In this article we will discuss about the importance of ATP and other compounds of high energy potential.
Living cells must perform some endergonic reactions; these are not only anabolic reactions like those already mentioned (biosynthesis of macro- molecules such as polysaccharides, proteins, nucleic acids), but also some reactions of transport, transmission, mechanical work, functioning of the nervous system, catabolic reactions, particularly when the substrates must be activated before they can be degraded (e.g., activation of fatty acids, phosphorylation of sugars).
The energy required is supplied by the exergonic reactions thanks to energetic coupling. This energetic coupling is one of the important characteristics of living beings.
On the one hand, it implies that the exergonic reaction which supplies the energy must have a negative ∆G’ greater in absolute value than the positive ∆G’ of the endergonic reaction to which it is coupled. On the other hand, the two coupled reactions must have a common intermediate.
Let us consider two reactions having the common intermediate B:
(i) Endergonic reaction A ←→ B, ∆G0 = + 1362 cal/mole, K = 0.1
(ii) Exergonic reaction B ←→ C, ∆G0 = – 4 086 cal/mole, K = 1 000
(iii) Overall reaction A ←→ C, ∆G0 = -2 724 cal/mole, equilibrium constant K = 1000 x 0.1 = 100
If one starts with 1011 moles of A, the equilibrium of the first reaction ought to be attained when 10% of the molecules are transformed, i.e. when 101 moles of A are converted to 101 moles of B. But as soon as the product B appears, the second reaction can take place, and here for equilibrium, 99.9% of moles of B must be transformed into C.
In the final equilibrium, there will be 10 moles of A, 1 of B and 1 000 of C (which is in conformity with the equilibrium constants of the 2 reactions, 0.1 and 1 000 respectively); in other words 99% (1 000/1 011) of the moles of A present at the start will have been transformed into C. This shows that the coupling of the 2 reactions has enabled the exergonic reaction to “carry along” the endergonic reaction so that there remains only 1% of the molecules of A present initially.
The coupling results from the equilibrium constants of the 2 reactions having in common the substance B, and the process can, for example, be started in living cells when the concentration of A increases or when that of C decreases.
It is clear that it would be extremely advantageous for the cells to have a single common intermediate compound, formed in all exergonic reactions and usable by all endergonic reactions; in fact such a compound exists: it is ATP.
1. ATP:
Adenosine-triphosphate or ATP, the structure of which is shown in figure 3-2, has 3 O-P bonds;
— due to rearrangements in electron distribution and a greater stability of the products formed — is accompanied by a strong liberation of utilizable energy, i.e. a standard free enthalpy change ∆G0# -7 kcal/mole in one of the following two reactions:
ADP + H2O → AMP + Pi + H+
ATP + H2O → ADP + Pi + H+
This second type of link is sometimes represented by a squiggle as may be seen in figure 3-2, and called “energy-rich bond”, a denomination which is not quite correct because it is the energy liberated by the hydrolysis which is high and not the energy of the bond. It is also said sometimes that ATP (as also the other compounds indicated below) is an “energy-rich” compound.
Actually, upon complete oxidation into CO2 + H2O, glucose can liberate a much larger quantity of energy (as mentioned earlier, oxidation of one molecule of glucose can yield 686 kcal, whereas the transformation of ATP into ADP + Pi yields only 7 kcal), but the superiority of ATP resides in the fact that — contrary to glucose — it can participate directly in energy transfer reactions.
It is more correct to state that ATP has a high energy potential or a high phosphate group transfer potential, which explains the fact that its terminal phosphate group can be easily transferred to another compound (glucose, for example), thanks to the energy which is made available by the hydrolysis of ATP into ADP + P, and which is immediately utilizable for the phosphorylation of glucose (an endergonic reaction).
It must be noted that the quantity of energy available varies according to the conditions and particularly as a function of the respective concentrations of the reactants, which come into play whenever the conditions are other than standard (i.e. always in living cells) and therefore, the values of ∆G will be more or less remote from ∆G0.
Moreover, all the energy made available is not necessarily transferred entirely inside the system formed by 2 coupled reactions; if only a part of this energy is utilized, the rest can be transformed into thermal energy.
ATP occupies a place of prime importance in processes of energy transfer. As stated below, the reactions which supply energy after absorption of light or oxidation of glucose lead to the formation of ATP from ADP + Pi, while the reactions requiring energy are linked either with the hydrolysis of ATP to ADP + Pi (even if the latter appears only subsequently in the form of free or- thophosphate), or with the hydrolysis of another compound of high energy potential (see Table).
Very often indeed, the formation of this other compound is itself linked with the hydrolysis of ATP as, for example, in the case of the UTP required for the synthesis of polysaccharides (see figs. 4-22 and 4-23), the CTP required for the synthesis of phospholipids, the GTP required for the biosynthesis of proteins or the ribo- and deoxyribonucleosides-triphosphates required for the biosynthesis of the RNAs and DNAs.
To illustrate the manner in which ATP enables a “chemical work” i.e. an endergonic reaction to take place, let us take a simple example: the condensation of one molecule of glucose and one molecule of fructose to form one molecule of sucrose (for structures see figure 4-17):
The energy required for this reaction is supplied by the hydrolysis of ATP, an exergonic reaction already indicated above:
In reality the 2 reactions are not independent as written above; they are coupled as follows:
One may note that there are 2 intermediates common to the 3 coupled reactions: glucose-6-phosphate for the 1st and 2nd reactions, glucose-1-phosphate for the 2nd and 3rd reactions, in the first reaction a part of the energy of ATP has been transferred to glucose together with the phosphate group; this enables glucose-1-phosphate to react with fructose. The loss of free energy is 1.5 kcal/mole (which may be dissipated in the form of heat) and it can be said that for these 3 coupled reactions the efficiency of energy storage is 5.5 X 100/7 # 80%.
Generally, as shown by figure 3-3, the energy — originating from various sources which are not all listed in the diagram — is transferred to ADP + P, to form ATP. Energy is then transferred to other processes from ATP which splits into ADP + Pi.
The cleavage of ATP into ADP + Pi with liberation of energy is the most frequent reaction, but it is not the only one involving ATP.
The latter can transfer:
1. An orthophosphate group (with release of adenosine-5′-diphosphate or ADP) for example to an alcoholic hydroxyl; these transfers are catalyzed by kinases, and the reaction is reversible only if the energy potential of the compound formed is comparable with that of ATP; otherwise ATP will be regenerated from ADP by another reaction;
2. A pyrophosphate group (with release of adenosine-5′-monophosphate or AMP) for example during the formation of 5-phosphoribosyl-1-pyrophos- phate from ribose-5-phosphate (see fig. 6-18);
3. An AMP group (with release of pyrophosphate) for example during the activation of fatty acids (see fig. 5-10) or amino acids (see fig. 6-39);
4. An adenosyl group (with release of orthophosphate and pyrophosphate), for example during the formation of S-adenosyl-methionine, a coenzyme (see fig. 2-20).
2. Other Compounds of High Energy Potential:
Among these compounds, some have a phosphate group (designated by the symbol℗). Although the ∆G’ corresponding to the hydrolysis is rather strongly negative, the hydrolysis of these compounds is not necessarily rapid in aqueous medium and for it to take place with appreciable velocity it must, in most cases, be catalyzed by a specific enzyme.
The principal compounds of high energetic potential are represented in the Table. (The linkage, the hydrolysis of which is accompanied by the liberation of a large quantity of energy is designated by the symbol ~).
Phosphocreatine (or creatine-phosphate) in Vertebrates and phosphoarginine in Invertebrates are reserves of phosphates of high energetic potential, hence the name “phosphagens” given to these compounds; an energetic coupling:
brings about the storage reaction (ATP + Creatine —> ADP + Phosphocreatine) when ATP is present in excess and inversely, the formation of ATP by the reverse reaction (see fig. 7-13) when the cell needs ATP.
We must now consider the origin of these compounds of high energetic potential; most of them are formed from ATP by a coupling similar to the one we have just seen for the formation of phosphocreatine; the problem is therefore the determination of the origin of ATP.
ATP is formed in living organisms by phosphorylation of ADP coupled with oxidation reactions which are accompanied by a large decrease of free energy and which therefore supply the energy needed.
We will study the phosphorylations which take place during transfers of electrons in the respiratory chain in aerobic cells (where oxygen is the final electron acceptor, i.e. the oxidant of nutritive substances) and during the light phase of photosynthesis (which enables the conversion of energy of light into chemical energy); these two processes are somewhat similar and both of them take place in cellular organelles: the mitochondria and the chloroplasts respectively; we will also study the phosphorylation of ADP into ATP in anaerobic cells (where the electrons cannot reach oxygen).