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ATP and reaction coupling

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:
Note: Pi just stands for an inorganic phosphate group (PO43).
Like most chemical reactions, the hydrolysis of ATP to ADP is reversible. The reverse reaction, which regenerates ATP from ADP and Pi, 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.
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:
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 is 7.3 kcal/mol (30.5 kJ/mol) under standard conditions (1 M concentration of all molecules, 25°C, and 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 kcal/mol (57 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:
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.

Case study: Let's make sucrose!

The formation of sucrose requires an input of energy: its ΔG is about +27 kJ/mol (under standard conditions). ATP hydrolysis has a ΔG around 30 kJ/mol under standard conditions, so it can release enough energy to “pay” for the synthesis of a sucrose molecule:
glucose +fructosesucroseΔG=+27 kJ/molATP+H2OADP+PiΔG=30 kJ/molglucose +fructose+ATPsucrose+ADP+PiΔG=3kJ/mol
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+) out of, or potassium (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 of 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.

Want to join the conversation?

  • piceratops ultimate style avatar for user tmollman
    Is it possible to run out of ATP?
    (32 votes)
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    • aqualine ultimate style avatar for user Lydia
      The cell also has in place mechanisms to stop this from happening. Like the enzyme phosphofructokinase (crazy name, I know) which is involved in the beginnings of glycolysis. Glycolysis is one of the early stages of making ATP from ADP. So, when there's more ADP around phosphofructokinase will work harder (which allows to the whole cycle to go faster, regenerating more ATP). When there's a lot of ATP, though, phosphofructokinase (and other enzymes like it) will slow down. So basically, the cell has things set up carefully so that the right amount of ATP will be available (unless, as Laurent said, the cell is dying).
      (62 votes)
  • leafers seed style avatar for user fukushima.vitor
    What happens with those -3kJ/mol from the formation of sucrose? Does it transform on heat?
    (32 votes)
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  • blobby green style avatar for user Autumn Bedillion
    Where does the energy come from to synthesis ATP from ADP and P ?
    is it when you couple the reaction that turns it back into ATP
    (14 votes)
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  • blobby green style avatar for user noorshom
    Why just ATP though? Why not TTP, CTP, or GTP as well? If it is possible with one nucleotide, why not the others?
    (13 votes)
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  • primosaur ultimate style avatar for user Izabela Muller
    Why do energy released by ATP under standard conditions at 25 °C is important if human body temperature is 36.5–37.5 °C ?
    (6 votes)
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  • blobby green style avatar for user 54239
    If the production of ATP and the hydrolysis of ADP and Pi is cyclic, why do we run out of ATP and require glycolysis for ATP production? Wouldn't the ATP simply be recyclable and neverending?
    (5 votes)
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  • starky ultimate style avatar for user Greacus
    Wouldn't ATP be more stable when the middle phosphates' charged oxygen was located above the phosphates, so the charges are further apart?
    (2 votes)
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    • starky ultimate style avatar for user Sean Kilfoy
      Single bonds rotate along their axis, so any drawing you might see of a molecule is, by all means, NOT set in stone. Yes, like charges move away from each other, when permitted, but we usually don't draw it like that, for the sake of consistency.
      (4 votes)
  • blobby green style avatar for user abdullahzamel2
    When it is said "ATP releases energy", I would imagine something imaginary (kinda like a wave) travelling to help in creating another bond.

    Energy is not created nor destroyed. At the end of the reaction above:
    3K. energy transferred as heat.

    The reaction glucose + fructose requires 27K.
    As I said I used to imagine some imaginary wave, instead I'm thinking now that when ATP gives this 27K. it does this by creating instability, and we classify it as giving energy. Is this true?

    If true, then theoretically can't phosphate, without being part of ATP, just 'run' around the cell and just keep creating instability (sounds like unlimited free energy). Why does it have to be reattached to ADP to form ATP again? Is it because inorganic phosphate is not unstable enough?

    If not true then what is this 27K. energy represented by?
    (2 votes)
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    • piceratops ultimate style avatar for user RowanH
      It is not ATP itself that releases energy, and also not the bond to the final phosphate bond being broken. If you think about it, you actually need energy to break any bonds, including that one (otherwise it would fall appart and not be a bond that keeps atoms together!). The energy is actually from hydrolyising ATP, ie breaking that bond, but also forming new ones. The products ADP and inorganic phosphate are lower in (potential) energy than ATP. (This has several reasons, and isn't as simple as counting bonds and expecting them to have the same energies as in other molecules, but also that having a solvated inorganic phosphate is more entropically favourable). So, the ATP reaction wants to move in the ADP+ Pi direction. But you can't just do that and hope it magically drives another reaction in reverse/uphill. What often happens, is that ATP will react with the reactants of the other reaction, some steps occur converting reactant to product, and in the end ADP and Pi are released. Each step turns out energetically favourable, driven forward by a loss in free energy, and by the end you have converted reactants to products in a reaction that would not normally go forwards on its own by allowing ATP to drop from a high energy to low energy. Does this help explain?
      (5 votes)
  • leafers ultimate style avatar for user manderZ D
    Could someone explain what "ΔG" is? I know it means something like "free energy", but I can't find any good articles about what it really is.
    (1 vote)
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  • blobby green style avatar for user noarafaeli06
    Does it release heat energy?
    (3 votes)
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