Phosphoinositol Pathway and Calcium

Phosphoinositol pathway

Like a G protein coupled receptor with different g alpha subunit that is going to activate phospholipase C (instead of adenylyl cyclase)

phospholipase C produces DAG (stays in membrane) and IP3 (in cytosol)

-DAG activates PKC

-IP3 activates calcium channels

-Ca2+ also acts as a 2nd messenger by fully activating PKC and binding to calcium binding proteins like calmodulin that is then used to activate protein kinases

**main aspect of pathway: activate kinases

What does a phospholipase do?

cleaves glycerophospholipids

Are channels active or passive?

Always passive (high→low)

What must act together in order for protein kinase c to be fully activated?

DAG and calcium

Inactivation of Phosphoinositol Pathway

G alpha had GTPase activity to reset it

use phoshphatase to remove phosphates from active proteins

get calcium back into the ER or out of the cell to get those levels back down

get rid of IP3 by removing phosphate to turn it into IP2 which is inactive (inositol polyphosphate phosphatase)

What do we suspect that lithium does to the phosphoinositol pathway?

prevents the degradation of IP3 so it keeps signaling longer than it is supposed to

-lithium’s effective dose is really close to its lethal dose so it must be highly regulated and monitored when prescribed by psychiatrists (one of scariest drugs available)

Increases in cytosolic calcium concentrations can activate what kinds of processes?

-smooth muscle contraction

-exocytosis

-glycogen metabolism

Where in the cell are there intracellular reservoirs of calcium?

endoplasmic reticulum and calciosomes

-these are not released by cAMP → they respond to IP3

How many ligands does the EF hand domain have and what are they?

6 ligands:

-1 Glu

-3 Asp

-1carbonyl group from backbone

-1 H₂O

EF Hand Domain

resembles thumb and forefinger of right hand (helix-loop-helix)

has been identified im calmodulin, TnC (troponin), etc.

most EF-hand proteins possess 2+ EF-hand domains; arranged so that 2 EF-hand domains may directly contact each other