Energy coupling & ATP

Which way will a reaction go?

Chemists use free energy (G) to measure the energy in a system that's available to do work. What matters for a reaction is the change, ΔG: the free energy of the products minus that of the reactants.

• If ΔG is negative, the products have less free energy than the reactants. The reaction releases energy and can happen on its own. It's exergonic. Breaking glucose down to CO₂ and water is an example.
• If ΔG is positive, the products have more free energy. The reaction needs an energy input and won't go by itself. It's endergonic. Building proteins from amino acids is an example.

ATP: a molecule built to be broken

ATP (adenosine triphosphate) is made of the base adenine, the sugar ribose and a chain of three phosphate groups. When water splits off the last phosphate, you get ADP (adenosine diphosphate) and inorganic phosphate, written Pᵢ. This is hydrolysis, and it's strongly exergonic.

Under standard conditions, ATP hydrolysis has ΔG°′ = −30.5 kJ/mol. Inside a real cell it releases even more, roughly −50 to −57 kJ/mol, because cells keep the ratio of ATP to ADP far above its equilibrium value, which pushes the reaction harder in the forward direction.

So where does that energy come from? Not from the bond itself. Breaking any bond takes energy; energy is only released when new, more stable bonds form. ATP hydrolysis releases energy overall because ADP + Pᵢ are much more stable than ATP + water:

• The phosphates in ATP are negatively charged and crammed next to each other, so they repel. Splitting one off relieves that strain.
• The freed phosphate can spread its electrons over more arrangements (more resonance), which stabilises it.
• ADP and Pᵢ are surrounded by water molecules more favourably than ATP is (better hydration).

Energy coupling: paying for uphill reactions

Cells constantly need to run endergonic reactions: building molecules, pumping ions, moving muscles. They do it by energy coupling, linking an uphill reaction to a downhill one so that the combined ΔG is negative. ATP hydrolysis is the usual downhill partner.

Coupling isn't just ATP breaking down "nearby" and heat drifting over. If ATP were simply hydrolysed, its energy would be lost as heat. Instead, the two reactions share a chemical step, usually a phosphorylated intermediate: ATP hands its phosphate to one of the reactants, and that phosphorylated molecule is now unstable enough to react.

Here's how the enzyme glutamine synthetase makes the amino acid glutamine, a reaction that's uphill on its own:

1. 1Glutamate + NH₃ → glutamine is endergonic by itself, so it won't happen directly.
2. 2Instead, ATP transfers its end phosphate to glutamate, forming glutamyl phosphate and ADP.
3. 3Glutamyl phosphate is much less stable than glutamate, so it reacts readily with NH₃, forming glutamine and releasing Pᵢ.
4. 4Overall: glutamate + NH₃ + ATP → glutamine + ADP + Pᵢ. The ΔG values of the two parts add up, and the total is negative.

Transport works the same way. The sodium–potassium pump hydrolyses one ATP per cycle and moves 3 Na⁺ out and 2 K⁺ in, both against their gradients. The phosphate is attached to the pump protein itself, and that change of shape is what pushes the ions across.

Currency, not savings

ATP is often called the cell's energy currency, and the word is apt: it's spent almost as soon as it's made. Your body holds only a small amount of ATP at any moment, yet you recycle roughly your own body weight of it every day, so each ATP molecule is rebuilt from ADP around a thousand times daily.

For long-term storage, cells use other molecules: glycogen in animals, starch in plants and, above all, fat. These are broken down when needed, and their energy is used to turn ADP back into ATP. That happens in three main ways: substrate-level phosphorylation (an enzyme moves a phosphate directly from a molecule onto ADP, as in glycolysis), oxidative phosphorylation in mitochondria, and photophosphorylation in chloroplasts.

Redox: energy carried by electrons

Much of the energy in food is moved around not as ATP but as electrons. Losing electrons is oxidation; gaining them is reduction (a memory aid: OIL RIG, oxidation is loss, reduction is gain). The two always happen together, so these are called redox reactions. In biology, electrons often travel with a proton, as a hydrogen atom, so a molecule losing hydrogens is usually being oxidised.

Cells use small carrier molecules to shuttle electrons around:

• NAD⁺ picks up two electrons and a proton to become NADH. It collects electrons from food in glycolysis and the Krebs cycle and delivers them to the electron transport chain.
• FAD picks up two electrons and two protons to become FADH₂, with a similar job.
• NADP⁺ / NADPH is the version cells use for building molecules, for example in the Calvin cycle of photosynthesis.

Electrons release energy as they move from a molecule that holds them loosely to one that pulls on them harder. Oxygen pulls hardest of all. Passing a pair of electrons from NADH all the way to oxygen releases about 220 kJ/mol, several ATPs' worth. Cells don't release it in one burst, which would mostly be lost as heat. The electron transport chain lets it out in small steps that can be captured.

Going further: ΔG in real cells

The standard value ΔG°′ assumes every reactant and product is at 1 M (at pH 7), which never happens in a cell. The actual ΔG depends on the concentrations: ΔG = ΔG°′ + RT ln Q, where Q is the ratio of products to reactants at that moment. Keep products scarce and reactants plentiful, and Q is small, ln Q is negative, and the reaction becomes more favourable. That's why ATP hydrolysis releases about −50 kJ/mol in cells instead of −30.5.

Redox reactions have their own version: ΔG°′ = −nFΔE°′, where n is the number of electrons, F is the Faraday constant (about 96.5 kJ per volt per mole of electrons) and ΔE°′ is the difference in reduction potential between acceptor and donor. For NADH (−0.32 V) giving electrons to O₂ (+0.82 V), ΔE°′ = 1.14 V, so ΔG°′ ≈ −2 × 96.5 × 1.14 ≈ −220 kJ/mol.

Key terms

Free energy change (ΔG)

The difference in usable energy between products and reactants; negative means the reaction can happen on its own.

Exergonic / endergonic

Releases free energy (ΔG < 0) / needs an input of free energy (ΔG > 0).

ATP hydrolysis

ATP + H₂O → ADP + Pᵢ; about −30.5 kJ/mol under standard conditions and about −50 kJ/mol in cells.

Energy coupling

Linking an endergonic reaction to an exergonic one so that their combined ΔG is negative.

Phosphorylated intermediate

A molecule that has been given a phosphate by ATP, making it unstable enough to take part in the next reaction.

Oxidation / reduction

Loss of electrons / gain of electrons; they always occur together in redox reactions.

NAD⁺ / NADH

An electron carrier in its oxidised form / its reduced form, carrying two electrons from food to the electron transport chain.

Substrate-level phosphorylation

Making ATP by transferring a phosphate directly from a substrate molecule to ADP.

Check yourself

Try answering in your head before you open each answer.

• 1.Reaction A has ΔG = +20 kJ/mol and reaction B has ΔG = +45 kJ/mol. Using ATP hydrolysis at −30.5 kJ/mol, which can be driven by one ATP? What could a cell do about the other?Show answerHide

  A can: +20 − 30.5 = −10.5 kJ/mol, which is negative. B can't with one ATP: +45 − 30.5 = +14.5, still positive. The cell could couple B to the hydrolysis of two ATP (or of ATP to AMP + PPᵢ, followed by breaking down the PPᵢ), or keep its products at a very low concentration so the actual ΔG becomes negative.

• 2.A poison stops all ATP production in a cell instantly. Why would the cell run out of usable energy within seconds to minutes, even if it has plenty of glycogen and fat?Show answerHide

  ATP is a currency that's used and rebuilt constantly, and the cell only holds a small amount at a time. Glycogen and fat can't power cell work directly: their energy has to be converted into ATP first. With ATP production blocked, the small existing supply is spent almost immediately.

• 3.In respiration, glucose becomes CO₂ and O₂ becomes H₂O. Which is oxidised and which is reduced? Where does NAD⁺ fit in?Show answerHide

  Glucose is oxidised: it loses electrons (along with hydrogens). O₂ is reduced: it gains electrons and hydrogens to form water. NAD⁺ is the go-between: it's reduced to NADH when it picks up electrons from glucose's breakdown, then oxidised back to NAD⁺ when it hands them to the electron transport chain, which passes them to O₂.