"What is Chemistry Good For?"

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Please respond before 5 AM, Monday, November 27th, 2000.

Chemistry is Good for Designing Drugs

When it all comes down to it, there is nothing more important to us than our blood. If we lose it, we die. Our body has developed a very complex mechanism for creating our blood so that we can live and stay healthy. The composition of this vital fluid is carefully controlled in terms of pH (acidity), cholesterol level, sugar level, oxygen carriers and many other factors. It even contains parts of out natural defense mechanism against infection. Entire libraries could be filled with what we have learned about blood and we still are barely scratching the surface of what we will learn in the near future. One very important topic that is quite well understood is the clotting of blood.

When our blood vessels develop a leak, it is very important that the leak be sealed. There are two very important mechanisms for triggering the formation of blood clots. If blood contacts a foreign or abnormal surface, then a clot is triggered. If there is a trauma that does damage to tissues, extracts from the tissues, especially brain tissue, will trigger clot formation. Either triggering pathway leads to a common pathway for the formation of the clot. The material that is synthesized by our bodies to form the clot is called fibrin. It is formed when fibrinogen is converted to fibrin by thrombin. Our bodies synthesize prothrombin, an active precursor to thrombin, which can then be activated by the cleavage of a peptide bond. Many of the participants in the clotting pathways are enzymes or other proteins. Others are smaller chemicals.

Vitamin K is important for the synthesis of prothrombins and other clotting factors. Because of this, other chemicals that have similar structures and shapes to Vitamin K can interfere with the process of clotting. They take the place of Vitamin K in an enzyme (like the wrong key in a lock), but canŐt perform the task of Vitamin K. For this reason they are called antagonists of Vitamin K. Without the right clotting factors, our blood canŐt clot and wounds do not heal. Something as simple as a nosebleed would be fatal for us if our blood was unable to form clots. Cattle that ingested spoiled sweet clover developed a fatal hemoraghic disease because of a Vitamin K antagonist called dicoumarol in that type of hay. Other similar anticoagulant molecules such as warfarin are used as rat poisons. You can see the similarities between warfarin and Vitamin K by looking at their molecular structures. Drug developers constantly study the structures of biological molecules so that they can synthesize molecules that can either act in a similar way to the natural systems or interfere with their function.

Even though the biochemical engineering of Mother Nature is incredible, many people experience problems that can be life threatening. A genetic defect can prevent the blood of some people from clotting. This type of hemophilia is very famous because it afflicted the royal families of Europe during the 19thcentury. Queen Victoria of England carried the faulty gene and its transmission to her progeny resulted in early deaths for 8 of her male offspring within 4 generations. Because he did not understand molecular and genetic diseases, the famous "miracle healer" Rasputin was powerless to help the Royal families. Here is a geneology of the royal family that indicates who suffered from hemophilia. Like the gene for baldness, the gene for hemophilia carried on the X chromosome and is recessive. Women carry the gene, but are seldom afflicted with the condition.

If the lack of clotting ability is such a life-threatening problem, then why do doctors prescribe anticoagulants to their patients? Excessive clotting can be dangerous because blood clots can interfere with normal blood flow if not confined to areas of injury. Thus, any patient who has a blood clot is given anticoagulants. Although they will not dissolve existing clots, they will prevent clots from enlarging and will prevent new clots from forming. Anticoagulants are also given to people who have artificial heart valves or who are undergoing some surgeries. The presence of foreign materials can trigger the clotting mechanism. Preservation of life requires a very delicate balance to insure that clotting occurs when needed but does not occur when it might be problematic. Sometimes this balance must be preserved by chemical means.

And here are a few good links to get you started.

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Research Questions (You will receive 1 point of extra credit for each correct answer up to a total of two points for this assignment)

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    These questions can be answered by exploring the links provided to you above.
  1. What is the name of the course/subject that deals specifically with the study of blood?
  2. Name 5 serious side effects for warfarin.
  3. List 5 medicines that warfarin interacts with.
  4. How does coumadin affect blood clotting? Give specific cascade events.

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