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I know that when ATP is more then it inhibits PFK and hence regulate the number of ATP. But how does PFK reactivates itself? Is it due to removal of ATP from allosteric site that just reconfigures the enzyme back to normal functional state, or does binding of AMP (after ATP removal) does that?

To clear the meaning,

PFK+ATP= (inactive PFK+ATP)

So is it (1) or (2)?

(1) (inactive PFK+ATP) => (Active PFK)+ATP

(2) (inactive PFK+ATP) => (Inactive PFK)+ATP removed => (Inactive PFK)+ attached AMP => (Active PFK) + removed AMP

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This is clearly explained on the Wikipedia page for glycolysis under the heading Phosphofrucokinase. AMP is an allosteric activator of the enzyme and ATP competes for binding at the same site but is not an activator.

You should think of the interaction between the two regulators in terms of reversible binding of both: since they compete for binding at the same site the proportion of the enzyme with bound AMP will go down if [ATP] goes up, for example.

Neither of your proposed schemes is correct: the enzyme is more active with AMP bound and less active with ATP bound. The idea that AMP binds, activates, then wanders off is wrong.

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I know that when ATP is more then it inhibits PFK and hence regulate the number of ATP.

This is correct. High levels of ATP cause an inhibitory effect on PFK, specifically brought about by ATP binding to an allosteric site on PFK. By ATP binding to the allosteric site of PFK, the energy state of PFK significantly increases. Illustrated below are the active and allosteric sites of PFK that ATP (and AMP) interact with.


PFK and its binding sites

When ATP allosterically binds to PFK, the rate in which it also binds to the active (catalytic) site(s) of PFK drastically decreases (which is due to PFK already having such a high energy state).


But how does PFK reactivates itself? Is it due to removal of ATP from allosteric site that just reconfigures the enzyme back to normal functional state, or does binding of AMP (after ATP removal) does that?

Well, it doesn't reactivate itself! Instead, AMP directly competes with ATP to bind to the allosteric site(s) of PFK. When this occurs, the binding of AMP causes the energy state of PFK to then again lower, which in turn promotes the binding of ATP to the active site(s) of PFK. It is this ongoing ratio of allosteric AMP:ATP binding to PFK that regulates PFK during this stage of glycolysis.

National Center for Biotechnology Information, U.S. National Library of Medicine

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  • $\begingroup$ The allosteric effectors of PFK change the affinity of the enzyme for F6P not for ATP - your reference mentions this. And that's what your second Figure relates to: it doesn't say anything about ATP binding at the active site, it shows that ATP reduces the rate of reaction at any given concentration of F6P. $\endgroup$ – Alan Boyd Aug 17 '17 at 18:36
  • $\begingroup$ @AlanBoyd Ah, yes, my mistake. I'll make the appropriate edit. Thanks for pointing this out. $\endgroup$ – Charles Aug 17 '17 at 18:39
  • $\begingroup$ 'ATP doesn't "attach and then come off" of PFK' -- this sounds the off-rate for ATP is zero (irreversible binding) which is probably not what you meant to say ... $\endgroup$ – Roland Aug 18 '17 at 6:51
  • $\begingroup$ @Roland Thanks for pointing this out to me.. I'll be sure to make the appropriate edit here shortly. :) $\endgroup$ – Charles Aug 18 '17 at 8:52

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