ATP structure, ATP hydrolysis to ADP, and reaction coupling.


A cell can be thought of as a small, bustling town. Carrier proteins move substances into and out of the cell, motor proteins carry cargoes along microtubule tracks, and metabolic enzymes busily break down and build up macromolecules.
Even if they would not be energetically favorable (energy-releasing, or exergonic) in isolation, these processes will continue merrily along if there is energy available to power them (much as business will continue to be done in a town as long as there is money flowing in). However, if the energy runs out, the reactions will grind to a halt, and the cell will begin to die.
Energetically unfavorable reactions are “paid for” by linked, energetically favorable reactions that release energy. Often, the "payment" reaction involves one particular small molecule: adenosine triphosphate, or ATP.

ATP structure and hydrolysis

Adenosine triphosphate, or ATP, is a small, relatively simple molecule. It can be thought of as the main energy currency of cells, much as money is the main economic currency of human societies. The energy released by hydrolysis (breakdown) of ATP is used to power many energy-requiring cellular reactions.
Structure of ATP. At the center of the molecule lies a sugar (ribose), with the base adenine attached to one side and a string of three phosphates attached to the other. The phosphate group closest to the ribose sugar is called the alpha phosphate group; the one in the middle of the chain is the beta phosphate group; and the one at the end is the gamma phosphate group.
Image credit: OpenStax Biology.
Structurally, ATP is an RNA nucleotide that bears a chain of three phosphates. At the center of the molecule lies a five-carbon sugar, ribose, which is attached to the nitrogenous base adenine and to the chain of three phosphates.
The three phosphate groups, in order of closest to furthest from the ribose sugar, are labeled alpha, beta, and gamma. ATP is made unstable by the three adjacent negative charges in its phosphate tail, which "want" very badly to get further away from each other. The bonds between the phosphate groups are called phosphoanhydride bonds, and you may hear them referred to as “high-energy” bonds.

Hydrolysis of ATP

Why are the phosphoanhydride bonds considered high-energy? All this really means is that an appreciable amount of energy is released when one of these bonds is broken in a hydrolysis (water-mediated breakdown) reaction. ATP is hydrolyzed to ADP in the following reaction:
ATP+H2OADP+Pi+energy\text {ATP} + \text {H} _2 \text {O} \leftrightharpoons \text {ADP} + \text P_i + \text {energy}
Note: Pi\text {P}_i just stands for an inorganic phosphate group (PO43)\text{(PO}_4^{3-}\text).
Like most chemical reactions, the hydrolysis of ATP to ADP is reversible. The reverse reaction, which regenerates ATP from ADP and Pi\text P_i, requires energy. Regeneration of ATP is important because cells tend to use up (hydrolyze) ATP molecules very quickly and rely on replacement ATP being constantly produced1^1.
Image of the ATP cycle. ATP is like a charged battery, while ADP is like a dead battery. ATP can be hydrolyzed to ADP and Pi by the addition of water, releasing energy. ADP can be "recharged" to form ATP by the addition of energy, combining with Pi in a process that releases a molecule of water.
You can think of ATP and ADP as being sort of like the charged and uncharged forms of a rechargeable battery (as shown above). ATP, the charged battery, has energy that can be used to power cellular reactions. Once the energy has been used up, the uncharged battery (ADP) must be recharged before it can again be used as a power source. The ATP regeneration reaction is just the reverse of the hydrolysis reaction:
energy+ADP+PiATP+H2O \text {energy} + \text {ADP} + \text P_i \leftrightharpoons \text {ATP} + \text {H} _2 \text {O}
You may be thinking: doesn’t ADP still have a high-energy phosphoanhydride bond left? Yes, it does, and under some circumstances, that bond may be hydrolyzed as well to release more energy (generating adenosine monophosphate, AMP, and inorganic phosphate).
We’ve mentioned that a bunch of free energy is released during ATP hydrolysis, but just how much are we talking? ∆G for the hydrolysis of one mole of ATP into ADP and Pi\text P_i is kcal/mol\text{kcal/mol} ( kJ/mol\text{kJ/mol}) under standard conditions (11 M\text M concentration of all molecules, 2525, and pH=7.0\text{pH} = 7.0). That’s not bad, but things get more impressive under non-standard conditions: ∆G for the hydrolysis of one mole of ATP in a living cell is almost double the value at standard conditions, around 14-14 kcal/mol\text{kcal/mol} ( kJ/mol\text{kJ/mol}).

Reaction coupling

How is the energy released by ATP hydrolysis used to power other reactions in a cell? In most cases, cells use a strategy called reaction coupling, in which an energetically favorable reaction (like ATP hydrolysis) is directly linked with an energetically unfavorable (endergonic) reaction. The linking often happens through a shared intermediate, meaning that a product of one reaction is “picked up” and used as a reactant in the second reaction.
When two reactions are coupled, they can be added together to give an overall reaction, and the ΔG of this reaction will be the sum of the ΔG values of the individual reactions. As long as the overall ΔG is negative, both reactions can take place. Even a very endergonic reaction can occur if it is paired with a very exergonic one (such as hydrolysis of ATP). For instance, we can add up a pair of generic reactions coupled by a shared intermediate, B, as follows2^2:
You might notice that the intermediate, B, doesn't appear in the overall coupled reaction. This is because it appears as a both a product and a reactant, so two Bs cancel each other out when the reactions are added.

ATP in reaction coupling

When reaction coupling involves ATP, the shared intermediate is often a phosphorylated molecule (a molecule to which one of the phosphate groups of ATP has been attached). As an example of how this works, let’s look at the formation of sucrose, or table sugar, from glucose and fructose3,4^{3,4}.

Case study: Let's make sucrose!

The formation of sucrose requires an input of energy: its ΔG is about +27+27 kJ/mol\text{kJ/mol} (under standard conditions). ATP hydrolysis has a ΔG around 30-30 kJ/mol\text{kJ/mol} under standard conditions, so it can release enough energy to “pay” for the synthesis of a sucrose molecule:
How is the energy released in ATP hydrolysis channeled into the production of a sucrose molecule? As it turns out, there are actually two reactions that take place, not just one big reaction, and the product of the first reaction acts as a reactant for the second.
  • In the first reaction, a phosphate group is transferred from ATP to glucose, forming a phosphorylated glucose intermediate (glucose-P). This is an energetically favorable (energy-releasing) reaction because ATP is so unstable, i.e., really "wants" to lose its phosphate group.
  • In the second reaction, the glucose-P intermediate reacts with fructose to form sucrose. Because glucose-P is relatively unstable (thanks to its attached phosphate group), this reaction also releases energy and is spontaneous.
Illustration of reaction coupling using ATP.
In the uncoupled reaction, glucose and fructose combine to form sucrose. This reaction is thermodynamically unfavorable (requires energy).
When this reaction is coupled to ATP hydrolysis, it can take place, occurring in two energetically favorable steps. In the first step, a phosphate group is transferred from ATP to glucose, making the intermediate molecule glucose-P. Glucose-P is reactive (unstable) and can react with fructose to form sucrose, releasing an inorganic phosphate in the process.
This example shows how reaction coupling involving ATP can work through phosphorylation, breaking a reaction down into two energetically favored steps connected by a phosphorylated (phosphate-bearing) intermediate. This strategy is used in many metabolic pathways in the cell, providing a way for the energy released by converting ATP to ADP to drive other reactions forward.

Different types of reaction coupling in the cell

The example above shows how ATP hydrolysis can be coupled to a biosynthetic reaction. However, ATP hydrolysis can also be coupled to other classes of cellular reactions, such as the shape changes of proteins that transport other molecules into or out of the cell.

Case study: Sodium-potassium pump

It’s energetically unfavorable to move sodium (Na+\text {Na}^+) out of, or potassium (K+\text K^+) into, a typical cell, because this movement is against the concentration gradients of the ions. ATP provides energy for the transport of sodium and potassium by way of a membrane-embedded protein called the sodium-potassium pump (Na+/K+ pump).
  1. Three sodium ions bind to the sodium-potassium pump, which is open to the interior of the cell.
  2. The pump hydrolyzes ATP, phosphorylating itself (attaching a phosphate group to itself) and releasing ATP. This phosphorylation event causes a shape change in the pump, in which it closes off on the inside of the cell and opens up to the exterior of the cell. The three sodium ions are released, and two potassium ions bind to the interior of the pump.
  3. The binding of the potassium ions triggers another shape change in the pump, which loses its phosphate group and returns to its inward-facing shape. The potassium ions are released into the interior of the cell, and the pump cycle can begin again.
_Image modified from "The sodium-potassium exchange pump," by Blausen staff (CC BY 3.0)._
In this process, ATP transfers one its phosphate groups to the pump protein, forming ADP and a phosphorylated “intermediate” form of the pump. The phosphorylated pump is unstable in its original conformation (facing the inside of the cell), so it becomes more stable by changing shape, opening towards the outside of the cell and releasing sodium ions outside. When extracellular potassium ions bind to the phosphorylated pump, they trigger the removal of the phosphate group, making the protein unstable in its outward-facing form. The protein will then become more stable by returning to its original shape, releasing the potassium ions inside the cell.
Although this example involves chemical gradients and protein transporters, the basic principle is similar to the sucrose example above. ATP hydrolysis is coupled to a work-requiring (energetically unfavorable) process through formation of an unstable, phosphorylated intermediate, allowing the process to take place in a series of steps that are each energetically favorable.


This article is a modified derivative of “ATP: Adenosine triphosphate,” by OpenStax College, Biology (CC BY 3.0). Download the original article for free at
The modified article is licensed under a CC BY-NC-SA 4.0 license.

Works cited:

  1. Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B. (2011). The regeneration of ATP. In Campbell biology (10th ed., pp. 151). San Francisco, CA: Pearson.
  2. Berg, J. M., Tymoczsko, J. L., and Stryer, L. (2002). A thermodynamically unfavorable reaction can be driven by a favorable reaction. In Biochemistry (5th ed, section 14.1.1). New York, NY: W.H. Freeman. Retrieved from
  3. Singh, N. K. (2007). ATP is the main energy currency in cells. In BIOL 1020 lecture notes: Chapter 8. Retrieved from
  4. Solomon, E., Martin, C., Martin, D., and Berg, L. (2014). ATP donates energy through the transfer of a phosphoric group. In Biology (10th ed., p. 154). Boston, MA: Cengage Learning.

Additional references:

Berg, J. M., Tymoczsko, J. L., and Stryer, L. (2002). Metabolism is composed of many coupled, interconnected reactions. In Biochemistry (5th ed, section 14.1). New York, NY: W.H. Freeman. Retrieved from
Diwan, J. J. (n.d.). Biochemical energetics. In Biochemistry of metabolism. Retrieved from
Jeremy. (2008, March 22). How does ATP couple endergonic and exergonic reactions? Message posted to
Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B. (2011). An introduction to metabolism. In Campbell biology (10th ed., pp. 141-161). San Francisco, CA: Pearson.
Singh, N. K. (2007). Chapter 8. In BIOL 1020 lecture notes. Retrieved from
Solomon, E., Martin, C., Martin, D., and Berg, L. (2014). Energy and metabolism. In Biology (10th ed., pp. 148-164). Boston, MA: Cengage Learning.