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34 Cards in this Set
- Front
- Back
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What is signal transduction?
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Mechanism by which cells detect, amplify and process extracellular signals into a physiological response
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What are the classes of Hormones(4)?
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Peptides:insulin and flucagon synthesizes in pancreatic cells
Catecholamines: epinephrine and norepi released by adrenal gland and CNS Steroids: glucocorticoids progestins made from cholesterol Thyroids: triiodothryonine t3 and t4 derived from protein bound tyrosine and iodine |
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What are some NT?
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Acetylcholine, catecholamines, and gaba
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What are some Eicosanoids:
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Prostaglandins, Leukotrines, synthesizes from 20 C FA
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How can hormone regulate enzymes?
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Covalent Modification via phosphorylation and dephos
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What is a G-protein coupled receptor?
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Is a protein that has an external receptor, a seven transmembrane domain and an intracellular domain the binds to the G protein
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What is an example of a g-coupled receptor?
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B-adronergic receptor
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what are the agonist that bing to g protein?
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Acetylcholine, epi, norepi etc...
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What is a G protein?
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Its a membrane protein that binds GTP. Its role is to relay a message from the receptor to the effector.
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What are the two types of G proteins?
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Monomeric:single subunit and heterotrimeric which has an A B and Gamma subunit.
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What does the alpha subunit bind?
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GTP or GDP
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What happens when the A-subunit is bound to GTP OR GDP
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GDP all three subunit bound together and the protein is inactive/
GTP bound a-subunit causes a-dissociation and activation of the effector protein which generates a second messenger. |
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What are examples of Monomeric G proteins?
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Ras, Rho, Rab, Ran ARF etx...
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Does the a-subunit have intrinsic GTPase activity?
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Yes
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What are the heterotrimeric g proteins?
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Gs-stimulates AC
Gi- inhibits AC Gq- Stimulates phopholipase C beta Gt- transducin stimulates cGMP phosphodiesterase (PDE) |
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What is the steps involved in the coupling of B-adrenergic receptor to adenylate cyclase and the cycling of Gs-proteins?
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1)So Epi bind to B-and receptor and causes a conformational change to receptor and g protein
2) GDP on a-subunit switch to GTP and A-sub dissociates and now is active 3) A-GTP stimulates AC which generates cAMP in the sell 4) b and g subunits also activate their own effector protein 5:Then GTP is hydrolyzed and converted back to the GDP state and abg subunits all join and signal is terminated |
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What does AC do
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it make cAMP from ATP and then phosphodiesteraze(PDE) hydrolyzes the phosphodiester bond to generate 5'-AMP
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What inhibits Phosphodiesterase(PDE)
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methylzanthines like caffeine and theophylline
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What is theophylline used for?
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treatment of Asthma
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What does forskolin do?
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Directly activates AC which elevates cell cAMP levels
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What is protein kinase A dependent on?
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cAMP
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what PKA made up of?
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2 catalytic and two regulatory subunits
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are the four subunits bound to PKA when inactivated?
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YEs
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What happens to PKA when c AMP binds to the R subunits?
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the c subunits are released which become active and then the C subunits phosphorylate Ser/Thr residues in many nuclear and cytoplasmic proteins changin their activity.
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What are the hormones that stimlate cAMP levels?
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Epi, glucagon, ACTH, vasopressin, FSH, TSH, LH
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What are some inhibitory Hormones of cAMP levels?
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ACetylcholine (muscarinic) Epi (alpha 2) Ang II and Somatostatin
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What enzymes are phosphorylated by PKA
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Glycogen Synthase, Pyruvate kinase (liver) Inhibited
Phosphorylase kinase, Hormone sensitive lipase, phosphatase inhibitor I, tyrosine hydroxylase Activates |
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How is AC controled?
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By Gs or Gi membrane linked receptors.so in the cell there is a balance between the activation of Gs and Gi
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What is special about the cAMP signaling
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Its a cascade event so for every receptor activation many Gs proteins are activated and even more AC activated and hundreds of cAMP are generated and then PKA is activated and then thousands of enzymes and phosphorylated
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What are the mechanisms that allow for the rapid turning off response of cAMP?
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Dissociation of the hormone from receptor, receptor desensitization, receptor internalization and receptor downregulation.
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What is BARK? what does it aid in?
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B-andrenergic receptor kinase, which phophorylates the recepttor causes receptor desensitization by the binding of arrestin to the receptor. so receptor can be bound by hormone but no activation of Gs
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How does CHOLERA cause explosive diarrhea?
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the toxin binds to the Ganglioside GM1 receptor on cell surface.
Then A1 subunits of the toxin enter the cell which then takes the ADP ribose from NAD+ and transfers it the GsAlpha subunits So now the Gs subunits binds to GTP but its GTPase activity is lost so it is now always turned on causing stimulation of AC which causes huge amounts of cAMP whic stimulates Na+ and H20 efflux from cells causing massive explosion |
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How does whooping coughs work?
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like cholera the toxin ADP ribosylates the alpha subunit of the Gisubunit and now it cant exchange GDP to GTP so now Gi is inactivated and cant inhibit AC which in the respiratory system causes large mucus secretion which makes you whoopy
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How does Diptheria work?
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the toxin ADP-ryboslates the EF-2 small monomeric g protein with is crucial in mRNA protein synthesis and then cell dies
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