Term
| where are second messengers found? |
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Definition
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Term
| what are the benefits of multistep pathways? |
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Definition
multistep pathways can amplify a signal so a few molecules can produce a large cellular response.
they also provide more opportunities for coordination and regulation of cellular responses |
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Term
| in many pathways how is a signal transmitted? |
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Definition
through a cascade of protein phosphorylation
protein kinases transfer phosphates from ATP to protein, a process called phosphorylation. this occurs most commonly on serine, threonine (or tyrosine) residues |
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Term
| which enzyme removes phosphates from proteins in a process called dephosphorylation? |
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Definition
protein phosphotases
dephosphorylation = protein deactivation |
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Term
| the phosphorylation/dephosphorylation system acts a a molecular switch turning activities on, off or up and down as required. what is the activity of a particular pathway regulated by? |
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Definition
| the ratio of kinase to phophatase activity within a cell |
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Term
| second messengers are small ........... water soluble molecules or ..... that readily spread throughout a cell by ........... |
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Definition
nonprotein
ions
diffusion |
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Term
true or false?
second messengers participate in pathways initiated by GPCRs and RTKs |
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Definition
true.
Cyclic AMP and calcium ions are common second messengers |
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Term
| name one of the most widely used second messengers |
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Definition
cyclic AMP (cAMP)
adenylyl cyclase is an enzyme in the pm which converts ATP to cAMP in response to an extracellular signal |
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Term
| which enzyme can break down cAMP? |
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Definition
| phosphodiesterase breaks down cAMP to AMP which is inactive |
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Term
| other components of cAMP pathways are G proteins, ........ and protein kinases |
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Definition
GPCRs
cAMP usually activates protein kinase A, which phosphorylates various other proteins. |
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Term
how do G proteins provide further regulation of cell metabolism in second messengers
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Definition
| some inhibit adenylyl cyclase |
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Term
| what is the causative agent of cholera? |
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Definition
toxin from bacterium vibrio cholerae.
the bacteria colonise the small intestine (forming a biofilm) and produce an enzyme that acts as a toxin |
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Term
| what is the function of the G protein affected by vibrio cholorae? |
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Definition
| involved in regulating salt and water excretion. |
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Term
| cholera toxins activate a G protein. what is this G protein UNABLE to do? |
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Definition
hydrolyse GTP to GDP hence it is switched ON all the time.
consequence : constant activation of adenylate cyclase and contionous production of cAMP. |
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Term
| which transmembrane regulator is activated from high cAMP levels in cholera? |
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Definition
CFTR cystic fibrosis transmembrance conductance regulator.
this causes dramatic EFFLUX of chloride ion and water from infected cells leading to watery diorrhoea. |
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Term
| calcium ion act as .......... messengers in many pathways. calcium is an important 2nd messenger because cells can ............. its .............. under normal conditions intracellular calcium concentration is very .......... |
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Definition
second
regulate
concentration
low
at some concentration the intracellular level maybe 10,000 times lower than in the blood stream or plant cell wall |
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Term
| pathways leading to the release of calcium ions involve additional second messengers. what are thery? |
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Definition
Inositol triphosphate - IP3
Diacylglycerol -DAG
cytoplasmic calcium is actively pumped into the ER/mitochondria/chloroplasts to keep cytoplasmic conc of calcium ions low. |
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Term
| in the build up to the release of calcium a signalling molecule binds to a receptor activating which phospholipase? |
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Definition
phospholipase C
this then cleaves membrane phospholipid PIP2 into DAG and IP3 |
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Term
| how does IP3 get from the cytosol to the IP3 gated calcium chanel in the ER membrane causing it to open? |
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Definition
diffusion
calcium ions flow out down conc gradient causing cytoplasmic ca levels to rise. the calcium ions then activate the next protein in one (or more) signalling pathways |
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Term
| what is Calmodulin? (CaM) |
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Definition
a very specific calcium modulated protein with 4 ca+ binding sites
ca+ binding induces conformational changes allowing CaM to bind to other proteins causing activation or deactivation |
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Term
| proteins most often regulated by CaM are protein phosphatases and kinases but can you name two other molecules CaM also regulates? |
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Definition
the activity of adenyly cyclases and phosphodiesterases in cAMP formation/breakdown.
CaM also activates Ca2+ATPase which pumps Ca2+ out of cell to < Ca2+ concentration |
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Term
| a signal transduction pathway leads to the regulation of one or more cellular activities. where may this response occur? |
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Definition
in the cytoplasm or the nucleus
many signalling pathways regulate enzyme/protein synthesis by turning genes on/off in the nucleus |
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Term
| the final activated molecule in the signalling pathway may fuction as what? |
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Definition
| a transcription factor (eg, Ras pathway) |
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Term
| when fine-tuning a signal response what four things must we consider? |
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Definition
- amplifying the signal thus the response
- specifictiy of the response
- overall efficiency of response, enhanced by scaffolding proteins
- termination of signal
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Term
| what are scaffolding proteins? |
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Definition
they are large relay proteins to which other relay proteins are attacthed
these proteins can increase signal transduction efficiencey by grouping together different proteins invilved in the same pathway |
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Term
| with regards to termination of the signal, if ligand concentration falls then fewer receptors will be bound. which state are the unbound receptors in? (active or inactive) |
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Definition
inactive.
other inactivation mechanisms include Ca2+ and CaM who contribute to a negative feedback loop to reduce cytoplasmic Ca2+ levels |
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