MCAT Biochemistry Review

Chapter 12: Bioenergetics and Regulation of Metabolism

12.2 The Role of ATP

The human body can make use of different energy sources with roughly the same efficiency, but all nutrient molecules are not created equally. For example, fats are much more energy-rich than carbohydrates, proteins, or ketones. Complete combustion of fat results in  of energy, compared with only  derived from carbohydrates, proteins, or ketones. Because fats are so much more energy-dense than other biomolecules, they are preferred for long-term energy storage. Think of the difference between fats and carbohydrates like the difference between a 16 GB and an 8 GB storage drive. The storage drive with a greater capacity occupies the same amount of physical space, but holds twice as much data. While different energy sources provide greater or lesser caloric values, the end goal is to have energy in a readily available form. For the cell, this isadenosine triphosphate (ATP), shown in Figure 12.1.

Figure 12.1. Adenosine Triphosphate (ATP)


ATP is the major energy currency in the body. It is a mid-level energy carrier, as seen in Table 12.1, and is formed from substrate-level phosphorylation as well as oxidative phosphorylation. Why do we want ATP to be a mid-level carrier and not a higher-level one? Think about your wallet. If you never had the ability to get change back after a purchase, what type of bill would you want in abundance? One dollar bills! Similarly, ATP cannot get back the “leftover” free energy after a reaction, so it's best to use a carrier with a smaller free energy. ATP provides about of energy under physiological conditions. If a reaction only requires  to overcome a positive ΔG value, then  have been wasted. The waste would be even higher with a higher-energy compound like creatine phosphate.





Second messenger

Creatine phosphate


Direct phosphorylation in muscle



Energy turnover in all cell types

Glucose 6-phosphate


Intermediate of glycolysis and gluconeogenesis



ATP synthesis

Table 12.1. Free Energy of Hydrolysis for Key Metabolic Phosphate Compounds

Remember that most of the ATP in a cell is produced by mitochondrial ATP synthase, as described in Chapter 10 of MCAT Biochemistry Review, but some ATP is produced during glycolysis and the citric acid cycle. ATP consists of an adenosine molecule attached to three phosphate groups, and is generated from ADP and Pi with energy input from an exergonic reaction or electrochemical gradient. ATP is consumed either through hydrolysis or the transfer of a phosphate group to another molecule. If one phosphate group is removed, adenosine diphosphate (ADP) is produced; if two phosphate groups are removed, adenosine monophosphate (AMP) is the result. In a single day, an average-sized person uses about 90 percent of her weight in ATP but only has about 50 grams of ATP available at any given time. Continuous recycling of ATP, ADP, and Pimore than 1000 times per day accounts for this discrepancy.

What makes ATP such a good energy carrier is its high-energy phosphate bonds. The negative charges on the phosphate groups experience repulsive forces with one another, and the ADP and Pi molecules that form after hydrolysis are stabilized by resonance. While ATP doesn't rapidly break down on its own in the cell, it is much more stable after hydrolysis. This accounts for the very negative value of ΔG. Under standard conditions ΔG° is about  At pH 7 and with excess magnesium, the standard free energy change is still . ADP, which also displays charge repulsion and resonance stabilization after hydrolysis, has similar ΔG values, but AMP has a much smaller ΔG° near .


ATP hydrolysis is most likely to be encountered in the context of coupled reactions. Many coupled reactions use ATP as an energy source. For example, the movement of sodium and potassium against their electrochemical gradients requires energy, which is harnessed from the hydrolysis of ATP.

ATP cleavage is the transfer of a high-energy phosphate group from ATP to another molecule. Generally, this activates or inactivates the target molecule. With these phosphoryl group transfers, the overall free energy of the reaction will be determined by taking the sum of the free energies of the individual reactions.


ATP is used to fuel energetically unfavorable reactions or to activate or inactivate other molecules.


ATP can provide a phosphate group as a reactant. For example, in the phosphorylation of glucose in the early stages of glycolysis, ATP donates a phosphate group to glucose to form glucose 6-phosphate. The information in Table 12.1 indicates the free energy of hydrolysis, which can be conceptualized as the transfer of the phosphate group to water. To determine the free energy of phosphoryl group transfer to another biological molecule, one could use Hess's law and calculate the difference in free energy between the reactants and products:

(reverse reaction from Table 12.1)


Hess's law, discussed in Chapter 7 of MCAT General Chemistry Review, applies for all of the state functions, including pressure, density, temperature, volume, enthalpy, internal energy, free energy, and entropy.

MCAT Concept Check 12.2:

Before you move on, assess your understanding of the material with these questions.

1.    How does coupling with ATP hydrolysis alter the energetics of a reaction?

2.    Explain why ATP is an inefficient molecule for long-term energy storage.

3.    Using Table 12.1, calculate the free energy change for the synthesis of ATP from cAMP and inorganic phosphate. Note: cAMP is hydrolyzed to AMP, and the free energy of hydrolysis for ATP and ADP is approximately equal.