The Worst Part of Waking up is Ricin in your Cup

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The Worst Part of Waking up is Ricin in your Cup Kelly Borgerding, Jack Craig, Cole Gibbs, Margaret Lichtenfels, Marley Loomis, Rachel Pierce, Melissa Requist, Jack Rosenthal, Rylan Russel, Logan Sankey, Harry Wilson, Cindy Gay Abstract In May 2013, President Barack Obama was sent a letter laced with the toxic extract of the castor bean. This toxin, ricin, is one of the most poisonous naturally occurring Ricin is a protein with two chains, an A chain and a B chain. The A chain is enzymic and causes the toxicity. The B chain is not toxic, but serves as a binding agent and aids the A chain in entering the cell. When a cell is infected with ricin, the B chain binds to receptors on the outside of the cell, causing the cell to take in the protein through endocytosis. The ricin protein is then transported to the endoplasmic reticulum where the A chain then translocates to the cytosol. The active site of the A chain only binds to a specific adenine molecule in the RNA of a ribosome. Once bound, the ricin irreversibly inactivates the ribosome, so the cell cannot produce proteins, eventually leading to cell death. Despite the dangerous implications of ricin, such use in terrorism and warfare, ricin can also be used to treat cancer. The toxic A chain of ricin may be attached to a binding protein that only targets cancer cells. This modified form of ricin, an immunotoxin, would then take effect on and kill cancer cells. A deep understanding of toxins and how they affect a cell can give a toxic killer the opportunity to be a life saver. With more research, immunotoxins may be the most efficient treatment to cancer up to date. substances known, and can cause death in less than a day. Issues arises in how easily castor beans can be obtained and processed to produce a concentrated source of ricin. How Ricin Works Exposure to Ricin can occur in 3 ways: Inhalation, ingestion, and contact with skin and eyes. Symptoms include fever, cough, edema, seizures, kidney failure, and eventually eventually results in death. The B chain is the carrier for the toxic A chain. Ricin targets cells by lodging itself in the cell membrane. The A chain then enters the cell through endocytosis, while the B chain remains in the interstitial fluid ooutside of the cell. Once ricin is in the cytoplasm, the protein chain finds and deactivates ribosomes at a rate of 1500 ribosomes per minute. Since ribosomes are the location of mRNA translation, deactivation of ribosomes prevents protein synthesis, eventually killing the cell. 11 6 Both the A and B chains of the ricin protein are included in this model. An important amino acid in the A chain (shown in green) is serine #265. Serine 265 interacts with Alpha-D-Mannose and is primarily responsible for triggering the death of the cell. The B chain (shown in tan) interacts with receptors on the cell membrane to gain entry for the A chain. Amino acids involved in these reactions are aspartic acid #22 and #25, asparagine #46, lysine #240, glutamine #35, and tyrosine #125, all of which are shown in the model. The struts are not a part of the protein, and are included in the model to provide structural support. Molecular Story Works Cited H. Xuong, R. Hamlin, and J. D. Robertus. "The Three-dimensional Structure of Ricin at 2.8 A." Jbc.org. The Journal of Biological Chemistry, 15 Apr. 1987. Web. 01 May 2014. Berkman, Frank. "Homeland Security: Silk Road Vendor Sent Obama Ricin Letter." Mashable. N.p., 18 Nov. 2013. Web. 01 May 2014. Olsnes, Sjur, and Alexander Pihl. "Different Biological Properties of the Two Constituent Peptide Chains of Ricin a Toxic Protein Inhibiting Protein Synthesis." Biochemistry. ACS Publications, July 1973. Web. 01 May 2014. "Department of Animal Science - Plants Poisonous to Livestock." Cornell University Department of Animal Science. Cornell University, 6 Feb. 2014. Web. 01 May 2014. "Ricin Cancer Therapy Tested." BBC News. BBC, 03 Nov. 2003. Web. 01 May 2014. Endo, Y., and K. Tsurugi. "The RNA N-glycosidase Activity of Ricin A-chain. The Characteristics of the Enzymatic Activity of Ricin A-chain with Ribosomes and with RRNA." Jbc.org. The Journal of Biological Chemistry, 25 June 1988. Web. 01 May 2014. "Ricin Fact Sheet ." Federation of American Scientists. N.p., n.d. Web. 07 May 2014. "Ricin Symptoms, Causes, Treatment - What Are the Signs and Symptoms of Ricin Exposure? - MedicineNet." MedicineNet. N.p., 9 May 2013. Web. 01 May 2014. "Facts About Ricin." CDC. N.p., 9 May 2013. Web. 01 May 2014. Schmitt, Eric, and Thom Shanker. "Qaeda Trying to Harness Toxin For Bombs, U.S. Officials Fear." The New York Times. The New York Times, 12 Aug. 2011. Web. 01 May 2014. Jennifer, Audi, Belson Martin, Patel Manish, Schier Joshua, and Osterloh John. "Ricin Poisoning." JAMA Network. Journal of the American Medical Association, 09 Nov. 2005. Web. 01 May 2014. Goodsell, David. "Ricin." Protein Data Bank. RCSB, May 2013. Web. 01 May 2014. Schnell, R., P. Borchmann, J. O. Staak, J. Schindler, V. Ghetie, E. S. Vitteta, and A. Engert. "Clinical Evaluation of Ricin A-chain Immunotoxins in Patients with Hodgkin?s Lymphoma." Annals of Oncology. Oxford Journals, 2013. Web. 01 May 2014. Lord, J. M., L. M. Roberts, and J. D. Robertus. "Ricin: Structure, Mode of Action, and Some Current Applications." The FASEB Journal. N.p., Feb. 1994. Web. 01 May 2014. Monfort, W., J. E. Villafranca, A. F. Monzingo, S. R. Ernst, B. Katzin, E. Rutenber, N. Welsh, Jennifer. "RICIN: Here's What The Poison Sent To US Officials Can Do." Business Insider. Business Insider, Inc, 17 Apr. 2013. Web. 01 May 2014.