Basic concepts in bioenergetics: phosphoryl group transfers and ATP hydrolysis

Adenosine $5$‍’-triphosphate (ATP) serves as the main source of free energy in living cells. The energy stored by ATP can be liberated through direct hydrolysis or by group transfer.

Figure 1. Molecular structure of ATP, ADP, and AMP.

Direct hydrolysis of ATP consists of nucleophilic attack by ${\text{H}}_2\text{O}$‍ at the $\gamma$‍ phosphate position of ATP and cleavage of the $\gamma -\beta$‍ phosphoanhydride bond:

Direct hydrolysis of ATP liberates energy mainly in the form of heat. This heat energy can be used to cycle proteins through different conformations (for instance, in muscle contraction).

Group transfer reactions involve the covalent transfer of a portion of the ATP molecule to a substrate (e.g. an enzyme active site), which in turn makes subsequent metabolic reactions involving this substrate more thermodynamically favorable. Table 1 classifies the three group transfer reactions that involve ATP by the phosphate position of ATP at which nucleophilic attack occurs.

Adenylyl transfer has the largest negative standard free energy change, and is commonly coupled to biological reactions that have a particularly large positive standard free energy change. One example is fatty acid adenylylation, in which exergonic adenylylation of fatty acid (initiating by nucleophilic attack by the carboxylate ion of the fatty acid) and pyrophosphatase-catalyzed pyrophosphate hydrolyzation is coupled to endergonic condensation of fatty acid and coenzyme A, yielding fatty acyl-coA, AMP, and two inorganic phosphate molecules: