What doesn't ATP spontaneously hydrolyze?

[Iatro]

Why doesn't ATP spontaneously hydrolyze? I understand that thermodynamically, a large amount of free energy is released per ATP molecule. deltaG is negative. I understand it doesn't spontaneously hydrolyze due to slow forward reaction (in H20). What are the molecular/cellular features that give rise to this low forward rate of reaction (kinetics)? Resonance? High energy barrier (if so due to what, or what are features of molecules with high energy barriers in general)?

EDIT: We have discovered one of the reasons has to do with cellular/compartment ATP/ADP/Pi concentrations (Le Chatlier's etc.!)

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[Cmdr_Shepard]

It has a negative delta G if you look at standard conditions. But in the cell the concentrations aren't standard. So much so that enzymes are required to catalyze the hydrolysis.

(By increasing the local concentration of ATP and by providing a place for that energy to go)

 

[sazerac]

This is a very good question and it is typically covered in the first week or two of a biochemistry course.

I don't want to pontificate on the answer because I might get it wrong, but there are three or four specific and testable reasons that the "hump" between ATP and ADP is so high and therefore the rate of the favorable reaction is so low.

 

[Iatro]

It has a negative delta G if you look at standard conditions. But in the cell the concentrations aren't standard. So much so that enzymes are required to catalyze the hydrolysis.

(By increasing the local concentration of ATP and by providing a place for that energy to go)

Hmm. I don't quite seem to get your answer as you are invoking kinetics to justify overcoming the thermodynamic shift due to the cell not being in standard conditions. I understand that cellular conditions aren't standard conditions, but it would still be negative no? I mean, it has to be exergonic for it to be the molecule of energy in cells. And I'm taking before we get to any enzyme action. Simply the ATP floating in the various cellular compartments before it is used. What are the intrinsic properties of ATP that prevent in from autohydrolyzing?

 

[Iatro]

This is a very good question and it is typically covered in the first week or two of a biochemistry course.

I don't want to pontificate on the answer because I might get it wrong, but there are three or four specific and testable reasons that the "hump" between ATP and ADP is so high and therefore the rate of the favorable reaction is so low.

Haha pontificate away. I remember at one point I knew the reasons in my biochem class, however this was 2 years ago and I have forgotten them. What are the 3-4 ideas you have? If I see them it might come back to me 😛

 

[Cmdr_Shepard]

Hmm. I don't quite seem to get your answer as you are invoking kinetics to justify overcoming the thermodynamic shift due to the cell not being in standard conditions. I understand that cellular conditions aren't standard conditions, but it would still be negative no? I mean, it has to be exergonic for it to be the molecule of energy in cells. And I'm taking before we get to any enzyme action. Simply the ATP floating in the various cellular compartments before it is used. What are the intrinsic properties of ATP that prevent in from autohydrolyzing?

Ah I see what you mean now. Remember that ATP exists in a very small quantity (as a fraction of total energy in a cell), and some is kept around for quick energy needs but for the most part it's generated as needed. This keeps it's concentration in the cell low and helps to shift the ATP/ADP equilibrium to ATP. This, combined with the initial activation E needed to go to ADP reduces the chances that free ATP will turn to ADP.

And even if it does, it's just making heat so likely there was no real evolutionary pressure to reduce this "leakage" further since heat is good.

 

[Iatro]

Ah I see what you mean now. Remember that ATP exists in a very small quantity (as a fraction of total energy in a cell), and some is kept around for quick energy needs but for the most part it's generated as needed. This keeps it's concentration in the cell low and helps to shift the ATP/ADP equilibrium to ATP. This, combined with the initial activation E needed to go to ADP reduces the chances that free ATP will turn to ADP.

And even if it does, it's just making heat so likely there was no real evolutionary pressure to reduce this "leakage" further since heat is good.

Yea I think I remember that now! ATP low concentration, Le Chatlier's etc. Hmmm but I thought there were more, like there was something specific in the structure of ATP itself that made in kinetically stable (giving rise to the high Ea like you said). I see where you are coming from and I agree in terms of total energy stored by a cell ATP is a rather low % (glycogen etc.) However would not the only concentrations influencing (or by far most heavily influencing) the equilibrium constant be simply the concentrations of Pi and ADP in the cell? Like the amount of glycogen wouldn't directly matter too much.

Haha I also like your "heat is good" comment. When you consider that what 60%(?) of energy in respiration is given off by heat, does that extra from ATP autohydrolysis really make a difference? 😛 Also, who knows when ATP was selected by evolution for its chemical/energy transferring properties, but I am assuming it was some prokaryotic a longgg time ago. Heat is good for humans, but would it have necessarily been good for them as well? 😛 Haha, when did "heat" become a feature that organisms actually began to select for? Warm blooded animals?

Diving a little further down the rabbit hole....what is the approximate turnover rate for the backbone structure of ATP in the body? I'm guessing it would be similar to that of an adenine nucleotide...which is? Or is it more similar to that of a vitamin?

 

[sazerac]

Haha pontificate away. I remember at one point I knew the reasons in my biochem class, however this was 2 years ago and I have forgotten them. What are the 3-4 ideas you have? If I see them it might come back to me 😛

Yeah I took biochem in 2011 :-/

Drat, the four reasons we are thinking of are the four reasons why ATP hydrolysis is exergonic (thermodynamics). They are outlined nicely in here: http://chemwiki.ucdavis.edu/Biological_Chemistry/Biochemical_Energy/ATP//ADP

Unfortunately the OP is asking about kinetics and I don't think anybody covers that in detail. Obviously if you start drawing out how exactly the electrons are pushed, there must be some really high energy transition states to make that big "hump", but as a second year med student ain't nobody got time fo dat.

Beware the explanations above with leChat and concentrations and stuff - that is thermodynamics ("will this reaction go forwards or backwards") and not what the OP is asking for, namely kinetics ("how fast will this reaction go").

 

[Hailstorm]

It does spontaneously hydrolyze, it's not a long-term method of bulk-storage - how efficient is anaerobic respiration relative to oxidative?. Keep in mind that cellular reactions are extensively catalyzed by various enzyme complexes, look up some protein structures to appreciate the effects.