Why are three phosphate groups (such as in ATP) required for release of energy, but not two (ADP) or one (AMP) phosphates? How does breaking the phosphate bond release energy?

  • $\begingroup$ Your premise is flawed - ADP is used as a power source in some reactions. $\endgroup$
    – Luaan
    Commented Sep 21, 2015 at 18:42

2 Answers 2


Let me add to iad22agp's excellent answer.

Often times in introductory biochemistry classes, the difference between phosphoanhydride and phosphate ester bonds is not adequately explained.

ATP (and ADP) contain phosphoanhydride bonds. In these bonds, two phosphoric acid groups are condensed into one:

$\ce{R~-H2PO3 + R'~-H2PO3 -> R-HO2P-O-PO2H-R' + H2O}$

In contrast, AMP and many other phosphate-containing biomolecules such as glucose-6-phosphate glyceraldehyde-3-phosphate, contain phosphate ester bonds, where a phosphate group is condensed with an alcohol:

$\ce{R~-H2PO3 + R'OH -> R-HPO2-O-R' + H2O}$

Just as "regular" (i.e. carboxylate) esters like ethyl acetate are more stable to hydrolysis than carboxylic anhydrides (e.g. acetic anhydride), phosphate esters are much more stable and "lower energy" than phosphoanhydride bonds. They don't have enough energy to power many of the key reactions of biosynthesis. So that explains why AMP isn't a good energy source.

(By the way, mixed phosphate-carboxylate anhydrides are as high or higher in energy as phosphoanhydride bonds. Examples from biochemistry include acetyl phosphate or phosphoenolpyruvate.)

So ATP has two phosphoanhydride bonds. And as iad22agp mentioned, the electrophilic nature of the central P atom makes the outermost phosphoanhydride bond especially prone to hydrolysis. However, ADP still contains a high-energy phosphoanhydride bond. Consider this reaction:

$\ce{ATP + AMP <=> 2 ADP}$

The equilibrium constant for this reaction is about $2.82$, meaning the rightward "forward" direction is favored, but not by a whole lot. So the "extra" energy of ATP's particularly high-energy phosphoanhydride bond is not really that much higher than that of ADP's regular run-of-the-mill phosphoanhydride bond.

There are somewhat rare examples where ADP powers key metabolic reactions but ATP does not. That shows it is nearly as good an energy source as ATP.

The reason that ATP is so prevalent is probably because of evolutionary reasons. Also, another trick that enzymes used with ATP is sometimes to hydrolyze the interior phosphoanhydride bond, leading to AMP and pyrophosphate. Because pyrophosphatase enzymes quickly degrade pyrophosphate to two free ortho-phosphate groups, this trick effectively makes what would have been a reversible reaction effectively irreversible. That trick doesn't work with ADP because it has only one phosphoanhydride bond.


Think of ADP and ATP as substituted phosphoric anhydrides. ATP has a strong tendency to hydrolyze due to the electrophilic nature of the central phosphorus atom which bears two electron-deficient phosphate leaving groups. (note that ADP has only one, and is a poorer source of energy, whereas AMP has only a normal phosphate ester linkage.) ATP is kinetically relatively stable to hydrolysis in the absence of an enzyme (which would simply waste the energy as heat), but a wide variety of enzymes are able to couple the ATP hydrolysis reaction so as to drive various reactions or other processes.


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