PC structure, reg, mech Flashcards
PC structure
4 domains per subunit.
Tetrameric is required, but only 2 are active at a time.
The assemblage of 4 subunits activates the ability to the job, but only want 2 to do it.
BC domain
catalyze Phase I, must bind ATP and HCO3- (bicarbonate)
allosteric domain
where Ace-CoA binds to activate PC. (Why? Ace-CoA = metabolite in TCA which produces a lot of energy, when Ace-CoA levels are high, organisms use PC to channel pyruvate away from TCA)
Regulated, large -∆G.
located in middle of BC and CT domains
CT domain
Catalyzes Phase II… big free energy drop.
alpha beta barrel.
has Zn cofactor, which may be responsible for the urido pull
BCCP domain
connects to biotin arm via lys
Apparent distance in 1 subunit
Large apparent distance to move CO2 to get it to the next subunit….
this distance is larger than the linker arm, so cant move arm in one subunit. Must move between subunits.
How that works:
BCCP domain of one subunit shuttles CO2 from BC domain of same subunit to CT domain on a 2nd subunit. These are about 65A apart… must put arm in the middle so it only has to go half the distance between the subunits.
MUST BRIDGE SUBUNITS by sending arms half one way and half the other
How are 2 of the 4 tetrameric subunits turned off?
Allosteric activation of only 2 subunits by Acetyl-CoA.
Also, negative cooperativity. When Acetyl CoA binds to two subunits, change in conf says to the other subunits saying that cant be active.
Why does any of this regulation happen?
OA is a crossroad metabolite, can be used in other pathways…
Regulators of OA
High [acetyl-CoA] means you need OA, strong allosteric activator.
OA + ACe CoA = citrate…
PC is inactive if Ace-CoA not bound.
- fasting and fed
fasting: need OA to run gluconeogenesis, and use b-ox to provide atp and nadh needed
fed: need OA to largely be used in TCA to produce E
Anapleurotic
filling up to a certain point. (toilet bowl rxn!)
In this case, it is supplementing oxaloacetate for various key biochemical pathways
