  2. Hormones
    • -signalling molecules synthesized and secreted by specialized cells that are released into the blood and exert specific biochemical actions on the target cells located at distant sites
    • -produced by the endocrine glands
    • -also produced by the neurons=nuerohormones
  3. Growth Factors
    • -hormone like molecules released into interstitial space(ecm) exerting biochemical actions on target cells at close sites
    • -paracrine regulators
  4. Cytokines
    • -regulatory peptides
    • -not a "traditional" chemical messenger because they are not produced by a specialized gland
    • -can be made by almost any cell that has other primary function
    • -can exert local(paracrine) or distant(hormonal) effects
  5. Neurotransmitters
    • -produced by neurons that transmit signals across a synapse
    • -some can also have hormonal effects
    • -are secreted into a virtual compartment called a synapse 
    • -information is sent very fast and generally short lived(hormonal effects can last a long time)
  6. Neurons
    • -functional unit of the nervous system
    • -generate electrical and chemical signals
    • -chemical signals are termed neurotransmitters
    • -information is sent very fast and generally short lived
  7. Neuromodulation
    • -when neurotransmitter diffuse through large areas and regulate a diverse population of neurons of the CNS they are neuromodulators 
    • -contrasts to classic synaptic transmission(where 1 presynaptic neuron directly influences a single postsynaptic partner)
  8. Transient Direct Linkup
    • -immune cells have specialized markers on the cell membrane that allow transient interaction with cells that have compatible markers
    • -phagocytes use this to selectively destroy undesirable cells while leaving healthy cells alone
  9. Pheromones
    • -chemical signals released into the environment by an animals glands to affect sensory cells in other animals
    • -marking territory
    • -mating readiness
  10. Circadian Rhythms
    -based on a clock found in the superchiasmatic nucleus (SCN) of brain
  11. Signalling Molecules
    • -hydrophilic 
    • -lipophilic(require protein carriers)
    • -gaseous 
    • -in blood stream=hormone
    • -in synapse=neurotransmitter
  12. Structure of Signalling Molecules
    • -amines
    • -derived from Tryptophan and Tyrosine 
    • -some of the neurotransmitters 
    • -noradrenalin(norepinephrine, usually a neurotransmitter)
    • -adrenaline(epinephrine, usually hormone)
    • -serotonin
  13. Water Solubility
    • -most hormones
    • -neurohormones
    • -cytokines 
    • -growth factors
  14. Steroids
    • -cholesterol derivatives
    • -from gonads and adrenal cortex glands
    • -less soluble in water(require carriers)
  15. Retinoids
    • -derived from vitamin A
    • -mainly paracrine regulators
    • -involved in development and differentiation
  16. Eicosanoids
    • -derivatives of fatty acids
    • -paracrine regulators
    • -include prostaglandins which regulate smooth muscle actions among other effects
  17. Gases
    • -three inorganic gases thought to be toxic are now known to be messengers
    • -Nitric oxide, small and highly reactive paracrine signal molecule
    • -carbon monoxide, paracrine
    • -hydrogen sulfide, paracrine
  18. Signalling Receptors
    • -chemical messengers exert effects by binding to receptors
    • -messengers can have multiple meanings
    • -meaning/response to chemical messenger is determined by the receptor
  19. Ion Channel Linked Receptor
    • -upon ligand binding undergo a conformational change
    • -open channels to allow Na or K ion passage creating electrical charge
    • -open only briefly and then the ligand dissociates and the receptor is available for binding again
  20. Seven Transmembrane Receptors
    • -also termed G-proteins, coupled receptors
    • -cross the cell membrane 7 times
    • -associated with a group of regulatory G proteins(called G proteins because they bind to GTP)
    • -link the receptor with an intracellular effector enzyme
  21. Configuration of Seven Transmembrane Receptors
    • -extracellular glycosylated amino-terminal domain(contains binding site)
    • -transmembrane domain consisting of seven α helices made up of hydrophobic AA
    • -intracellular domain contains AA recognition sequences for the G-proteins also has a C terminal that can be phosphorylated for specific AA which regulate receptor activity
  22. Signalling in Seven Transmembrane Receptors
    -ligands bind causing the synthesis of an intracellular second messenger that sets off a cascade of phosphorylation reactions that dramatically amplify the extracellular signal
  23. Gαs (G-alpha-s)
    • -associated to effector enzyme adenylyl cyclase (AC) a transmembrane glycoprotein that catalyzes the conversion of ATP into second messenger cAMP
    • -three receptors are an example of same key different lock
  24. Gαi/o (G-alpha-i-or-o)
    • -also associated to adenylyl cyclase (AC) (Gαs also associated with AC) but inhibits synthesis of cAMP
    • -three receptors are an example of same key different lock
  25. Gαq/11 (G-alpha-q-or-11)
    • -associated to effector enzyme phospholipase C-β (PLCβ), a transmembrane protein that's function is to synthesize two second messengers, inositol(1,4,5) triphosphate and diacylglycerol through the membrane phospholipid, phosphatidylinositol
    • -three receptors are an example of same key different lock
  26. Signals to the Seven Transmembrane Receptors
    • -light sensitive compounds
    • -odours
    • -pheromones 
    • -hormones
    • -neurotransmitters 
    • -for these reasons the seven transmembrane receptors are a target for a large number of modern medicinal drugs
  27. Intracellular Signalling
    • -receptors located in the cytosol or nucleus are termed nuclear transcription factors hormone receptors 
    • -steroid hormone-receptor complex acts as a transcriptional activator to regulate gene activity 
    • -can influence a number of genes in a single cell or in different cells through cell-cell communication(gap junctions)
  28. Protein Kinase A Pathway
    • 1-extracellular first messenger binds to seven transmembrane receptor
    • 2-activates Gαs protein(based on first messenger)
    • 3-Gαs activates adenylyl cyclase (AC) which converts ATP to cAMP(second messenger)
    • 4-cAMP activates protein kinase A (PKA)
    • 5-PKA activates(phosphorylates) inactive target protein which brings about cellular response
    • -response is through massive amplification, from single first messenger to up to 10 million products of the final activated protein
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Biol 224 Theme 4
2013-10-05 19:03:48
Biol 224

Theme 4
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