Exley cell signalling lecture 4 Flashcards
Why make Ins(1,3,4,5)P4 from Ins(1,4,5) to enhance the activity of Ins(1,4,5)P3?
Because Vmax of Ins(1,3,4,5) is 100 fold lower than Ins (1,4,5)P3
- so rate of breakdown is significantly lower for Ins(1,3,4,5)P4 and therefore will have a longer half life in the cell than Ins(1,4,5)
Define Vmax and when it occurs
Maximum velocity at which an enzyme can catalyse a reaction.
This occurs when a substrate is at a concentration that saturates the enzyme, and the conc of the enzymatic product is low
Ins(1,3,4,5)P4 serves as a short-lived memory that the cell had recieved at previous episode of InsP3, to allow the cell to respond differently to multiple stimulations, and therefore serves as a __________
coincidence detector
What is long term potentiation?
A type of coincidence detection - high frequency stimulation of a neurone increases the magnitude of subsequent responses (believed to underlie learning and memory)
where is IP5 located?
attached in the plasma membrane
where is IP3->IP4 located?
endoplasmic reticulum
What is the significance of IP4 acting as an antagonist at the IP3 receptor?
At high conc IP4 inhibits IP3 induced Ca2+ release from the ER
= Cytosolic Ca2+ spikes become more sharp, as the IP3 receptor is switched off, lowering Ca2+ release from cell
What is the significance of IP4 acting as an agonist at the IP3 receptor?
Activates Ca2+ entry channels (GAP1),leading to depletion of Ca2+ levels in the ER
What allows IP4 to act as both an antagonist and an agonist?
There are three isoforms of IP3 receptor in mammals, responding differently
What is the normal conc of IP4 in the cell?
1.0 microMolar
What are Ca2+ activated chloride channels in cells important in the control of?
Cell volume
Cell excitability
Cell secretion
An Ins(1,4,5)P3-generated increase in _____ Ca2+ concentration induces phosphorylation of CaCC (via ____) which increases the sensitivity of the CaCC to __-triggered opening.
Ins(3,4,5,6)P4 accumulates slowly in stimulated cells for 30 minutes or more and progressively inhibits ___-triggered opening of CaCC as its concentration increases in the range _____ mM.
An Ins(1,4,5)P3-generated increase in cytosolic Ca2+ concentration induces phosphorylation of CaCC (via CAMKII) which increases the sensitivity of the CaCC to Ca2+-triggered opening.
Ins(3,4,5,6)P4 accumulates slowly in stimulated cells for 30 minutes or more and progressively inhibits Ca2+-triggered opening of CaCC as its concentration increases in the range 3 – 10 mM.
How does concentration of IP4 increase slowly?
IP3 is the substrate for the dual specificity kinase which removes IP4, so it is inhibited when IP4 degrades to IP3
What inositol polyphosphate kinase makes and destroys IP4? and how
ITPK1
- The enzyme can use ATP to interconvert IP(3,4,5,6)4 and IP(1,3,4,5,6)5
