prostaglandins

==== Prostaglandins are molecules that can be found in almost any cell in the body. Although they can be found in many parts of the body, they belong to a classification of hormones that do not circulate, known as eicosaniods. All prostaglandins start out as a fatty acid known as arachadonic acid. Arachadonic acid contains 20 carbons and four double bonds that are not in conjugation.(1,2,3) In 1935, Ulf Svante von Euler-Chelpin was able to isolate prostaglandins from sheep prostate secretions which is how the name prostaglandins came about. Since then we have discovered that prostaglandins are not just found in the prostate gland.(4) ====

==== There are many different types of prostaglandins, each have different names depending on where the double bond and oxygen containing functional groups lie. The name starts off with PG for prostaglandin and another letter and number to help further classify it, such as PGH2, PGE1, PGE2, PGE2α, PGI2, PGF2α, etc. They are all similar in that they each have a five carbon ring and 15 additional carbons in their skeleton and they affect the body in almost the same fashion, but there are some extra functions to each prostaglandin depending on where in the body they are found. Another factor that determines what the function of the PG will be is dependent on which type of g-protein linked receptor it is going to bind to.(5) Some functions include: regulating blood pressure, stimulation of smooth muscle contraction, and pain and inflammatory response.(1,2) Because of this, prostaglandins have become a hot topic in research because of its many functions within the body, especially for the pharmaceutical industry. ====

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==== The chemistry behind the formation of prostaglandins involve multiple reactions. (Figure 1) Since prostaglandins are not made and stored, your body sends a signal for the production of prostaglandins every time a prostaglandin is needed. The start of the synthesis begins with an enzyme, cyclooxygenase (COX), that catalyzes the conversion of arachadonic acid into prostaglandin. You first start with an activated arachidonate. This then undergoes cyclooxygenase activity of COX, also called prostaglandin H2 synthase.(2) Oxygenases catalyze oxidative reactions, allowing for oxygen atoms to directly attach to the molecule to form a new carboxyl group and, in our case, hydroxyl group(s). The first step of this reaction allows us to add oxygen to the arachadonate which than gives us PGG2. The next step is to turn PGG2 into PGH2. This step is done by peroxidase, another way to add molecular oxygen, activity of COX. Through these reactions, we are able to get PGH2 which can then be synthesized into other prostaglandins that our body can use for its various needs.(2) ====

==== Prostaglandins have become a big deal in medicine because as we learn more about how they are produced and function within living bodies; we are able to make new medicines that have less side affects and are more effective in doing their jobs. There are many uses for PG's but PGE's in particular have the most uses because they are the most abundant in the body.(7) An example of this is PGE1 which has been made into an anti-ulcer drug, Cytotec, that works by stopping gastric secretions which is the cause of stomach ulcers.(4,8) PGE1 can also be used for erectile dysfunction, pharmaceutical name is Alprostadil, relax smooth muscles in blood vessels and used to prevent the closure of the ductus arteriosus in infants who have congenital heart disease. It can also be used to induce labor.(4) Another example, PGF₂α properties help to treat glaucoma. PGE₂, which helps with the fever response, also helps to regulate the immune cells, along with other prostaglandins. It can also help to induce labor by softening the cervix and cause uterine contractions. It can also stimulate the bone breaking cell, osteoblasts, to stimulate bone making cells, osteoclasts.(4,9) The negative side is that PGE₂ helps to drive tumor production but once that process is fully understood scientists will be able to create medicines for cancer more effectively.(6) Prostaglandin production can be inhibited by drugs such as Aspirin and any other anti-inflammatory medicine. This works by inhibition of the formation of prostaglandins. Aspirin is able to do this because it inactivates the cycooxygenase activity then acetylates and makes a Ser residue by blocking the active site of the COX enzyme.(2,10) ====

====Prostaglandins may be a very deep subject but worth further pursuing for anyone who is interested in finding new cures or prevention of diseases. Heart attacks and strokes are the leading causes for deaths in industrialized nations and by researching the properties of prostaglandins and how they help prevent platelet formation; we are able to apply this into new therapies that could help save lives. Because of their many properties, they have many possibilities for what they can do to help us understand diseases and abnormalities within living bodies. ====

References
(1) Campbell, M.K., & Farrell, S.O. (2008). Biochemistry. Belmont, CA: Brooks/Cole Cengage Learning. (2) Nelson, D.L., & Cox, M.M. (2005). Principles of Biochemistry. New York, New York: W. H. Freeman and Company. (3) Moore, J., & Langley, R. (2008). Biochemistry For Dummies. Indianapolis, Indiana: Wiley Publishing, Inc. (4) Nicolau, K.C., & Montagnon, T. (2008). Molecules That Changed The World. Federal Republic of Germany: Wiley-VCH. (5) Andreasson, K. (2010). Emerging roles of PGE2 receptors in models of neurological disease. Prostaglandins & Other Lipid Mediators, Volume 91, Issues 3-4, April 2010, Pages 104- 112. doi: doi:10.1016/j.prostaglandins.2009.04.003 (6) Shinichi, K., Fumiaki, K., & Natsuko, K. (2005). Recent Advances in Nonsteroidal Anti- Inflammatory Drugs. Retrieved from http://ai.jsaweb.jp/fulltext/054020209/fig01.html (7) Takayuki, N. (2011). Roles of prostaglandin E2 in the cochlea. Hearing Research, Volume 276, Issues 1-2, June 2011, Pages 27-33. doi: doi:10.1016/j.heares.2011.01.015 (8) Arehart-Treichel, J. (1975). Where Are All Those Prostaglandin Drugs?. Science News, 108(12), 188-190. Retrieved from EBSCOhost. (9) Myong, A., Kraftson, S., & Pohorelsky, J. (2011). The Role of Prostaglandins in Disease and Infection: David Arnoff M.D. Retrieved from http://umurj.org/Interviews/interviews/63- david-aronoff- interview (10) Improving On Aspirin and Vioxx. (2007). Scientific American, 296(1), 86. Retrieved from EBSCOhost. (11) Funk, C. D. (2001). Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology. Science, 294(5548), 1871. Retrieved from EBSCOhost. (12) Ophardt, C.E. (2003). Prostaglandins. Retrieved from http://www.elmhurst.edu/~chm/vchembook/555prostagland.html