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Thursday, September 04, 2008

Why Is ATP an Important Energy Currency in Biochemistry?

For many years the answer to this question seemd obvious. As described by Fritz Lipmann, ATP has "high energy" bonds. When these bonds are cleaved by hydrolysis a large amount of free energy is released and this energy can be captured and used to perform useful work.

By the mid-1960s this concept was being challenged by biochemists with a deeper appreciation of thermodynamics and chemistry. For example, Albert Lehninger1 wrote in Bioenergetics (1965).
The High-Energy Phosphate Bond—a Misnomer

Those phosphorylated compounds having a relatively high free energy of hydrolysis, such as ATP, phosphocreatine, and phosphopyruvate, are often spoken of as having high-energy phosphate bonds, and such bonds are universally designated by the symbol ~P. These expressions have been very useful and handy to biochemists, but they can be very misleading to the beginner. The term "high-energy phosphate bond" is an unfortunate misnomer because it implies that the energy spoken of is in the bonds and that when the bond is split, energy is set free. This is quite wrong. In the ordinary usage of physical chemistry, bond energy is defined as the energy required to break a given bond between two atoms. Actually relatively enormous energies are required to break chemical bonds, which would not exist if they were not stable. The term "phosphate bond energy" thus does not refer to the true bond energy of the covalent linkages between the phosphorus atom and the oxygen or nitrogen atom. The term "high energy phosphate bond" means only that the difference in energy content between the reactants and the products of hydrolysis is relatively high: the free energy of hydrolysis is not localized in the actual chemical bond itself. It is regrettable that this use of these terms is so deeply ingrained by long usage, but it will not matter if we keep this true meaning in mind.
Lehninger goes on to explain why the standard Gibbs free energy of ATP hydrolysis is such a large negative number. His version is out-of-date so I'll give the modern view from a textbook that I'm very familiar with2 ...

We're discussing the following reaction

ATP + H2O → ADP + Pi          ΔG°′ = -32 kJ mol-1
Several factors contribute to the large amount of energy released during hydrolysis of the phosphoanhydride linkages of ATP.
  1. Electrostatic repulsion among the negatively charged oxygen atoms of the phosphoanhydride groups of ATP is less after hydrolysis. (In cells, ΔG°′hydrolysis is actually increased [made more positive] by the presence of Mg2+ which partially neutralizes the charges on the oxygen atoms of ATP and diminishes electrostatic repulsion.)
  2. The products of hydrolysis, ADP and inorganic phosphate, or AMP and inorganic pyrophosphate, are better solvated than ATP itself. When ions are solvated, they are electrically shielded from each other. The decrease in the repulsion between phosphate groups helps drive hydrolysis.
  3. The products of hydrolysis are more stable than ATP. The electrons on terminal oxygen atoms are more delocalized than those on bridging oxygen atoms. Hydrolysis of ATP replaces one bridging oxygen atom with two new terminal oxygen atoms.
The three contributions are: electrostatic repulsion; solvation effects; and resonance stabilization. The one most responsible for the large negative Gibbs free energy change is the solvation effect. The energies of solvation of ADP and inorganic phosphate are much greater than that of ATP, making hydrolysis to its products a more favorable state.

UPDATE:Under standard conditions the concentrations of substrates and products are equal (1M). Under those conditions, the reaction will proceed to the right until the concentration of ADP is very much higher than that of ATP. When the reaction reaches equilibrium the rates of the forward and reverse reactions are equal and ΔG = 0. At that point, there is no net free energy gain from hydrolysis of ATP. The only reason ATP is an energy currency inside cells is because the system is maintained (regulated) far from equilibrium. In fact, the concentration of ATP inside cells is higher than than that of ADP and the actual free energy change is even more negative than -32 kJ mol-1 [see The Demise of the Squiggle].

1. See Good Science Writers: Albert Lehninger.

2. Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)


Mike said...

I remember this being discussed in my third year physical chemistry class; the professor asked people to put up their hands in support of (or against) the bond breaking required for hydrolysis of ATP to ADP releases energy. The vast majority of the class, including me, put up their hands in support of this statement.

I've never forgotten how wrong I was. Breaking bonds ALWAYS requires energy.

Anonymous said...

Thanks for this post...I actually managed to graduate with a B.S. in Biochemistry without really grasping the difference in language used by physical chemists and biochemists. I understood where the energy came from...I guess I just hadn't internalized it completely.

Penrodyn said...

I remember discussing this with my chemistry teacher in High school in 1978. The problem was, in biology class we were taught all about high energy bonds, while in chemistry class we were taught about how it took energy to break bonds. And so we had a problem, thankfully my excellent chemistry teacher, Gareth Lloyd, put us right. Ever since then I've realized the importance of physical chemistry.