Term
| How many transmembrane protein domains does a GPCR have? |
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Definition
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Term
| What happens when a ligand binds to a GPCR? |
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Definition
| causes GPCR to change conformation (also causing G prodien subunits to change conformation) Alpha subunit dumps it's GDP and binds with a GTP (therefore it's a GEF) |
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Term
| whan is a G-Protien activated? What happens? |
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Definition
| at nucleotide exchange! Alpha and GTP separate from Beta&Gama; each of those binds with a different effector |
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Term
| Why dont G protein subunits interact with effectors in a bound state? |
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Definition
| b/c their active sites are facing eachother |
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Term
| What are the 4 major Galpha families? |
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Definition
Gs activates adenylate cyclase
Gi inactivates adenylate cyclase
Gq activates phospholipase C
G12/13 activates small g proteisn |
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Term
| What do Beta and Gama G-Protein subunits affect? |
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Definition
ion channels
adenylate cyclase
phospholipase C |
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Term
| This protein catylizes the hydrolysis of GTP on the A subunit. What kinda protein is it? |
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Definition
RGS (Regulator of G signaling)
GTPase |
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Term
| 2 mechanisms to desensitize GPCRs |
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Definition
heterologous desensitization (PKA and PKC phosphorylate GPCR so that G protein cannot rebind--ligand cant bind either!)
homologous desensitzation (free beta subunits bind GRK that phosphorylate ligand bound CPCRs, which bind arrestins) |
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Term
| What happens to a GPCR that is bound to arrestin? |
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Definition
| It has to be either dephosphorylated or broken down |
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Term
| How do Beta Blockers work? |
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Definition
| Bind to GCPRs of beta andergenic receptors, prevenintg the response (up cardiac output and blood pressure, dialation of skeletal and muscular arteries, gluco and glyconeogenesis) |
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Term
| How does the pertussis toxin work? |
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Definition
ADP ribosylzation of the (alpha I) unit of G protein,
it now canout couple to ligand bound receptor (cant be activated), cell cannot inhibit a nl cellular process |
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Term
| This is a mutation in the parathyroid GPCR that doesnt allow Gprotein to rebind resulting in hypercalcemia and increased bone reabsorbtion. Why does this happen? |
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Definition
Jansen's metaphysical chondrodysplasia
its PTH receptor activated, even when hormone isnt present |
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Term
| describe the opiate dose and effect curve |
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Definition
over time, user becomes desensitized to the effect of the drug, so more must be taken to reach the desired effect, however eventually, the dosage eccedes the lethal dose
OR person quits drugs for a while then becomes resensitized. They take the same amount that they used to while desensitized and BAM. dead. (LETAL Effect) |
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Term
| whats the difference between G-proteins and second messengers |
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Definition
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Term
| why are second messengers used? |
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Definition
easy to produce
diffuse easily throughout the cell for signal amplification |
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Term
| what are the 6 second messengers we mentioned in class |
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Definition
cAMP
cGMP
IP3
Ca++
diacylglycerol
NO* |
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Term
| what is the most common protein for G (alpha)s and GTP bind to? what does it make? |
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Definition
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Term
| this is the typical inhibitor of adenityl cyclase |
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Definition
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Term
| what does cAMP activate (usually)? How? |
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Definition
PKA (protein kinase A)
cAMP binds to the R (regulator) bound subuints, which relases the catalytic subunits |
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Term
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Definition
phosphorylizes GPCR
phosphorylizes metabolic enzymes to inhibit glycogenesis and stimulating glyconeolysis and gluconeogenesis
binds to CREB (camp response element biding which is a transcription actor for genes containing cAMP response elements
Phosphorylates CFTR increasing salt and H2O transport |
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Term
| How does the cholera toxin work? |
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Definition
vibrio cholerae ribosylates Galphas therefore it cannot hydrolyze GTP and it is always active
This leads on to a build up of cAMP and unregulated PKA activity. CFTR channel is always open CL then Na then H2O leave. You know the rest of the story
(chronicphosphorlyation of CFTR) |
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Term
| What triggers testostrone production in Leydig cells? |
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Definition
| LH binds to LHR and activates G alpha s, the rise in cAMP triggers testostrone production |
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Term
| What is PLC? What activates it? |
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Definition
lipase that cleaves PIP2 into GAD and IP3
activated by G alpha q and beta-gamma subunits released by G alpha i
other isoforms by tyrosine kinases and small G proteins |
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Term
| After PIP2 is cleaved, what happens next? |
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Definition
PKC binds to DAG (partial activation)
IP3 binds to IP3 receptors in teh ER leading to Ca++ release.
Ca++ binds to PKC leading to full activation
PKC phosphorylates a buch of shit |
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Term
| 3 other pathways Ca++ is involed in |
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Definition
activates phospholipase A2
generated 2nd messengers in inlamatory response
regulates adenetyl cyclases activity
to calmodulin a Ca++ binding adaptor protein which controls the activity of calmodulin dependent kinases and phosphatases |
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Term
| what does endothelial nitric oxide synthase do (what to what)? |
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Definition
| arginine and O2 are converted to citrulline, water and NO |
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Term
| How does NO* promote smooth muscle relaxation |
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Definition
| NO is a gas and diffuses to from endothelial cell (where NOS is located) smooth muscle where it agtivates guanylate cyclase which converts GTP to cGMP which is a 2nd messenger promoting vasodilation (SM relaxation) |
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Term
| How is eNOS regulated? Why is this good? |
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Definition
by Ca++
bc too much is toxic (think chew till you get a headache) |
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Term
This is the protein on immune cells that produces lots of NO to kill invaders.
How is it regulated? |
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Definition
iNOS (in response to cytokines)
mRNA is degraded very quickly |
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Term
| How is cAMP down regulated? |
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Definition
Phosphodiesterase (PDE) cleases a bond of cAMP to generate AMP. as cAMP goes down, regulatory elements of PKA lose camp and re-associate with catalytic elements.
there are also PDEs for cGMP |
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Term
| How is PKC downregulated? |
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Definition
DAG and IP3 metabolized
as IP3 goes down its receptors close
as DAG decreases, membrane and activation of PKC decreases |
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Term
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Definition
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Term
| How is free Ca++ downregulated |
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Definition
| quickly taken up by calmodulin and associated proteins |
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Term
| how do calcium channel blockers work? Name 2 |
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Definition
block calcium channels, muscle contractablity is inhibited, dilation of the arteries
cerapamil and nifedipine |
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Term
| How does Nitroglycerine treat angina or hypertensive emergencies |
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Definition
| bypasses the NOS enzyme and converted to NO, activates GC leads to increased levels of cGMP and vasodialation/smoothmuscle contraction |
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Term
| How does viagra work? Why cant it be used for cardiac muscle? |
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Definition
Viagra mimics cGMP and competitivly interderes with the binding of cGMP to PDE. Leading to prolonged vasodialation and BONER
It doesnt work with cardiac PDE isoform |
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Term
| What is the most important thing to remember about signal transduction? |
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Definition
| its not linear, many factors combine to create a large variety of different outcomes. |
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Term
| 2 downstream events of GPCR binding w ligand? |
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Definition
| gentransciption or cellular response |
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Term
| Take away from the isoproterenol, epi and norepi binding curves? |
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Definition
| Different structures elicit different degrees of cellular response |
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Term
| How do G-proteins become inactive? |
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Definition
| Aplha subunit has GTPase capability |
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Term
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Definition
cAMP activates it as well as adenetyl cyclase
GEF for a small G protein (activator) |
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