Molecule of the Month: ATP

ATP, or adenosine triphosphate is a molecule which you simply can’t escape if you study science, as so many cellular processes depend on it. The very fibre of our being, our DNA, has aspects of this molecule and allows life to simply flourish.

This wondrous, multi-faceted molecule is the “energy currency” of the cell1, as it provides the “price” which comes along with synthesising and seeing reactions within the body to completion. Every hour, and with every breath, our body is generating this currency so that actions as simple as muscle contraction and essential involuntary processes can take place.

The Wolf of Wall St

When reviewing the overall structure of ATP, the bonds and how they relate to its function, it is not too far off to suggest nature has selected a powerful, chemically harmonious molecule to provide chemical energy. In a helpful sense, the name of ATP can help us construct an idea of what the molecule looks like. Each molecule of ATP is made up of an adenosine nucleotide, a ribose sugar and three phosphate groups. (Figure 1)2

Figure 1- Small, but mighty: The structure of ATP, the three phosphate groups, ribose sugar and the nitrogenous base makes it an ideal molecule for storing chemical energy.

The bonds linking the two phosphate groups to one another are covalent in nature, however they are specifically called phosphoanhydride bonds.3 These bonds are incredibly important as the energy used to fuel biochemical processes and reactions are contained within these bonds. 

Biochemical Battery

In order to release the true power of ATP, the phosphoanhydride bond between the last and adjacent phosphate need to be broken. The chemical process where one of the bonds break, turning ATP into ADP and its associated inorganic phosphate, is mediated by the addition of water. Such reactions, named hydrolysis reactions, are not only limited to ATP, but most biochemicals such as proteins, DNA and carbohydrates.

The difference between ATP and ADP can be thought of like a battery (Figure 2)4 where ATP is the charged molecule, ready to power reactions. After hydrolysis, ADP requires charging via respiration, and the addition of an inorganic phosphate molecule, to return to its charged state.

Figure 2 -Charged for greatness, ATP can undergo hydrolysis reactions to produce ADP which releases a large amount of free energy to link biochemical reactions and processes which would otherwise wouldn’t occur.

Energy is released upon the hydrolysis of ATP for two main reasons. First, there is a great amount of repulsion between the phosphate molecules as they contain a negative charge and are “forced” to be next to one another1. Upon hydrolysis, this repulsion is relieved. Secondly, the products of this reaction, ADP and Pi exist on a lower energy state that the reactants, ATP and water.

Glucose Guardian

ATP is one of the many molecules that makes the process of simply existing, respiration, possible. Respirations is a complex, multi-step process mediated by various organs and the reactions which make this possible is mediated and moreover, possible due to ATP.

However, to really exemplify the purchasing power, as I like to call it, that ATP has we can look at the conversion of a sugar molecule, glucose, into pyruvate.

Just like you cannot make something as complex as cake directly from egg alone, glucose undergoes incremental changes via the use of various “ingredients” to produce pyruvate. The outcome of might not be as tasty as cake however, pyruvate is an important intermediate molecule. Pyruvate has the ability to go into the later stages of respiration and can concentrate itself into fatty acids. Where pyruvate is destined is dependent on the bodies needs and requirements and is adjusted accordingly.

Of the many steps required to produce pyruvate from glucose, the first reaction actually requires the “exchange power” that comes with the hydrolysis of ATP. The first step of this reaction is the conversion of glucose to glucose-6-phosphate (Figure 3)5

Figure 3 – Coupled Up: The breakage of bonds and their reformation, especially for the formation of glucose-6-phosphate, costs energy which the hydrolysis of ATP readily provides.

Although the reaction is mediated by the enzyme hexokinase, the hydrolysis of ATP is an integral part of the process for producing glucose-6-phosphate.

ATP has a twofold purpose in this case, it is a phosphate donor but more importantly, provides the energy required to form glucose-6-phosphate. Without ATP, the conversion of glucose-6-phosphate from glucose would not take place as it deemed “energetically unfavourable” and cannot progress towards completion 6. A process known as reaction coupling, links the hydrolysis of ATP to the formation of glucose-6-phosphate.

The formation of glucose-6-phosphate is an incredibly important biochemical reaction as it both traps glucose, in the form of glucose-6-phosphate, within the cell membrane and the phosphoryl group destabilises glucose, facilitating its further breakdown5.

ATP has been described as approaching “perfection” as the cellular currency the body uses between the energy stored within the bonds and the way in which the hydrolysis reactions are coupled with unfavorable reactions 7. However, there is an emerging consensus and evidence that extracellular (outside of the cell) ATP plays a role in the immune system responses and wider signalling8,9,10.

Nevertheless, the exchange power the ATP utilises has been around since the dawn of biological evolution, right up to the present day presenting the powerful driving force of nature itself 11

Note: “Glucose-6-phosphate” simply means the phosphate molecule is attached to carbon number 6 of the glucose molecule. It is a way in which students and scientists around the world can identify where the modification can take place, and to construct a picture of what the molecule looks like.

References:

1.         Dunn, J. & Grider, M. H. Physiology, Adenosine Triphosphate (ATP). in StatPearls (StatPearls Publishing, 2020).

2.         ATP structure + function. Loreto Sixth Form College A level Biology http://loretocollegebiology.weebly.com/atp-structure–function.html.

3.         Alberts, B. et al. The Chemical Components of a Cell. Mol. Biol. Cell 4th Ed. (2002).

4.         Energy Conversions | BioNinja. https://ib.bioninja.com.au/higher-level/topic-8-metabolism-cell/untitled/energy-conversions.html.

5.         Berg, J. M., Tymoczko, J. L. & Stryer, L. Glycolysis Is an Energy-Conversion Pathway in Many Organisms. Biochem. 5th Ed. (2002).

6.         Cooper, G. M. Metabolic Energy. Cell Mol. Approach 2nd Ed. (2000).

7.         Walsh, C. T., Tu, B. P. & Tang, Y. Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism. Chem. Rev. 118, 1460–1494 (2018).

8.         Faas, M. M., Sáez, T. & de Vos, P. Extracellular ATP and adenosine: The Yin and Yang in immune responses? Mol. Aspects Med. 55, 9–19 (2017).

9.         Trautmann, A. Extracellular ATP in the Immune System: More Than Just a “Danger Signal”. Sci. Signal. 2, pe6–pe6 (2009).

10.       KHAKH, B. S. & BURNSTOCK, G. The Double Life of ATP. The Scientific American 84–92 (2009).

11.       Plattner, H. & Verkhratsky, A. Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling. Philos. Trans. R. Soc. B Biol. Sci. 371, 20150419 (2016).

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