The relief or avoidance of pain drives nearly all medical research. By studying how pain is relieved and how the sensation can be avoided, it becomes quite obvious why medical students must spend many hours studying in an organic chemistry classroom. Understanding fundamental chemistry is a key component in determining how to formulate treatments and medicines to alleviate pain. Pain is a sensation that is caused by the release of a chemical called prostaglandin. Prostaglandin stimulates nerve endings in the area of the body experiencing pain, sending an electrical signal to the brain to warn it that the body is in harms way. Some medicines and treatments work to heal or protect the part of the body that is being hurt and injured. Other medicines such as acetylsalicylic acid (C9H8O4), more commonly known as aspirin, alleviate the sensation of pain by inhibiting the formation of prostaglandin. By inhibiting prostaglandin production, aspirin reduces pain, rather than treats it. This action can be understood by looking at the specific shapes of the molecules involved.
Aspirin as a Compound, Not a Pill
The chemical compound of aspirin, C9H8O4, is not very complex. Demonstrated in this image provided by Chemspider acetylsalicylic acid can be shown in a way that can be easily understood. The ring seen in the image is a benzene ring. The carbons form a benzene ring, consisting of 6 carbons with delocalized double bonds. Hydrogen is connected to each of these carbons. However, two of the six carbons in C9H8O4 are not single bonded to hydrogen, but rather to two different functional groups, a carboxylic acid group (seen on the left side), and an ether group (seen on the right). This reference can be used to gain a better understanding of basic functional group purposes and structures. To understand aspirin better as a compound, reference this Pubchem article.
Functional Groups at Work
While carboxylic acid simply comes from a carboxyl group (a combination of a carbonyl and hydroxyl group), it is the ether group that is important to look at. An ether group can be considered a combination of an alcohol (phenol group) and a carboxylic acid. When two compounds of these natures combine, they form ether and water as products. Similarly, the hydrolysis of ether produces alcohol and carboxylic acid. The reaction works in both directions, which is crucial to the usage of aspirin. In the case of aspirin, the ether group is a combination of a simple phenol group (OH) and acetic acid (C2H4O2). When the ether group in aspirin is hydrolyzed, acetic acid is formed, and the aspirin molecule becomes salicylic acid. Uses and the importance of these acids will be discussed later in the blog post. The reaction seen in this image can be further explored through the resources provided by Open University. Interestingly, salicylic acid is one of the earliest natural remedies for pain relief and skin treatment, dating back to 400 BC when the physician Hippocrates unknowingly extracted it from a tree to help relieve pain during childbirth. WebMD provides more information on this compound.
Enzymes and the Importance of Shape
Now that all of that elementary chemistry is taken care of, it is time to cut to the chase. An entire blog post could potentially be written about the formation of the chemical prostaglandin (chemical that causes pain), but for the purpose of this post, it is better to just understand the basics. Prostaglandin is formed from arachidonic acid. This reaction is catalyzed by the enzyme cyclooxygenase (COX). For a basic understanding of how enzymes work, reference this animation from McGraw Hill. In the case of this enzyme-catalyzed reaction, arachidonic acid is the substrate catalyzed in the active site of cyclooxygenase to speed the reaction that forms prostaglandin. The process is shown in the image to the left.
Now it is time to tie all of the ideas together. When aspirin is present, the water present inside of the body hydrolyzes it. This causes the ether group to break up. The result of this process is that the acetal group that once belonged to the aspirin combines with an –OH group (phenol group) present in the enzyme COX. This process is described at acetylating the COX cavity. The outcome of this reaction is quite simply the cavity, or the opening of the active site becoming smaller. As shape is very important to enzymes, this change of shape of the cavity is the magic of aspirin. The enzyme is no longer able to catalyze the formation of prostaglandin, therefore relieving the sensation of pain that should be present. The image to the right shows this idea. The Aspirin Foundation provides a nice summary of all of these ideas, as well as a simple animation to show the timeline of this process.
With a basic understanding of how aspirin prevents the formation of prostaglandin, it is also important to know exactly what would happen if aspirin was not present. Prostaglandins constitute a class of unsaturated fatty acids produced by cells in many parts of the body. They have a variety of physiological effects. For the purpose of this investigation it is most important to note that they are responsible for the activation of the inflammatory response and production of pain and fevers, as they are produced when white blood cells flood damaged tissue areas. More information regarding prostaglandins was compiled here by Elmhurst College. Research on the relationship between prostaglandins and inflammation has been done as well; an example can be found here.
An idea to close this post with is the usage of aspirin as a prevention of heart disease, heart attacks, and even strokes. These ideas all relate back to the inhibition of prostaglandin production. When aspirin is fighting pain, it is simultaneously fighting inflammation associated with heart disease. Prostaglandins not only cause pain, but cause blood clots as well. By inhibiting their synthesis, aspirin prevent blood clots and clogged arteries. WebMD devotes an article on the subject of aspirin therapy and its relationship with the heart for those more interested in the biology of the topic.
For a more in-depth and interactive lesson on the topic of aspirin starting from a beginner’s level of knowledge and working forward, use this source. For a more complex and detailed description of the process, creatingtechnology.org does an excellent job in providing the information.