ATP hydrolizes to ADP and phosphate in a strongly exergonic reaction and is used for energy transfer and short-term storage in cells.

ATP is stable inside a cell, so a significant activation energy must be necessary for the reaction.

However, the English Wikipedia article implies that stability of ATP is not a given, but depends strongly on the properties of the surrouding solution:

  • "ATP is highly soluble in water and is quite stable in solutions between pH 6.8 and 7.4, but is rapidly hydrolysed at extreme pH." and
  • "ATP is an unstable molecule in unbuffered water, in which it hydrolyses to ADP and phosphate."

How does the pH affect the hydrolysis of ATP? Why is it even relevant if the solution is buffered or not? (Do the ions stabilize the molecule somehow?) Are there other effects that influence stability in animal cells?

  • $\begingroup$ Welcome to Biology SE. This is a reasonable question, although perhaps more chemistry than biology. However I have altered the title to include the key factor you are concerned about — pH. That will help others know what your question is about, and thus whether they feel they may be able to help you. It is also important for archiving purposes. $\endgroup$
    – David
    Jul 25, 2016 at 20:10
  • $\begingroup$ Actually, It seems that both the right ph and the existance of a buffer in the solution is required, so that needs clarification as well. Sorry I asked two questions instead of one, but it might be related. I did not ask at Chemistry SE, as there might be something else going on inside cells that might influence stability of ATP. $\endgroup$
    – user25269
    Jul 26, 2016 at 6:43
  • $\begingroup$ I guess alkaline hydolysis will happen via a mechanism similar to alkaline hydrolysis of phosphodiester bond in RNA. $\endgroup$
    Jul 26, 2016 at 7:29
  • $\begingroup$ I've changed the title to the more precise hydrolysis, because that's what the Wikipedia quotes refer to. I would imagine @WYSIWYG is right about alkaline hydrolysis. I don't know about acid hydrolysis. $\endgroup$
    – David
    Jul 27, 2016 at 17:43
  • $\begingroup$ I'm not sure how the activation energy would be affected by pH, but it is well known that the equilibrium is shifted by pH since the various phosphates have different pKa values. See for example jbc.org/content/193/1/425.citation $\endgroup$
    – Roland
    Jul 27, 2016 at 21:21

2 Answers 2


OK. Let’s answer the questions you pose:

How does the pH affect the hydrolysis of ATP?

High concentrations of hydrogen ions or hydroxyl ions (“extremes of pH” — as you quote) cause acid or alkaline hydrolysis. The mechanism of alkaline hydrolysis is presumably through a cyclic intermediate, as with the hydrolysis of RNA. Acid hydrolysis of ATP requires very low pH — for example it has been studied in 3M perchloric acid — and the mechanism is quite complex, according to work published by Hutchings et. al. in 1981.

Why is it even relevant if the solution is buffered or not?

In unbuffered solutions the pH may easily deviate from the physiological range. This is a practical consideration of work in vitro. Physiological and cellular systems are highly buffered by a variety of ions and even macromolecules so the problem does not arise.

Are there other effects that influence stability in animal cells?

You are mistaken in your assumption that there is a particular need to prevent hydrolysis of ATP within animal cells. This appears to be based on a misunderstanding of a Wikipedia entry which is more concerned with the chemistry of ATP rather than its situation in the cell.

  • $\begingroup$ @TomD — ATP is an important metabolite, and its generation and the coupling of its hydrolysis to chemical, electrochemical and mechanical processes is important. Whether it is “the basis of life” any more than DNA, RNA, proteins, lipids, NAD etc. is an irrelevant and fruitless question. What I maintain is that the problems Nature had to solve with respect to ATP were those already mentioned. Its activation energy and chemistry are such that there is no tendency for its spontaneous hydrolysis at physiological pH, so preventing this is not a problem and certainly not the “the basis of life”. $\endgroup$
    – David
    Jul 29, 2016 at 13:39

Stability of ATP is largely due to Mg2+. ATP in cell is actually Mg2ATP2- The Mg ions stability the negative charges on the phosphates. pH is also important of course, but Mg is key, hence you see Mg2+ all the time in biochemical reactions where ATP is involved.

  • $\begingroup$ This is not an answer to the question. The question asked why extremes of pH affect the stability (the quote is for hydrolysis) of ATP. The fact that Mg ions interact with the phosphate negative charges has nothing to do with hydrolysis outside the range of pHs quoted. $\endgroup$
    – David
    Jul 27, 2016 at 17:38
  • $\begingroup$ @David. aside from the question " are there other effects that influence stability in animal cells. $\endgroup$
    – SciEnt
    Jul 27, 2016 at 22:13
  • $\begingroup$ Mg2+ is there as a counter-ion and is required so the ATP is in the right conformation to bind to the active site of enzymes. All this talk of "stability" is unscientific waffle. And the Wikipedia entry is of no relevance to biology talking about the need for buffers and suitable pH. That's the milieu of the cell. It's really the sort of thing a chemist would write about preparing solutions in the lab. $\endgroup$
    – David
    Jul 27, 2016 at 22:21
  • 2
    $\begingroup$ @ David: My question title was changed by a moderator. The answer matches my original question "Why is ATP stable in cells?". $\endgroup$
    – user25269
    Jul 28, 2016 at 6:47
  • $\begingroup$ @SciEnt: Thank you for your answer! Do you have any sources readily available? $\endgroup$
    – user25269
    Jul 28, 2016 at 7:05

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