lecture 1 biochemistry (week 1) Flashcards
what is the resting Ca concentration within the cell?
100nm
what is the resting Ca concentration outside the cell?
20,000 and 100,000 fold higher than 100nm
where is Ca actively pumped to?
The ER, mitochondria, and extracellular space.
how does the Ca concentration affect signal transduction?
changes affect transduction differently - rapid transient versus slow and sustained - mediate different events
what does the Na & Ca antiporter do?
transports Ca outside the cell and Na into the cell
what is the ER? describe four key features.
the ER is an organelle
that forms a network of
membrane sacs or tube like structures (cisternae)
membrane continuous with the outer membrane
biggest organelle per volume
efficient store
what does Ca bind to? and where?
binds to storage proteins in the ER - so high Ca = calsequestrin
what is calsequestrin?
calsequestrin is a calcium-binding protein that acts as a calcium buffer within the sarcoplasmic reticulum.
how much ions move across the membrane when the channels are opened?
10^6 of ions across the membrane
how much ions move across the membrane in antiporters?
1000/s
how can an increase of Ca be caused?
certain GPCRs trigger an increase
caused by an opening of a Ca channel in the ER
describe the steps after an increase in Ca is detected.
signal molecules activate their receptor –> activated subunit activates phospholipase C –> PhC breaks down PiP2 into diacylglycerol and IP3 –> PKC binds to diacylglycerol –> activates PKC –> IP3 opens channel –> Ca binds to PKC
what are the domains of PKC?
C1A and C1B domains of PKC (regulatory)
what molecules bind to these domains?
DAG binds to C1A and C1B domains (regulatory)
describe the mechanism of action of Ca binding to PKC.
Ca binds to C2 domains of PKC (catalytic) –> changes shape of PKC and encourages binding to the membrane –> links PKC to phosphatidylserine
how is the overall signalling process regulated?
the binding of DAG + C1B binding activates the kinase (conformational change)
localised and activated by two events = no accidents
what does an increase of ATP cause?
a closing of the ATP sensitive channels and depolarisation of the plasma membrane
what does a depolarisation of the membrane cause?
an opening of the voltage gated ion channels and a rapid influx of calcium
what does the rise of calcium cause in relation to insulin?
fusion of insulin containing vesicles with the PM
what two classes of drugs make up 60-70% of all prescription drugs for high BP in the UK and the US?
Ca channel blockers and ACE inhibitors
what is the drug bill of these two for the NHS? how much is estimated to be saved?
drug bill is < £200m but saves £250m in heart attacks
what does the sinoatrial node initiate?
initiates heart beat
describe the mechanism of action of CCBs
CCBs slow down heart beats and lets left ventricle fills completely which lowers the heart workload
what do CCBs reduce?
the force of contraction and reduce the constriction of arteries
