Having developed some fundamental principles of energy changes in chemical systems and reviewed the common classes of reactions, we can now examine the energy cycle in cells and the special role of ATP as the energy currency that links catabolism and anabolism. Heterotrophic cells obtain free energy in a chemical form by the catabolism of nutrient molecules, and they use that energy to make ATP from ADP and Pi .

ATP then donates some of its chemical energy to endergonic processes such as the synthesis of metabolic intermediates and macromolecules from smaller precursors, the transport of substances across membranes against concentration gradients, and mechanical motion. This donation of energy from ATP is refer to as coupled reaction which generally involves the covalent participation of ATP in the reaction that is to be driven, with the eventual result that ATP is converted to ADP and Pi or, in some reactions, to AMP and 2 Pi . We discuss here the chemical basis for the large free-energy changes that accompany hydrolysis of ATP and other high-energy phosphate compounds, and we show that most cases of energy donation by ATP involve group transfer, not simple hydrolysis of ATP. To illustrate the range of energy transductions in which ATP provides the energy.



The hydrolytic cleavage of the terminal phosphoric acid anhydride (phosphoanhydride) bond in ATP separates one of the three negatively charged phosphates and thus relieves some of the internal electrostatic repulsion in ATP; the Pi released is stabilized by the formation of several resonance forms not possible in ATP.

The free-energy change for ATP hydrolysis is −30.5 kJ/mol under standard conditions, but the actual free energy of hydrolysis (ΔG) of ATP in living cells is very different: the cellular concentrations of ATP, ADP, and Pi are not identical and are much lower than the 1.0 M of standard conditions. Furthermore, Mg 2+ in the cytosol binds to ATP and ADP, and for most enzymatic reactions that involve ATP as phosphoryl group donor, the true substrate is MgATP 2+ . The relevant ΔG′° is therefore that for MgATP 2+ hydrolysis. We can calculate ΔG for ATP hydrolysis using data such as those in Table. The actual free energy of hydrolysis of ATP under intracellular conditions is often called its phosphorylation potential, ΔGp.

FIGURE DEPICTING- Energy changes associated with ATP hydrolysis.
FIGURE DEPICTING :- Energy changes associated with ATP hydrolysis.

Because the concentrations of ATP, ADP, and Pi differ from one cell type to another, ΔGp for ATP likewise differs among cells. Moreover, in any given cell, ΔGp can vary from time to time, depending on the metabolic conditions and how they influence the concentrations of ATP, ADP, Pi , and H+ (pH). We can calculate the actual free-energy change for any given metabolic reaction as it occurs in a cell, providing we know the concentrations of all the reactants and products and other factors (such as pH, temperature, and [Mg 2+ ]) that may affect the actual free-energy change.


  • Phosphoenolpyruvate (PEP)  contains a phosphate ester bond that undergoes hydrolysis to yield the enol form of pyruvate, and this direct product can tautomerize to the more stable keto form. Because the reactant (PEP) has only one form (enol) and the product (pyruvate) has two possible forms, the product is stabilized relative to the reactant. This is the greatest contributing factor to the high standard free energy of hydrolysis of phosphoenolpyruvate: ΔG′° = −61.9 kJ/mol.
FIGUR E DEPICTING -Hydrolysis of phosphoenolpyruvate (PEP).
FIGUR E DEPICTING :- Hydrolysis of phosphoenolpyruvate (PEP)
  • Another three-carbon compound, 1,3-bisphosphoglycerate, contains an anhydride bond between the C-1 carboxyl group and phosphoric acid. Hydrolysis of this acyl phosphate is accompanied by a large, negative, standard free-energy change (ΔG′° = −49.3 kJ/mol), which can, again, be explained in terms of the structure of reactant and products. When H2O is added across the anhydride bond of 1,3-bisphosphoglycerate, one of the direct products, 3-phosphoglyceric acid, can lose a proton to give the carboxylate ion, 3-phosphoglycerate, which has two equally probable resonance forms. Removal of the direct product (3- phosphoglyceric acid) and formation of the resonance-stabilized ion favor the forward reaction.
FIGURE DEPICTING - Hydrolysis of 1,3-bisphosphoglycerate.
FIGURE DEPICTING - Hydrolysis of 1,3-bisphosphoglycerate
  • In phosphocreatine, the P—N bond can be hydrolyzed to generate free creatine and Pi . The release of Pi and the resonance stabilization of creatine favor the forward reaction. The standard free-energy change of phosphocreatine hydrolysis is again large, −43.0 kJ/mol.

FIGURE DEPICTING -Hydrolysis of phosphocreatine.
FIGURE DEPICTING - Hydrolysis of phosphocreatine
  • Thioesters, in which a sulfur atom replaces the usual oxygen in the ester bond, also have large, negative, standard free energies of hydrolysis. Acetyl- coenzyme A, or acetyl-CoA , is one of many thioesters important in metabolism. The acyl group in these compounds is activated for transacylation, condensation, or oxidation-reduction reactions. Thioesters undergo much less resonance stabilization than do oxygen esters; consequently, the difference in free energy between the reactant and its hydrolysis products, which are resonance-stabilized, is greater for thioesters than for comparable oxygen esters (Fig. 13-17). In both cases, hydrolysis of the ester generates a carboxylic acid, which can ionize and assume several resonance forms. Together, these factors result in the large, negative ΔG′° (−31.4 kJ/mol) for acetyl-CoA hydrolysis.

FIGURE DEPICTING-Hydrolysis of acetyl-coenzyme A.
FIGURE DEPICTING-Hydrolysis of acetyl-coenzyme A


  • When simple precursors are assembled into high molecular weight polymers with defined sequences (DNA, RNA, proteins), energy is required both for the condensation of monomeric units and for the creation of ordered sequences. The precursors for DNA and RNA synthesis are nucleoside triphosphates, and polymerization is accompanied by cleavage of the phosphoanhydride linkage between the α and β phosphates, with the release of PPi. The moieties transferred to the growing polymer in these reactions are adenylate (AMP), guanylate (GMP), cytidylate (CMP), or uridylate (UMP) for RNA synthesis, and their deoxy analogs (with TMP in place of UMP) for DNA synthesis. As noted above, the activation of amino acids for protein synthesis involves the donation of adenylyl groups from ATP that several steps of protein synthesis on the ribosome are also accompanied by GTP hydrolysis. In all these cases, the exergonic breakdown of a nucleoside triphosphate is coupled to the endergonic process of synthesizing a polymer of a specific sequence


  • ATP can supply the energy for transporting an ion or a molecule across a membrane into another aqueous compartment where its concentration is higher. Transport processes are major consumers of energy; in human kidney and brain, for example, as much as two-thirds of the energy consumed at rest is used to pump Na + and K+ across plasma membranes via the Na + K+ ATPase.
  • The transport of Na + and K+ is driven by cyclic phosphorylation and dephosphorylation of the transporter protein, with ATP as the phosphoryl group donor. Na + -dependent phosphorylation of the Na + K+ ATPase forces a change in the protein’s conformation, and K+ -dependent dephosphorylation favors return to the original conformation. Each cycle in the transport process results in the conversion of ATP to ADP and Pi , and it is the free-energy change of ATP hydrolysis that drives the cyclic changes in protein conformation that result in the electrogenic pumping of Na + and K+ . Note that in this case, ATP interacts covalently by phosphoryl group transfer to the enzyme, not to the substrate.
  • In the contractile system of skeletal muscle cells, myosin and actin are specialized to transduce the chemical energy of ATP into motion. ATP binds tightly but noncovalently to one conformation of myosin, holding the protein in that conformation. When myosin catalyzes the hydrolysis of its bound ATP, the ADP and Pi dissociate from the protein, allowing it to relax into a second conformation until another molecule of ATP binds.
  • The binding and subsequent hydrolysis of ATP (by myosin ATPase) provide the energy that forces cyclic changes in the conformation of the myosin head. The change in conformation of many individual myosin molecules results in the sliding of myosin fibrils along actin filaments, which translates into macroscopic contraction of the muscle fiber.


  • ATP is the primary high-energy phosphate compound produced by catabolism, in the processes of glycolysis, oxidative phosphorylation, and, in photosynthetic cells, photophosphorylation.


This reaction is fully reversible, so, after the intense demand for ATP ends, the enzyme can recycle AMP by converting it to ADP, which can then be phosphorylated to ATP in mitochondria. A similar enzyme, guanylate kinase, converts GMP to GDP at the expense of ATP. By pathways such as these, energy conserved in the catabolic production of ATP is used to supply the cell with all required NTPs and dNTPs.

Phosphocreatine, also called creatine phosphate, serves as a ready source of phosphoryl groups for the quick synthesis of ATP from ADP. The PCr concentration in skeletal muscle is approximately 30 mM, nearly 10 times the concentration of ATP, and in other tissues such as smooth muscle, brain, and kidney, [PCr] is 5 to 10 mM. The enzyme creatine kinase catalyzes the reversible reaction When a sudden demand for energy depletes ATP, the PCr reservoir is used to replenish ATP at a rate considerably faster than ATP can be synthesized by catabolic pathways. When the demand for energy slackens, ATP produced by catabolism is used to replenish the PCr reservoir by reversal of the creatine kinase reaction.


Inorganic polyphosphate, denoted by polyP (or (polyP)n , where n is the number of orthophosphate residues), is a linear polymer composed of many tens or hundreds of Pi residues linked through phosphoanhydride bonds. This polymer, present in all organisms, may accumulate to high levels in some cells. One potential role for polyP is to serve as a phosphagen, a reservoir of phosphoryl groups that can be used to generate ATP, in the same way that creatine phosphate is used in muscle. PolyP has about the same phosphoryl group transfer potential as PPi . The shortest polyphosphate, PPi (n = 2),


  • ATP is the chemical link between catabolism and anabolism. It is the energy currency of the living cell. The exergonic conversion of ATP to ADP and Pi , or to AMP and PPi , is coupled to many endergonic reactions and processes.
  • Direct hydrolysis of ATP is the source of energy in some processes driven by conformational changes but, in general, it is not ATP hydrolysis but the transfer of a phosphoryl, pyrophosphoryl, or adenylyl group from ATP to a substrate or enzyme that couples the energy of ATP breakdown to endergonic transformations of substrates.
  • Through these group transfer reactions, ATP provides the energy for anabolic reactions, including the synthesis of informational macromolecules, and for the transport of molecules and ions across membranes against concentration gradients and electrical potential gradients.
  • To maintain its high group transfer potential, ATP concentration must be held far above the equilibrium concentration by energy-yielding reactions of catabolism.
  • Cells contain other metabolites with large, negative, free energies of hydrolysis, including phosphoenolpyruvate, 1,3-bisphosphoglycerate, and phosphocreatine. These high-energy compounds, like ATP, have a high phosphoryl group transfer potential. Thioesters also have high free energies of hydrolysis.
  • Inorganic polyphosphate, present in all cells, may serve as a reservoir of phosphoryl groups with high group transfer potential.


  • Lehninger  principles of biochemistry seventh edition By  David L. Nelson and Michael M. Cox
  • voets and voets biochemistry 4th edition
  • Life sciences  fundamental and practices sixth edition, pathfinder publication By Pranav Kumar and Usha Mina
  • Essential cell biology (fourth edition) by ALBERTS, BRAY, HOPKIN, JOHNSON, LEWIS, RAFF, ROBERTS, WALTER

:- Article Written By Zahra Madraswala


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