Term
Describe the mechanism of protein hormone action I
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Definition
1. hormone binds to receptor on cell membrane
2. "Gs-alpha" activation, GDP exchanged for GTP, GS-alpha-GTP activates adenylyl cyclase (Gs-alpha has GTPase which turns the response off)
3. GS-alpha-GTP-cyclase i/c IC cAMP, phosphodiesterase hydrolyzes cAMP as part of the off mechanism
4. cAMP binds PKA, causing dissociatino of regulatory & catalytic subunits, activation of catalytic subunits
5. Catalytic PK i/c cellular activities by phosphorylation of cellular components --> hormone effects (e.g. phosphorylase-b-K activation, glycogen synthase inhibition)
ribosomes (i/c protein synthesis)
transport proteins (binding affinity, transport)
enzymes (active/inactive configurations) |
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Term
Describe the mechanism of protein hormone action II
examples? |
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Definition
1. Hormone binds to cell membrane receptor
2. --> hydrolysis of PIP2 to release IP3 & DAG
3. IP3 binds to intracellular R on ER --> ER releases Ca++ into cytoplasm
4. DAG activates PKC
5. DAG, IP3, Ca++ stimulate the entrance of more EC Ca++
6. I/c IC Ca++ binds calmodulin, Ca++-calmodulin activates enzymes (e.g. activation of myosin light chain K which phosphorylates myosin to contract smooth m)
NE action at a1 receptors initiating contraction of vascular smooth m by raising IC Ca++
ADH Acting at V1 receptors in vascular smooth m to i/c IC Ca++ --> contraction |
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Term
Describe the mechanism of protein hormone action III
examples? |
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Definition
Tyrosine Kinases - inc insulin, somatomedin, PDGF
External R is attached to IC tyrosin K (most function as dimmers)
When R is occupied, tyrosine K is activated to auto-phosphorylate, then P other IC pr responsible for hormone effect
With some receptors a free IC tyrosine K associates with the R after it's occupied
JAK-STAT system |
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Term
Describe the mechanism of steroid hormone action
examples? |
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Definition
Includes vit D, thyroxine
1. Lipid soluble steroids diffuse through cell membrane, bind to IC R located in cytoplasm or on nucleus
2. 3 domains of R: steroid binding site, DNA binding site (obscured by HSP), gene transactivating site
3. steroid/R --> alters sedimentation coeff of R, involves release of HSP
4. R may facilitate mvmt of steroid through the hydrophilic IC environment
5. S/R enters nucleus, forms dimer, binds to HREs on the csomes
6. nuclear binding i/c RNA synthesis, protein synthesis to produce hormone effects
Vit D i/c the synthesis of calbindin in intestinal mucosa, i/c absorption of dietary CA++ |
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Term
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Definition
Macromolecules
Binding affinity is proportional to the potency of the hormonal ligand
Binding is saturable
Binding is high affinity
Binding is stereospecific
Binding occurs at physiological hormone concentrations
Only a small fraction of the cell's receptors need to be occupied to elicit a maximum response |
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