ATP and other energetic molecules

Categories: Cellular biology; physiology

ATP (adenosine triphosphate) is the principal energy carrier for most life processes, including those carried out within plant cells, including the chemical reactions of photosynthesis. The central importance of common intermediates (energy-transferring compounds) is evident in the effects of various chemicals that prevent ATP synthesis. For example, in cells that require oxygen, ATP synthesis is coupled to the oxidation of food-related molecules. Cyanide and carbon monoxide interfere with such cellular oxidations and, therefore, completely prevent the ATP synthesis that is coupled to them. Thus, these compounds are extremely toxic, and cells are often killed by them in a matter of seconds.

Free Energy

Many biological processes require energy in order to occur; that is, they are not by themselves spontaneous. Examples of energy-requiring processes include contraction of muscle, beating of cilia, emission of light by fireflies, heat production by birds and mammals, and establishment of a voltage difference across a cellular membrane. The synthesis of proteins from their constituent amino acids, the formation of complex membrane fats, and, indeed, the synthesis of many other chemical compounds are not themselves spontaneous and, hence, require energy. Energy-dependent processes and reactions are referred to as endergonic.

On the other hand, many processes in organisms are spontaneous and do occur without any other energy source. Most of these are chemical reactions, and all such reactions, being spontaneous, can serve as energy producers. For this reason, they are often called exergonic. They can, in principle, provide energy for events, such as the secretion of nectar or aromatic oils by flower cells, that require it. The form of that energy is free energy.

There is a change in free energy, measured in units of calories or joules, associated with any chemical reaction or physical event. If the change in free energy is more than zero, the process requires energy to proceed; if less than zero, it yields energy and is spontaneous. Thus, the numerical value for the change in free energy of a reaction is very useful for predicting whether it can occur.

The other important aspect of free energy is that its numerical value can be altered by changing the concentrations of the chemicals reacting or the product formed when the chemicals react. For example, consider a hypothetical biochemical reaction in which A is the reactant and B is the product. Imagine that this reaction is not spontaneous; therefore, its free energy change is greater than zero, and it does not “go.” Yet, though A becoming B is not spontaneous, its reverse, B becoming A, is. In other words, if a reaction in one direction has a change in free energy greater than zero, the reverse reaction will have one less than zero. Most important, if a reaction in a particular direction is not spontaneous, it can be made to “go” anyway, simply by increasing the concentration of the reactant until the change in free energy falls below zero. This is called the law of mass action: Adding more reactant (or subtracting some of the product) will often force a reaction. Stubborn reactions can be pushed or pulled.

Spontaneous Reactions

A second law explains completely how spontaneous reactions can provide energy for those that are not spontaneous. It is called the law of the common intermediate and states that reactions can be linked, as far as energy is concerned, by the products of one reaction serving as the reactants of another. Here are two biochemical reactions:

A + B ↔ C + D

X + D ↔ Y + Z

If the first reaction is spontaneous, with a change in free energy less than zero, it produces a substantial amount of C and D. The second reaction would not normally be spontaneous (with its positive change in free energy), but notice that D, the product of the first reaction, is a reactant in the second. When the two reactions are together in the same cell, the buildup of D tends to push the second reaction, reducing the difference in free energy between reactants and products. In other words, the energy produced by the first reaction is being transferred to the second reaction, allowing it to occur. In this case, D is the common intermediate that connects the two.

ATP

In organisms, the sum of all chemical reactions is called metabolism. All the systems of reactions that require energy are called anabolism and those producing it, catabolism. Anabolism and catabolism are tightly linked by common intermediates. A good example of a common intermediate is ATP. Using ATP as an example, it can be seen that the linkage between anabolism and catabolism is a two-way street. ATP is synthesized from adenosine diphosphate (ADP) and phosphate, with the required energy often coming from light (photosynthesis) or from the oxidation of foods (respiration). When ATP is used to provide energy for muscle, for example, it is broken down by hydrolysis to ADP plus phosphate. Thus, the product of catabolism (ATP) is utilized in anabolism, and the products of anabolism (ADP plus phosphate) are utilized in catabolism to regenerate ATP. Thus, the role of ATP is cyclic.

Most common intermediates are phosphate esters such as ATP, although a few are thioesters. It was once thought that such ester bonds were somehow unusual, perhaps containing an abnormally large amount of available free energy. They were often called high-energy bonds. In fact, these ester bonds are not particularly abnormal in their energy; there are many esters with much more energy—compounds that are not important common intermediates. Apparently, the reason that so few compounds have evolved as links between catabolism and anabolism is that their chemical structures are unique in enabling them to participate readily in both.

It appears likely that a very early common intermediate in ancient cells was not ATP but pyrophosphate, which is simply two phosphates hooked together by an ester bond. Apparently, cells evolved the central role for ATP at a later stage. In all these cases, when the energy of a common intermediate is utilized in an anabolic reaction, it is by means of a hydrolysis reaction, the breaking of an ester bond by the addition of water. In many instances, the hydrolysis occurs in more than one step, but it is a hydrolysis, nevertheless, and the free energy that matters in such cases is the free energy of the hydrolysis.

Other Intermediary Compounds

ATP usually gets the most attention, which is proper, because evolution, over the long run, appears to have exhibited the same preference. There are, however, a few other compounds that serve as common intermediates. Several are quite similar to ATP, with a ring-shaped organic part and three phosphates attached in series at one end. The organic parts are a little different, however, and the compounds have different names, with abbreviations such as GTP, UTP, and ITP. These compounds, which are, with ATP, termed nucleoside triphosphates, are readily interchangeable with ATP. For example, ATP can be manufactured from ADP by a phosphate transfer reaction:

ADP + GTP ↔ ATP + GDP

In addition, pyrophosphate, a common intermediate in early cells, transfers energy today in a variety of plant, animal, and bacterial species. In some organisms, pyrophosphate is made (and used) under conditions in which it is, for whatever reason, difficult to make ATP. A few reactions use energy from the hydrolysis of acetyl phosphate, which can be chemically described as a derivative of acetic acid (the active ingredient of vinegar) with a phosphate attached. Also, a number of thioesters, esters with sulfur in place of oxygen, are important common intermediates; they are often large, complicated molecules.

Finally, one may wonder why ATP and similar compounds have as large negative free energies as they do. A complete answer would involve advanced chemistry, but one factor is both important and readily understood. When ATP is hydrolyzed,

ATP + water ↔ ADP + phosphate

both of the products happen to be negatively charged. It is well known that unlike charges attract each other and like charges repel. Therefore, the two products are driven apart from each other, and they are unlikely to react together to produce a back reaction. Thus, the reaction tends to go well in the direction of ADP and phosphate but not the reverse. Another way of saying it is that the reaction is highly spontaneous, or that the reaction exhibits a solidly negative change in free energy, making such compounds good candidates for energy transfer.

Bibliography

Cramer, W. A., and D. B. Knaff. Energy Transduction in Biological Membranes: A Textbook of Bioenergetics. New York: Springer-Verlag, 1990. A complete course, starting with basic principles, emphasizes concepts and information that are central to modern membrane biochemistry, biophysics, and molecular biology. Includes examples, problems with solutions, figures and tables, and extensive references. Intended for advanced study in biochemistry, plant physiology, and biology.

Garby, Lars, and Paul S. Larsen. Bioenergetics: Its Thermodynamic Foundations. New York: Cambridge University Press, 1995. Outlines the biophysical foundation of bioengergetic mechanisms, focusing on the laws of conservation of energy and increase of entropy, thermodynamic equilibrium and nonequilibrium, and energy balance.

Harris, David A. Bioenergetics at a Glance. Cambridge, Mass.: Blackwell Science, 1995. A clear and concise introduction to the study of energy use and conversion in living organisms, with an emphasis on the biochemical aspects of plant science and physiology and on cell biology.

Lehninger, Albert, David L. Nelson, and Michael M. Cox. Principles of Biochemistry. 3d ed. New York: Worth, 2000. A university-level textbook of biochemistry, known for its uncommonly clear presentation. Accessible to a general reader. Chapters specifically address the role of ATP and the ATP-ADP cycle as well as ATP synthesis and utilization. The author was a leader in the field of biological energetics and a long-time student of the place of ATP in the biological world. Particularly useful references.

Mukohata, Yasuo, ed. New Era of Bioenergetics. San Diego: Academic Press, 1991. The results of a Japanese research project on the bioenergetics of cation pumps, redox chains, ATP synthesis, and extremophiles.

Peusner, Leonardo. Concepts in Bioenergetics. Englewood Cliffs, N.J.: Prentice-Hall, 1974. Written by a leading theoretical biologist, covers matters of biological energy and its regulation. The treatment is quite mathematical in places, but clear diagrams and good analogies make it accessible to general readers. Discusses high-energy compounds and coupling between different chemical reactions.